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Background : Patients with rheumatoid arthritis ( RA ) with an inadequate response to TNF antagonists ( aTNFs ) may switch to an alternative aTNF or start treatment from a different class of drugs , such as rituximab ( RTX ) . It remains unclear in which clinical setting s these therapeutic strategies offer most benefit . Objective : To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients . Methods : A prospect i ve cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF , nested within the Swiss RA registry ( SCQM-RA ) was carried out . The primary outcome , longitudinal improvement in 28-joint count Disease Activity Score ( DAS28 ) , was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders . Results : Of the 318 patients with RA included ; 155 received RTX and 163 received an alternative aTNF . The relative benefit of RTX varied with the type of prior aTNF failure : when the motive for switching was ineffectiveness to previous aTNFs , the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF ( p = 0.03 ; at 6 months , −1.34 ( 95 % CI −1.54 to −1.15 ) vs −0.93 ( 95 % CI −1.28 to −0.59 ) , respectively ) . When the motive for switching was other causes , the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs ( p = 0.40 ) . These results were not significantly modified by the number of previous aTNF failures , the type of aTNF switches , or the presence of co-treatment with a disease-modifying antirheumatic drug . Conclusion : This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF Objective To explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naïve rheumatoid arthritis patients . Methods Consecutive biologic-naïve patients with rheumatoid arthritis initiating infliximab ( n = 57 ) or tocilizumab ( n = 70 ) treatment were included in our prospect i ve cohort study . Our cohort started in February 2010 , and the patients observed for at least 1 year as of April 2013 were analysed . We assessed baseline variables including patients ' characteristics ( age , sex , disease duration , prednisolone dose , methotrexate dose , other disease-modifying antirheumatic drug use , Clinical Disease Activity Index [ CDAI ] ) and serum biomarker levels ( C-reactive protein , immunoglobulin M-rheumatoid factor , anti-cyclic citrullinated protein/peptide antibodies , interferon-γ , interleukin (IL)-1β , IL-2 , IL-6 , IL-8 , IL-10 , IL-17 , tumor necrosis factor-α , soluble intercellular adhesion molecule-1 , bone alkaline phosphatase , osteonectin , osteopontin ) to extract factors associated with clinical remission ( CDAI≤2.8 ) at 1 year using univariate analyses , and the extracted factors were entered into a multivariate logistic regression model . Similar analyses were also performed for Simplified Disease Activity Index ( SDAI ) remission ( ≤3.3 ) and Disease Activity Score with 28 joint counts , erythrocyte sedimentation rate ( DAS28-ESR ) remission ( < 2.6 ) . Results There were no significant differences in the baseline characteristics except for methotrexate use between the groups . In the multivariate analyses , the low baseline osteopontin levels ( OR 0.9145 , 95 % CI 0.8399–0.9857 ) were identified as predictors of CDAI remission in the tocilizumab group , whereas no predictors of CDAI remission were found in the infliximab group . Similar results were obtained when using SDAI and DAS28-ESR remission criteria . Conclusion Baseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic-naïve patients with rheumatoid arthritis . Our prediction model provided insights into how to optimize the choice of biologics and warrants external validation in other cohorts Background / objective Progression of joint damage is linked to disease activity . This link is dissociated upon treatment with tumour necrosis factor (TNF)- or IL-6-inhibitors plus methotrexate ( MTX ) . It is hitherto unknown if this may also be true for therapies targeting B-cells . We thus evaluated if rituximab ( RTX ) therapy inhibits joint damage irrespective of its effects on disease activity . Methods We used a r and om 90 % sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis ( RA ) receiving MTX ( n=188 ) or MTX+RTX 1000 mg ( n=204 ) . Patients were divided into low , moderate and high disease activity at one year of treatment by simplified disease activity index ( low disease activity ( LDA ) , moderate disease activity ( MDA ) , high disease activity ( HDA ) ) , or by swollen joint count ( SJC ) or C reactive protein ( CRP ) tertiles . Progression of damage by the Genant modified total Sharp score ( TGSS ) was compared between therapies ( Kruskal-Wallis , Wilcoxon tests ) for each of these subgroups . Results In patients treated with MTX , 1-year progression of TGSS In LDA , MDA and HDA was 0.40±0.88 , 1.04±1.73 , and 1.31±3.02 , respectively . In contrast , on RTX+MTX  , TGSS progression was 0.38±1.07 , 0.39±1.28 , and −0.05±0.44 , respectively ( for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group : p=0.003 and p=0.05 , respectively ) . Additional analyses ( tertiles of SJC , CRP , and matching for disease activity ) confirmed the primary analysis . Conclusions In early RA , progression of joint damage increases with increasing disease activity on MTX . RTX plus MTX retards damage independently of its effects on disease activity , since even in HDA destruction is halted , contrasting MTX monotherapy . This indicates that beyond cytokine blockade ( TNF- and IL-6 inhibitors ) , also cell-directed therapy ( anti-CD20 antibody ) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage OBJECTIVES To describe the changes in functional ability ( FA ) taking place over 5 yr in patients with rheumatoid arthritis ( RA ) starting disease-modifying anti-rheumatic drug ( DMARD ) therapy  , to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment . METHODS Three hundred and sixty-six patients with active RA were studied as part of a 5-yr r and omized controlled study of DMARD therapy . FA was assessed by  Health Assessment Question naire  ( HAQ )  score every 6 months . Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr . The independent variables used were age , sex , visual analogue scale ( VAS ) pain , Ritchie articular index , C-reactive protein ( CRP ) , Larsen score and log-transformed morning stiffness ( EMS ) . RESULTS Mean HAQ score was 1.64 at baseline , improved by 21 % at 1 yr and gradually returned towards baseline levels by 5 yr . At baseline only 34 % of variance in HAQ score could be explained ; the most significant explanatory variables were the Ritchie articular index and CRP . At 5 yr the variance explained was 60 % . The Ritchie articular index remained the strongest factor followed by VAS pain , log(10 ) EMS and Larsen score . CONCLUSIONS Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr . The most consistent factor affecting function was joint tenderness . Global pain and duration of EMS were of lesser importance . Disease activity measures such as the CRP exerted an influence in the earlier , more active stages of disease : radiographic damage assumed greater importance as the arthritis progressed OBJECTIVE To investigate whether determination of a set of laboratory markers at baseline provides prognostic information on joint damage in h and s and feet in rheumatoid arthritis . METHODS 183 patients with early rheumatoid arthritis included in a prospect i ve study were examined . Radiographic changes in h and s and feet at 5 and 10 years after inclusion were evaluated ( Larsen ) . The markers analysed were : erythrocyte sedimentation rate ( ESR ) ; HLA-DRB alleles typed by restriction fragment length polymorphism ; and C reactive protein , cartilage oligomeric matrix protein ( COMP ) , rheumatoid factor ( RF ) ( IgG , IgA , and IgM subtypes ) , antibodies against cyclic citrullinated peptide ( anti-CCP ) , and antibodies against interleukin 1alpha ( anti-IL1alpha ) , analysed by immunoassays . Multiple linear regression with backward elimination was used to determine the prognostic value of the variables . RESULTS 117/176 patients were positive for IgG RF , 138/176 for IgA RF , 139/176 for IgM RF , 140/176 for anti-CCP , and 40/182 for anti-IL1alpha . After five years , ESR , the presence of IgA RF , serum COMP , and the presence of anti-CCP were significantly associated with more severe joint damage , and the presence of anti-IL1alpha with less severe joint damage . Baseline C reactive protein and anti-CCP predicted radiographic outcome after 10 years . A stronger prediction was obtained by combining the prognostic factors . CONCLUSIONS Early determination of anti-CCP , IgA RF , anti-IL-1alpha , ESR , C reactive protein , and COMP predicted the development of joint damage in h and s and feet in this cohort . A combination of these measures reflecting different aspects of the disease process should be useful for evaluating prognosis in individual patients with early rheumatoid arthritis OBJECTIVES To predict the long-term outcome of rheumatoid arthritis ( RA ) with respect to radiographic damage , disability , and disease course using baseline variables , and to construct decision trees identifying patients on an individual level at the extremes of the outcome spectrum of these 3 dimensions . METHODS The 12-year outcome of 112 female RA patients from a prospect i ve inception cohort was assessed by measuring the tertiles of radiographic damage ( measured by the modified Sharp/van der Heijde method , SHS ) , disability ( measured by the Health Assessment Question naire , HAQ ) , and severe disease course as defined by patients with either the 33 % highest cumulative disease activity ( area under the curve of all observed disease activity scores ) or the highest tertile of radiographic damage . Patients in the lowest ( mild ) and highest tertile ( severe ) of each outcome measure were identified . All baseline parameters known to be associated with each outcome ( demographic and socioeconomic parameters ; disease duration ; disease activity measures ; laboratory measures including rheumatoid factor , HLA typing , percentage agalactosyl IgG , functional and radiographic measures ) were entered into cross-vali date d stepwise logistic regression models to find the best predictive combination of baseline parameters for each of the outcomes . Using the results of the logistic regression models , simple decision trees were constructed to categorize patients at an individual level in a particular prognostic group . RESULTS After 12 years , the lowest and highest tertiles were , respectively , 42.3 and 189 for the SHS and 0.37 and 1.25 for the HAQ . Fifty-five patients had a severe disease course . Mild and severe radiographic damage could be predicted with an accuracy of 90 % and 85 % , respectively . Mild and severe HAQ could be predicted with an accuracy of 90 % and 84 % , respectively , and severe disease course with an accuracy of 81 % . The baseline variables found to be predictive of all 3 outcome measures were very similar and consisted of combinations of the following baseline parameters : swollen joint count ( SJC ) , Ritchie score , rheumatoid factor ( RF ) , the presence of erosions , and the HAQ score . Additional knowledge of the HLA typing hardly improved the accuracy of the prediction . To predict outcome at the individual level , simple decision trees were constructed using the RF , HAQ , SJC , and presence of erosions at baseline . CONCLUSION The present study shows that prediction of outcome in long-term RA is possible and can be done using widely available baseline parameters Seventy two patients with classical or definite rheumatoid arthritis ( RA ) were r and omly allocated to receive gold or D-penicillamine therapy ( DPA ) in a prospect i ve study design ed to evaluate whether it is possible to predict which patients will show radiological progression despite therapy . Forty five patients completed 12 months ' treatment . There were no significant demographic or clinical differences between them and the 27 drop outs . Twenty of the 45 patients showed no radiological progression between six and 12 months . These patients had less severe initial radiological damage , lower levels of serum aspartate transaminase ( serum AST ) and lactic dehydrogenase ( LDH ) , but higher levels of serum cholesterol . Twenty five patients did show progression during the six to 12 month period . This group included all the men with nodules . Of the 43 pretreatment clinical and laboratory variables examined , however , the majority failed to predict whether or not progression would subsequently occur . This included the acute phase response and seropositivity Background Age , C-Reactive Protein ( CRP ) and autoantibodies ( Abs ) are associated with worse prognosis in patients with recent-onset inflammatory polyarthritis ( EPA ) . Serum 14 - 3 - 3η protein is a joint-derived biomarker that up-regulates cytokines and enzymes that perpetuate local and systemic inflammation and may contribute to joint damage . Our objective was to evaluate , over a 5-year prospect i ve period of observation , the additional prognostic potential of serum 14 - 3 - 3η protein in EPA patients . Methods Clinical variables , serum and radiographs  ( scored according to the Sharp/van der Heijde ( SvH ) method ) were collected serially . Relationships between serum 14 - 3 - 3η protein and other biomarkers were computed with Spearman correlations . Outcomes were Simple Disease Activity Index ( SDAI ) scores and joint damage progression : ΔSvH for SvH score and ΔErosion for its Erosive component . The additional predictive contribution of 14 - 3 - 3η was defined using generalized estimating equations ( GEE ) and generalized linear mixed models ( GLMM ) . Results Among 331 patients , baseline 14 - 3 - 3η was ≥0.19 and ≥0.50 ng/ml in 153 ( 46.2 % ) and 119 ( 36.0 % ) , respectively ; CRP was > 8.0 mg/L in 207 ( 62.5 % ) , and at least one Ab ( Rheumatoid Factor , anti-CCP2 or anti-Sa/citrullinated vimentin ) was positive in 170 ( 51.5 % ) . Elevated 14 - 3 - 3η levels moderately correlated with positive Abs , but not with elevated CRP . Baseline 14 - 3 - 3η ≥0.19 ng/ml was associated with more radiographic progression over 5 years . The optimal levels of baseline 14 - 3 - 3η to predict radiographic progression was defined by ROC curves at 0.50 ng/ml . Levels of 14 - 3 - 3η ≥0.50 ng/ml at baseline were associated with lower likelihoods of ever reaching SDAI remission ( RR 0.79 ( 95 % CI 0.64–0.98 ) , p = 0.03 ) and higher subsequent progression of Total and Erosion SvH scores . Elevated levels of 14 - 3 - 3η during follow-up also predicted higher subsequent progression , even in patients in SDAI remission . Decreases of 14 - 3 - 3η levels by at least 0.76 ng/ml and reversion to negative during follow-up associated with less subsequent radiographic progression . In multivariate models , elevated 14 - 3 - 3η interacted with positive Abs , elevated CRP and older age to predict subsequent radiographic progression . Conclusions Levels of 14 - 3 - 3η protein ≥0.50 ng/ml predict poorer clinical and radiographic outcomes in EPA , both at baseline and after initiation of treatment , even in SDAI remitters . 14 - 3 - 3η , CRP , age and Abs represent independent predictors of subsequent joint damage . Trial registration Clinical Trials.gov ID : NCT00512239 . Registered August 6 , 2007 Background Treatment with tumour necrosis factor inhibitors ( TNF-i ) plus methotrexate ( MTX ) , but not MTX monotherapy alone , inhibits joint damage progression even at higher levels of disease activity . Such disassociation of disease activity and structural damage has not been shown for biological agents other than TNF-i . Objectives To evaluate whether interleukin 6 ( IL-6 ) inhibition with tocilizumab ( TCZ ) interferes with joint destruction beyond its effects on disease activity . Methods A r and om 90 % sample of data from the ( The Tocilizumab Safety and the Prevention of Structural Joint Damage Study ) LITHEtrial on active rheumatoid arthritis ( RA ) despite MTX was used , which compared addition of placebo ( n=117 ) with addition of TCZ ( n=414 ) every 4 weeks . Baseline and 1-year values of clinical and serological variables were correlated with changes to 1 year of the total Genant-modified Sharp score ( TGSS ) using a Spearman test , and the progression of TGSS , erosion and joint space narrowing ( JSN ) scores in groups with low and high disease activity were compared for placebo and TCZ ( Kruskal – Wallis ) . Results Baseline variables were similar among the groups . Change of TGSS was lower in patients receiving TCZ than placebo ( TCZ : 0.29±0.96 ; placebo : 0.90±1.92 ; p=0.0007 ) . In patients  receiving placebo , the correlation with TGSS change was significant for baseline scores of the simplified disease activity index ( SDAI ; r=0.18 , p=0.047 ) and swollen joint count 28 ( r=0.22 , p=0.019 ) , with similar trends for C-reactive protein . Similar correlations were seen for SDAI , clinical disease activity index , disease activity score 28 at 1 year with x-ray change during that year ( r=0.26–0.28 , p=0.002–0.006 ) . In contrast , none of the baseline or 1-year variables showed significant correlation with x-ray changes in patients receiving TCZ+MTX , suggesting a disassociation of the link between disease activity and damage by TCZ . Finally , for patients in remission or with low disease activity , progression of TGSS , erosion and JSN was similar among treatment groups ( TGSS : placebo , 0.4±1.1 ; TCZ , 0.2±0.7 ; p = NS ) , while for patients with moderate or high disease activity placebo-treated patients progression was significantly greater ( TGSS : 1.2±2.2 vs 0.4±1.2 ; p=0.0009 ) . Conclusions IL-6 inhibition with TCZ plus MTX  retards joint damage progression independently of its impact on disease activity . Similar effects have hitherto been reported only for TNF-i . This indicates that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable Background To assess whether , in the real world of three early arthritis clinics , early referral could allow the best outcome , ie , remission , to be reached , and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa . Methods 1795 patients with early arthritis ( symptom duration ≤12 months ) were entered into a prospect i ve follow-up study . 711 patients ( 39.6 % ) were diagnosed with rheumatoid arthritis ( RA ) . Each RA patient was treated according to the local algorithm , in three tertiary referral centres ( representing a small province , a medium sized province and a metropolitan area , respectively ) . Remission , defined using the disease activity score in 28 joints ( DAS28 < 2.6 ) and American College of Rheumatology ( ACR ) criteria , was the major outcome evaluated at the 12-month follow-up . Results DAS28 remission was achieved in 34.3 % ( range 19.5–49 % ) of RA patients and ACR remission in 15.2 % ( range 8.5–20.6 % ) . At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome : being in very early rheumatoid arthritis ( VERA ; less than 12 weeks symptom duration at the time of first treatment ) and being on disease-modifying antirheumatic drugs ( DMARD ) within 3 months from disease onset . Among RA patients in remission , only 10 % of VERA subjects received an anti-TNF blocker compared with 32.2 % of non-VERA patients ( p=0.002 , OR 0.23 , 95 % CI 0.09 to 0.64 ) . Conclusions In a real-world setting , the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome , ie , remission of RA . Moreover , VERA represents a window of opportunity in terms of cost saving We performed a Monte Carlo study to evaluate the effect of the number of events per variable ( EPV ) analyzed in logistic regression analysis . The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality ; the number of events per predictive variable was ( 252/7 =) 36 for the full sample . For the simulations , at values of EPV = 2 , 5 , 10 , 15 , 20 , and 25 , we r and omly generated 500 sample s of the 673 patients , chosen with replacement , according to a logistic model derived from the full sample . Simulation results for the regression coefficients for each variable in each group of 500 sample s were compared for bias , precision , and significance testing against the results of the model fitted to the original sample . For EPV values of 10 or greater , no major problems occurred . For EPV values less than 10 , however , the regression coefficients were biased in both positive and negative directions ; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients ; the 90 % confidence limits about the estimated values did not have proper coverage ; the Wald statistic was conservative under the null hypothesis ; and paradoxical associations ( significance in the wrong direction ) were increased . Although other factors ( such as the total number of events , or sample size ) may influence the validity of the logistic model , our findings indicate that low EPV can lead to major problems Objective : Personalized treatment depends on the treatment goals . Current prediction models to guide initial treatment choices focus on radiological damage progression . However , for some patients this outcome is less relevant , whereas short-term functional ability is relevant to all . Do these various treatment goals share the same predictors ? Methods : Data for 497 patients from the Dutch Beh and el Strategieen ( BeSt ) study of treatment strategies for early rheumatoid arthritis ( RA ) , r and omized to initial monotherapy or combination therapy , were used . Predictors of short-term functional disability [ Health Assessment Question naire ( HAQ ) score ≥ 1 after 3 months of treatment ] were identified with logistic regression analyses . Predicted risks of a HAQ score ≥ 1 were determined for each treatment group and for each sub population . Results : At baseline , 76 % of patients had a HAQ score ≥ 1 ( mean 1.7 ± 0.5 ) . After 3 months of treatment this score was achieved by 40 % ( mean HAQ score 1.5 ± 0.5 ) . Baseline HAQ score , pain , the Ritchie Articular Index ( RAI ) , and treatment group were significant independent predictors for a HAQ score ≥ 1 ; the presence of rheumatoid factor ( RF ) , anti-cyclic citrullinated peptide ( anti-CCP ) antibodies , and baseline radiological damage were not . With cut-offs of 35 % and 60 % , the risk of a HAQ score ≥ 1 was high for 47 % and low for 20 % of the patients treated with initial monotherapy . Risks were markedly reduced in the combination therapy groups , also in unfavourable risk profiles . Conclusion : In recent-onset active RA  , baseline HAQ score , pain , and initial treatment are predictors for a HAQ score ≥ 1 after 3 months . Known predictors of radiological damage were not predictive of short-term functional disability . The choice of the best initial treatment thus depends on the relevance of various outcome measures for an individual patient The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis ( RA ) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs ( DMARDs ) and very low doses of oral glucocorticoids .  One hundred and five patients ( 81 % female ) with early RA ( disease duration < 2 years ) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy , together with methylprednisolone ( 4 mg/day ) , were followed up for 2 years . The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method . Clinical , biological , immunogenetic , and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up . Radiographic progression ( increase of four or more units in the Larsen score ) was observed in 32 % of patients after 2 years of follow-up . The percentage of erosive disease increased from 18.3 % at baseline to 28.9 % at 12 months and 44.6 % at 24 months , in spite of a significant improvement in disease activity . New erosions appeared in 33 % of patients after 2 years . Several baseline parameters were associated with radiographic progression in the univariate analysis : shared epitope ( SE ) homozygozity , HLA-DRB*04 alleles , female gender , hemoglobin , erythrocyte sedimentation rate , and anticyclic citrullinated peptide antibodies ( anti-CCP ) . In the multivariate analysis , female gender [ odds ratio ( OR ) 5.5 , 95 % confidence interval ( CI ) : 1.1–28.2 , p = 0.04 ] , DRB1 * 04 alleles ( OR 3.1 , 95 % CI 1.1–9 , p = 0.03 ) and , marginally , anti-CCP antibodies ( OR 3.6 , 95 % CI 0.9–14.5 , p = 0.06 ) , were associated with progression . Female patients with both DRB1 * 04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression . The presence , but not the titer , of anti-CCP antibodies predicted progression . The positive predictive value of the multivariate model for progression was only 53.9 % whereas the negative predictive value was 80.3 % . In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids , radiographic progression was observed in one third of patients after 2 years . Female gender , DRB1 * 04 alleles ( rather than the SE ) , and the presence of anti-CCP antibodies at baseline ( independently of the titer ) were the most important predictors of progression . The utility of these parameters in clinical practice is limited by their relatively low positive predictive value Objectives To study clinical predictors for radiographic progression after 1 year in an early rheumatoid arthritis ( RA ) trial . Methods In the SWEFOT trial population , disease modifying antirheumatic drug ( DMARD ) naïve RA patients started methotrexate ; 3-month responders ( DAS28 < 3.2 ) continued ( n=147 ) , while non-responders were r and omised to addition of sulfasalazine+hydroxychloroquine ( n=130 ) or infliximab ( n=128 ) . X-rays were scored by the Sharp-van der Hejde score ( SHS ) method and radiographic progression was defined as a ≥5 increase after 1 year . Potential baseline predictors of radiographic progression were tested using multivariable logistic regression , adjusted for potential confounders . Results 79 of 311 patients with available radiographs at baseline and follow-up  had radiographic progression . The following baseline parameters were independent predictors of radiographic progression at 1 year : baseline erosions ( adjusted OR=2.29 , 95 % CI 1.24 to 4.24 ) , erythrocyte sedimentation rate ( adjusted OR per tertile increase=1.72 , 95 % CI 1.12 to 2.65 ) and C-reactive protein ( adjusted OR per tertile increase=1.52 , 95 % CI 1.03 to 2.26 ) . Current smoking was an independent predictor of radiographic progression ( adjusted OR=2.17 , 95 % CI 1.06 to 4.45 ) . These results remained after further adjustment for treatment strategy . Three-dimensional matrix including current smoking status , erosions and C-reactive protein tertiles showed a 12–63 % risk gradient from patients carrying none compared with all predictors . Rheumatoid factor (RF)/anti-cyclic citrullinated peptide ( anti-CCP ) positivity did not significantly predict radiographic progression using SHS increase ≥5 as cut-off . In a secondary exploratory analysis using cut-off > 1 , both RF and anti-CCP positivity were significant predictors in the unadjusted , but not the adjusted analyses . The other parameters also remained significant using this lower cut-off . Conclusions In addition to previously described predictors , we identified smoking as a strong independent risk factor for radiographic progression in early RA . Trial registration number NCT00764725 Tumor necrosis factor ( TNF ) inhibitors have produced improvements in clinical , radiographic , and functional outcomes in rheumatoid arthritis ( RA ) patients . However , it remains unclear whether factors affecting physical functions remain following TNF therapy . The objective of our study was to assess factors affecting improvement of physical functions and to shed light on relations to disease activity and structural changes in patients with RA treated with etanercept .  The study enrolled 208 patients , all of whose composite measures regarding clinical , radiographic , and functional estimation both at 0 and 52 weeks after etanercept therapy were completed . Mean disease duration of 208 patients was 9.6 years , mean Disease Activity Score for 28 joints ( DAS28 ) was 5.4 , and mean van der Heijde modified total Sharp score ( mTSS ) was 94.6 . Mean Health Assessment Question naire Disability Index ( HAQ-DI ) improved from 1.4 at 0 weeks to 1.0 at 52 weeks after etanercept therapy , a 31 % reduction , which was much less than changes in DAS28 and mTSS . By multivariate analysis , HAQ-DI and mTSS at baseline were significantly correlated HAQ remission . Median HAQ-DI improved in 100 versus 20 % of the HAQ-DI ≤0.6 versus ≥2.0 groups , respectively . The mTSS cutoff point at baseline to obtain HAQ remission was 55.5 . During etanercept treatment in the mTSS < 55.5 versus > 55.5 groups , median HAQ-DI improved in 70 versus 39 % ; remission was achieved in 59 versus 33 % ; and there was no improvement in14 versus 30 % , respectively . HAQ-DI improvement was significantly correlated with that of DAS28 but not of mTSS . In conclusion , higher HAQ and mTSS at baseline inhibits HAQ-DI improvement within 1 year of etanercept treatment , and the cutoff point necessary for mTSS to improve physical functions in patients with RA was 55.5 The  efficacy and safety of golimumab + methotrexate ( MTX ) were evaluated in Chinese patients with active rheumatoid arthritis ( RA ) despite MTX therapy Objective To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different c and i date autoantigens and therapeutic outcome in early rheumatoid arthritis ( RA ) . Methods Baseline and 3-month serum sample s from 316 patients with early RA enrolled in the Swedish Farmacotherapy ( SWEFOT ) trial were analysed for antibodies against cyclic citrullinated peptides ( CCP ) and citrullinated peptides derived from vimentin ( cVim ) , fibrinogen ( cFib ) and α-enolase ( CEP-1 ) . At 3-month follow-up , methotrexate monotherapy-inadequate responders were r and omised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab . In these patients , anticitrullinated peptide antibodies ( ACPA ) were also assessed at 12 and 24 months . The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression . Results During the 2-year follow-up , the proportion of patients testing positive declined significantly regarding antibodies to cVim , cFib and CEP-1 , while anti-CCP antibody occurrence remained stable over time . Turning anti-cVim antibody negative was most common , and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive . Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy , with no significant relation to treatment regimen or radiographic progression . Conclusions The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities , and early disappearance of anti-cVim antibodies associated with better radiological outcome . Thus , these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA . Trial registration number WHO data base at the Karolinska institute : CT20080004 ; and clinical trials.gov : NCT00764725 Individual participant time-to-event data from multiple prospect i ve epidemiologic studies  enable detailed investigation into the predictive ability of risk models . Here we address the challenges in appropriately combining such information across studies . Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration , a collation of individual data from multiple prospect i ve studies with an average follow-up duration of 9.8 years ( date s varied ) . We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination , Harrell 's concordance index , and Royston 's discrimination measure within each study ; we then combine the estimates across studies using a weighted meta- analysis . Various weighting approaches are compared and lead us to recommend using the number of events in each study . We also discuss the calculation of measures of reclassification for multiple studies . We further show that comparison of differences in predictive ability across subgroups should be based only on within- study information and that combining measures of risk discrimination from case-control studies and prospect i ve studies is problematic . The concordance index and discrimination measure gave qualitatively similar results throughout . While the concordance index was very heterogeneous between studies , principally because of differing age ranges , the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous Objective . To evaluate the influence of inclusion criteria used in rheumatoid arthritis ( RA ) trials with adalimumab on clinical outcome and response . Methods . The different inclusion criteria of published trials of adalimumab in RA were separately applied to a large prospect i ve cohort of patients with RA treated with adalimumab ( AdRA cohort ) , thereby mimicking patient selection for a clinical trial . Clinical response and outcome in the result ing 11 projection groups were compared using the 28-joint Disease Activity Score ( DAS28 ) and time-averaged DAS28 as outcome measures of efficacy . Results . Thirteen trials ( n = 54–799 ) with 11 different sets of entry criteria were identified , result ing in 11 projection groups ( n = 22–168 ) . The DAS28 at baseline was similar in the original trial and each projection group based on this trial ( 5.1–6.4 , total AdRA cohort 5.1 ) . After 28 weeks , the efficacy varied substantially among the 11 projected groups ( change from baseline DAS28 : −1.65 to −2.65 , time-averaged DAS28 3.67–4.53 ) . Expressed as outcome ( DAS28 at 28 weeks ) , the efficacy was much more similar for almost all projection groups ( 3.5–4.0 ) and thus appeared to be mostly independent of disease activity at baseline . Conclusion . We observed that different inclusion criteria for clinical trials can have a marked effect on the expected response , i.e. , improvement from baseline . A novel finding is that final disease activity appeared much less dependent on initial disease activity . Our study suggests that for daily practice , one can assume that adalimumab treatment will on average result in a DAS28 between 3.5 and 4.0 after 28 weeks of treatment , regardless of baseline disease activity Objective CONCERTO was a r and omised , double-blind , parallel-armed study of methotrexate ( MTX ) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis ( RA ) . Methods Early , biologic and MTX-naive RA patients ( N=395 ) were evenly r and omised to open-label adalimumab ( 40 mg every other week ) plus weekly blinded 2.5 , 5 , 10 or 20 mg MTX for 26 weeks . Clinical , radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance . Results Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint , 28-joint count disease activity score with C reactive protein ( DAS28(CRP ) ) < 3.2 ( 42.9 % , 44.0 % , 56.6 % and 60.2 % for 2.5 , 5 , 10 or 20 mg/week MTX , respectively ) , DAS28(CRP ) < 2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab . No statistical differences in minimal clinical ly important differences in physical function were detected . Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by vali date d clinical indices ; differences comparing 10 and 20 mg MTX were minimal .  Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX . More patients experienced infectious adverse events with increasing MTX dose . Conclusions Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile . In early RA patients initiating adalimumab combination therapy , efficacy of 10 and 20 mg/week MTX appeared equivalent OBJECTIVE Joint damage is related to disease activity in rheumatoid arthritis ( RA ) , but the degree of its progression and the temporal associations between disease activity and joint damage are unclear . The aim of this study was to evaluate whether there is a latency in the effect of disease activity on radiographic progression in patients with RA . METHODS Data were obtained from the PREMIER trial , a 2-year r and omized , controlled clinical trial of adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in early RA .  Radiographic progression of joint damage was calculated using the modified total Sharp score in a subset of patients whose disease was in remission ( Simplified Disease Activity Index < or=3.3 ) in the second year of the trial . The progression of damage in the second year was compared between groups of patients whose disease was already in remission for an additional period of 3 , 6 , or 9 months during the first year . Analysis of variance was used to test for a linear trend . RESULTS Among 794 patients with early RA , 119 ( 15 % ) achieved sustained remission during the second year , with no difference in radiographic progression across the 3 treatment groups . Radiographic progression in the second year was significantly different between patients with 3 , 6 , or 9 additional months of remission during year 1 ( mean change in the modified Sharp score 1.19 in those with 3 additional months of remission versus 0.20 in those with 6 additional months of remission and -0.32 in those with 9 additional months of remission ; P<0.05 ) . The results were supported by similar findings in a series of sensitivity analyses . CONCLUSION These data indicate that the level of disease activity as well as the duration of remission affect subsequent progression of radiographic damage in RA . This latency between disease activity and its effects on radiographic progression should be considered when evaluating radiographic outcomes in trials of RA Rheumatoid arthritis ( RA ) is an autoimmune disease characterized by polyarticular joint inflammation result ing in massive tissue turnover . The turnover is partly mediated by an up-regulation of proteolytic enzymes , such as matrix metalloproteinases (MMPs).1 Matrix metalloproteinase 3 is 1 of the MMPs responsible for the degradation of the extracellular matrix (ECM).2 The MMP-mediated degradation of the main joint ECM proteins ( eg , types I and III collagen)3 results in the release of specific biomarkers such as the connective tissue biomarkers C1 M and C3M,4,5 known as protein fingerprints . These biomarkers are direct measures of changes to the tissue affected by the disease , in contrast to measurement of acute reactants such as C-reactive protein ( CRP ) or interleukin 6 ( IL-6 ) , which are upstream of tissue changes.6 Thus , protein fingerprint biomarkers may be more sensitive tools for measuring disease changes or changes caused by intervention . Protein fingerprint biomarkers have been associated with disease progression and response to therapy.7,8 CRPM is a protein fingerprint formed through degradation of CRP . In response to IL-6 , CRP is secreted by the liver as an acute phase reactant.9 C-reactive proteinaccumulates in inflamed tissue , where it is de grade d by MMPs , result ing in the release of CRPM.10 The ratio of C3 M to CRPM may depict MMP3 is 1 of the MMPs responsible for the degradation of the ECM ; its expression is highly elevated in the affected joint and may therefore be a relevant marker of proteolytic activity.2 Tocilizumab ( TCZ ) is approved in 2 doses for intravenous infusion:4 and 8 mg/kg . Although both doses provide structural progression and symptomatic relief , 8 mg/kg generally affords a higher level of response.11 Composite quantifiable measures depending on CRP were more reduced in 8 mg/kg compared with 4 mg/kg.12,13 As there are more adverse events in the higher dose,14 identification of those patients who respond most optimally to 4 mg/kg would significantly improve the benefit-to-risk assessment . The aim of present study was to identify responders to 4 mg/kg TCZ by measuring protein fingerprints at baseline Background : Early treatment prevents progression of joint damage in rheumatoid arthritis ( RA ) , but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria . Objective : To study the value of rheumatoid factor ( RF ) , anti-cyclic citrullinated peptide autoantibodies ( anti-CCP ) , and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis . Methods : The prospect i ve follow up inception cohort included 200 patients with very early ( <3 months ) inflammatory joint disease .  Autoantibodies  were measured at baseline and analysed in a tree based model which aim ed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone . Results : RA was diagnosed in 102 patients , while 98 developed other inflammatory arthropathies . Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml , above which anti-CCP and anti-RA33 had no additional diagnostic value . Remarkably , RF ⩾50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA , but overlapped considerably . Anti-RA33 was less specific and did not correlate with RF or anti-CCP . Among patients with RA , 72 % showed at least one of these three autoantibodies , compared with 15 % of non-RA patients . RF ⩾50 U/ml and anti-CCP were predictors of erosive disease , whereas anti-RA33 was associated with mild disease . Conclusions : Stepwise autoantibody testing in early inflammatory joint disease , starting with RF , followed by anti-CCP ( in patients with RF < 50 U/ml ) , and finally anti-RA33 , should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome OBJECTIVE To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences . METHODS Patients with active RA initiating their first treatment course of TNF-blocking therapy  were enrolled . The study period was March 1999 through September 2006 . The prospect i ve protocol included information on demographics , clinical characteristics of patients and response measures . Fulfilment of ACR 50 - 70 % improvement and European League Against Rheumatism ( EULAR ) good response or remission [ 28-joint disease activity score ( DAS28 ) < 2.6 ] at 3 months were chosen as primary outcome measures . Potential predictors of responses were identified using multivariate binary logistic regression models . RESULTS In total , 1565 patients were included in the study . Gender did not influence treatment response . Consistently , concomitant methotrexate ( MTX ) was significantly associated with EULAR remission , EULAR good response , ACR50 response and ACR70 response with odds ratios ( ORs ) 1.97 , 2.13 , 2.10 and 1.75 , respectively . Concurrent treatment with other DMARDs was also significantly associated with EULAR remission , EULAR good response and ACR50 response ( OR : 1.96 , 2.24 and 1.94 , respectively ) . Likewise , low HAQ at baseline consistently predicted good clinical outcome . Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 ( OR : 1.59 and 1.60 , respectively ) , whereas DAS28 score at baseline was inversely associated with EULAR remission ( OR : 0.78 ) . CONCLUSIONS In this observational study of patients with established RA , gender did not predict response to anti-TNF therapy , whereas treatment with concomitant DMARDs , especially MTX and low disability were associated with good response . Choice of outcome measures may influence the predictive value of baseline features OBJECTIVE To analyze the rate and baseline prognostic factors of clinical remission in a series of patients with early rheumatoid arthritis ( RA ) after 2 years of therapy based on a structured algorithm using disease-modifying anti-rheumatic drugs ( DMARDs )  in a clinical setting . To determine whether a good therapeutic response at 6 months of therapy is associated with remission at 2 years . METHODS One hundred and five patients ( 81 % female ) with early RA ( disease duration < 2 years ) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy , together with methylprednisolone ( 4 mg/day ) , were followed up for 2 years . The outcome variable was clinical remission after 2 years of DMARD therapy using the 28-joint disease activity score ( DAS28 < 2.6 ) . Clinical , biological , immunogenetic and radiographic data ( Larsen score ) were analyzed at study entry and after 6 , 12 , 18 and 24 months of follow-up . Therapeutic response was analyzed using the ACR and EULAR criteria . RESULTS Remission was observed in 34 patients ( 32.4 % ) after 2 years of follow-up . A baseline DAS28 score < 5.1 ( p = 0.004 ) , hemoglobin ( p = 0.04 ) and male gender ( p = 0.02 ) were associated with remission in the univariate analysis . In the multivariate logistic regression analysis , only a DAS28 < 5.1 was associated with remission at 2 years ( OR 4.1 , 95 % CI : 1.56;10.77 , p = 0.004 ) . The percentage of ACR50 responses after 6 months was significantly higher in patients with remission at 2 years than in those without ( 66.7 % vs 43.3 % ; p = 0.04 ) . Similar results were obtained when analyzing the good EULAR response ( 50 % vs 20.9 % ; p = 0.003 ) . Furthermore , when the therapeutic response at 6 months was included in the logistic regression model , only an ACR50 response ( OR 3.9 , 95 % CI 1.14;13.38 , p = 0.03 ) and a good EULAR response ( OR 6.23 , 95 % CI 1.61 ; 24.04 , p = 0.008 ) , but not an ACR20 response or a whole EULAR response were significantly associated with remission . CONCLUSION In a series of early RA patients treated using a structured algorithm with DMARDs and very low doses of glucocorticoids , clinical remission was observed in one-third of patients after 2 years . Low or moderate disease activity ( DAS28 < 5.1 ) at baseline and a good therapeutic response during the first months of therapy predicts clinical remission at 2 years Objective : To investigate whether rheumatoid factor isotypes and anti-cyclic citrullinated peptide ( anti-CCP ) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor α ( TNFα ) inhibitors .  Methods : The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease-modifying antirheumatic drugs . Patients were treated with infliximab ( n = 63 ) , etanercept ( n = 35 ) or adalimumab ( n = 34 ) . All patients completed 1 year of follow-up , and 126 were evaluable for clinical response according to the disease activity score ( DAS ) criteria . IgM , IgA and IgG rheumatoid factors and anti-CCP antibodies were assessed by ELISA both before anti-TNFα treatment and 1 year later . Results : The DAS response was reached in 66 % of evaluable patients ( 61 % infliximab , 65 % etanercept and 76 % adalimumab ; p = 0.354 ) . A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year . The frequency of positive tests for the different antibodies did not differ between responders and non-responders at baseline ; however , significantly higher IgA rheumatoid factor levels were reported by the non-responder group ( 130.4 U/ml ( interquartile range 13.8–276.7 ) v 24.8 U/ml ( 10.2–90.8 ) ; p = 0.003 ) . A significant decrease ( p<0.001 ) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment , whereas anti-CCP antibody levels were not significantly affected . Conclusions : According to the clinical response , anti-TNFα agents seem to reduce IgM , IgG and IgA rheumatoid factor levels . More interestingly , high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFα inhibitors The aim of this noninterventional study ( NIS ) was to analyze the changes in sickness absence , disease activity , and functional capacity in employed rheumatoid arthritis ( RA ) patients during adalimumab treatment . RA patients receiving adalimumab according to label instructions ( 40 mg every other week ) were evaluated at regular intervals in a multicenter prospect i ve NIS . Patients provided information on  sickness absence  in the 12 months preceding treatment initiation ( baseline ) and at months 6 and 12 . Disease activity was assessed by the Disease Activity Score using 28 joints , and physical function was assessed via the Hannover Functional Ability Question naire , a patient self- question naire comparable with the Health Assessment Question naire-Disability Index . We present data on 1,157 patients who were employed ( part time or full time ) at baseline . Patients were categorized by the length of sickness absence at baseline . At baseline , patients with absences of 6 weeks or more in the previous year ( n = 226 [ 19.5 % ] ) accounted for 77 % of the documented weeks of sickness absence , and patients with absences of more than 12 weeks ( n = 98 [ 8.5 % ] ) accounted for 54 % of sickness absence weeks . During 12 months of adalimumab treatment , disease activity decreased , functional capacity improved , and sickness absence was reduced . The greatest decrease in sickness absence was observed in patients with more than 12 weeks of sick leave in the year prior to adalimumab therapy . These patients also showed gains in function comparable with those observed in other employed patients . We conclude that sustaining and improving functional capacity represent the key to preservation of work capability Objectives To investigate the association of lifestyle factors with risk of inflammatory polyarthritis ( IP ) and rheumatoid arthritis ( RA ) . Methods The European Prospect i ve Investigation of Cancer , Norfolk , UK ( EPIC-Norfolk ) gathered lifestyle data from participants aged 40–79 years from 1993 to 1997 . Individuals who subsequently developed IP were identified by linkage with the Norfolk Arthritis Register . A Cox proportional hazard model was developed , and a score assigned to each risk factor to calculate the odds of developing IP . Results 25 455 EPIC participants were followed for a median ( IQR ) of 14.2 ( 12.9 , 15.3 ) years ; 184 developed incident IP  ( 138 cumulatively fulfilled criteria for RA ; 107 were seropositive ) . Pack-years of smoking were associated with increased risk of IP and RA in men ( HR 1.21 ( 95 % CI 1.08 to 1.37 ) per 10-pack-years ) and seropositive IP ( HR 1.24 ( 95 % CI 1.10 to 1.41 ) ) for all . Diabetes mellitus was associated with increased risk of IP ( HR 2.54 ( 95 % CI 1.26 to 5.09 ) ) , while alcohol ( HR 0.86 ( 95 % CI 0.74 to 0.99 ) per unit/day ) and higher social class ( HR 0.36 ( 95 % CI 0.15 to 0.89 ) for professionals vs manual workers ) were associated with reduced risk . Body mass index was associated with seronegative IP ( HR 2.75 ( 95 % CI 1.39 to 5.46 ) for obese vs normal-weight participants ) . In women , parity ( HR 2.81 ( 95 % CI 1.37 to 5.76 ) for ≥2 vs no children ) was associated with increased risk , and breast feeding ( HR 0.66 ( 95 % CI 0.46 to 0.94 ) for every 52 weeks of breast feeding ) was inversely associated with risk . Risk factors from the model were used to generate a ‘ risk score ’ . A total of 1159 ( 8.4 % ) women had scores reflecting a > 3-fold increased risk of IP over those with a score of 0 . Conclusions Several easily ascertained clinical and lifestyle factors can be used to stratify population s for risk of IP OBJECTIVE To describe the development and evaluation of a patient self-report case-finding method for rheumatoid arthritis ( RA ) not dependent on direct contact with the treating physicians . METHODS The American College of Rheumatology criteria for RA diagnosis were adapted for patient self-report using a question naire , and alternative scoring algorithms were evaluated to balance case-finding sensitivity and specificity . Positive rheumatoid factor tests were used to identify 1053 individuals in 2 large healthcare organizations ; 440 agreed to receive study material s. Case-finding results were vali date d by medical record review ( MRR ) for a r and om sample of 90 patients . Three scoring algorithms were compared with MRR for likelihood of RA diagnosis . Cases not classifiable by algorithm were flagged and review ed by 2 expert physicians for likelihood of RA diagnosis . RESULTS Pilot testing demonstrated that patients comprehended the question naire and were willing to answer the questions . Completed question naires were returned by 265 ( 60 % ) of the 440 patients contacted . Following expert physician review of 16 flagged cases in the 90-patient MRR sub sample , the most accurate scoring algorithm demonstrated 80 % sensitivity , 67 % specificity , 74 % accuracy , and 77 % positive predictive value for detecting early RA . CONCLUSION The case-finding method represents a promising tool for identifying RA patients , with potential application in research and quality -assurance activities . RELEVANCE This case-finding method should be useful in research and quality -assurance efforts requiring identification of RA patients treated by all types of providers in healthcare organizations in which central ized laboratory data are available The objective of this study was to identify predictors for remission or low disease activity ( LDA ) in established rheumatoid arthritis ( RA ) at 12 months of anti-TNF-α therapy . We have performed a prospect i ve observational study in 90 consecutive patients with active RA receiving TNF-α inhibitors .  Baseline and st and ard assessment s were done every 3 months , including individual parameters ( clinical and biological ) and composite activity scores ( 28-joint disease activity score , DAS28 ) . The primary outcome measure was DAS28-based EULAR response criteria . The multivariate logistic regression was used to analyze the association between disease activity and several RA baseline characteristics . Of the RA , 78.8 % was classified as good responders based on the EULAR-DAS28 criteria , 44.4 % RA achieving remission ( DAS28 ≤ 2.6 ) and 34.4 % , LDA ( DAS28 ≤ 3.2 ) . Parameters associated with an increased likelihood of remission and LDA were initial DAS28-erythrocyte sedimentation rate ≤7 ( odds ratio ( OR ) 3.3 , 95 % confidence interval ( CI ) 2.03–5.81 ; OR 1.8 , 95 % CI 1.09–6.68 ) , Health Assessment Question naire Disability Index ≤ 2 ( OR 7.0 , 95 % CI 1.56–31.91 ; OR 1.3 , 95 % CI 1.03–5.79 ) , C-reactive protein level ≤20 mg/l ( OR 1.5 , 95 % CI 0.29–8.22 ; OR 0.5 , 95 % CI0.08–2.97 ) , rheumatoid factor ≤20 IU/ml ( OR 18.9 , 95 % CI 10.79–38.36 ; OR 32.9 , 95 % CI 4.03–269 ) , anti-cyclic citrullinated peptide antibodies ≤40 IU/ml ( OR 3.5 , 95 % CI 0.67–18.19 ; OR 1.2 , 95 % CI 1.02–1.59 ) ,  concurrent  prednisolone ( OR 0.2 , 95 % CI 0.05–0.36 ; OR 0.2 , 95 % CI 0.06–0.63 ) , methotrexate or leflunomide ( OR 1.6 , 95 % CI 1.2–13.53 ; OR 2.9 , 95 % CI 1.20–4.36 ) . A predictive matrix for remission and LDA in established active RA patients receiving TNF-α inhibitors was proposed . Further studies are necessary to confirm the value of such matrix in particular RA setting s , leading to optimization of the use of anti-TNF-α therapy Objectives : To compare the occurrence of drug-free remission , functional ability and radiological damage after 4 years of response-driven treatment according to four different treatment strategies for rheumatoid arthritis ( RA ) . Methods : Patients with recent-onset , active RA ( n = 508 ) were r and omly assigned to four different treatment strategies : ( 1 ) sequential monotherapy ; ( 2 ) step-up combination therapy ; ( 3 ) initial combination therapy with prednisone and ( 4 ) initial combination therapy with infliximab . Treatment was adjusted based on 3-monthly disease activity score ( DAS ) assessment s , aim ing at a DAS ⩽2.4 . From the third year , patients with a sustained DAS < 1.6 discontinued treatment . Results : In total , 43 % of patients were in remission ( DAS < 1.6 ) at 4 years and 13 % were in drug-free remission : 14 % , 12 % , 8 % and 18 % of patients in groups 1–4 , respectively . The absence of anti-cyclic citrullinated peptide antibodies , male gender and short symptom duration were independently associated with drug-free remission . Functional ability and remission were maintained in all four groups with the continuation of DAS-driven treatment , without significant differences between the groups . Significant progression of joint damage was observed in 38 % and 31 % of patients in groups 3 and 4 versus 51 % and 54 % of patients in groups 1 and 2 ( p<0.05 , group 4 versus groups 1 and 2 , group 3 versus group 2 ) . Conclusions : In patients with recent-onset active RA  , drug-free remission was achieved in up to 18 % of patients . DAS-driven treatment maintained clinical and functional improvement , independent of the treatment strategy . Joint damage progression remained significantly lower after initial combination therapy compared with initial monotherapy Objective To analyse the role of multibiomarker  disease  activity ( MBDA ) score in predicting disease relapses in patients with rheumatoid arthritis ( RA ) in sustained remission who tapered disease modifying antirheumatic drug ( DMARD ) therapy in RETRO , a prospect i ve r and omised controlled trial . Methods MBDA scores ( scale 1–100 ) were determined based on 12 inflammation markers in baseline serum sample s from 94 patients of the RETRO study .  MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs . Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse . Results Moderate-to-high MBDA scores were found in 33 % of patients with RA overall . Twice as many patients who relapsed ( 58 % ) had moderate/high MBDA compared with patients who remained in remission ( 21 % ) . Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission ( N=94 ; p=0.0001 ) and those tapering/stopping ( N=59 ; p=0.0001 ) . Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody ( ACPA ) status . Relapse rates were low ( 13 % ) in patients who were MBDA−/ACPA− , moderate in patients who were MBDA+/ACPA− ( 33.3 % ) and MBDA−ACPA+ ( 31.8 % ) and high in patients who were MBDA+/ACPA+ ( 76.4 % ) . Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering . If combined with ACPA testing , MBDA allowed prediction of relapse in more than 80 % of the patients . Trial registration number EudraCT 2009 - 015740 - 42 OBJECTIVE To compare radiographic outcomes in patients with active early erosive rheumatoid arthritis ( RA ) who were treated with methotrexate ( MTX ) and gold sodium thiomalate ( GSTM ) . METHODS A total of 174 patients from two centres were r and omly assigned to receive weekly i.m . injections for 12 months of either 15 mg MTX or 50 mg GSTM in a double-blind fashion . Radiographic evaluations including st and ardized scoring of 38 joints of the h and s , wrists and forefeet , and count of eroded joints , were carried out at baseline and after 6 and 12 months in all patients , including withdrawals . RESULTS An intention-to-treat analysis revealed no statistically significant difference in the progression of radiographic scores between treatment groups after 6 months ( 3.4 with MTX vs 2.6 with GSTM , P = 0.66 ) and after 12 months ( 6.0 vs 4.8 , P = 0.44 ) . A similar pattern was observed for the number of joints with erosions . The slope of radiographic progression was significantly reduced in the second half-year compared to the first 6 months in both groups . Erythrocyte sedimentation rate and C-reactive protein at baseline , and the presence of rheumatoid factor ( RF ) , were the main predictors of progression in bivariate analysis . RF remained as the only predictor for radiographic outcome in multivariable analysis . CONCLUSION In parallel to clinical improvement , both GSTM and MTX reduce the slope of radiographic progression in patients with active erosive RA OBJECTIVE To describe the longitudinal radiographic course of rheumatoid arthritis ( RA ) , and to identify and quantitate predictors of radiographic progression . METHODS This prospect i ve , longitudinal study of radiographic progression and clinical predictors of RA involved 256 patients with RA who were seen within the first 2 years of disease ( mean 0.77 years ) and were followed up for up to 19 years . Participants underwent a total of 6,278 clinical assessment s  ( mean 24.5 ) and 934 paired radiographs ( mean 3.1 , range 2 - 6 ) . Clinical assessment s at every visit included determination of the erythrocyte sedimentation rate ( ESR ) , grip strength , pain scores , tender joint counts , and anxiety and depression measurements . Regression analyses utilized time-integrated predictors . RESULTS Overall , radiographic progression rates , as measured by the summary Sharp scores , appeared constant over the course of RA . The strongest correlate of progression was the time-integrated ESR ( rho=0.53 ) . This association grew stronger with time . At 0 - 5 years , 5 - 10 years , 10 - 15 years , and 15 - 20 years , correlations were 0.40 , 0.50 , 0.65 , and 0.74 , respectively , and for the period 10 - 20 years , the correlation was 0.67 . In multivariate models , the mean ESR , mean grip strength , rheumatoid factor positivity , and tender joint count were independent predictors of radiographic progression . CONCLUSION Radiographic damage occurs at a constant rate in RA , and is not greater early in RA or reduced later in the course of the illness . Acute-phase reactants are , by far , the strongest determinants of progression Objective : To investigate outcome as measured by health status , disease process , and damage in an unselected group of patients with early rheumatoid arthritis ( RA ) monitored prospect ively for 10 years and to search for prognostic factors . Patients and methods : 183 patients with RA with disease duration < 2 years were assessed annually at a team care unit . Health status was measured by the  Health Assessment Question naire ( HAQ ) and functional class .  Disease process was assessed by clinical and laboratory measures of disease activity and evaluation of disease course . Damage was quantified as occurrence of major extra-articular manifestations and need for large joint replacements . Possible predictive factors were evaluated by logistic regression analyses . Results : 168/183 patients completed the entire follow up period . Of all 183 patients , 137 ( 75 % ) had been treated with disease modifying antirheumatic drugs and 84 ( 46 % ) with low dose oral glucocorticoids . After 10 years 158 patients ( 94 % ) managed daily life activities independently ( functional class I – II ) . As measured by the HAQ 20 % had almost no disability , 28 % were mildly disabled , and 10 % were seriously disabled . Median HAQ score had increased from 0.8 to 1.1 ( p<0.001 ) . Disease activity was significantly reduced . 133 patients ( 79 % ) had a relapsing remitting disease course and 30 patients ( 18 % ) were in remission as defined by the American College of Rheumatology criteria . Thirty patients ( 17 % ) had undergone large joint replacements . Fifteen patients ( 8 % ) had developed major extra-articular complications . The HAQ score during the first three months predicted disability at 10 years with an odds ratio of 13.4 . Conclusions : Prospect i ve studies such as this give important knowledge of the variable long term prognosis of RA and provide necessary background information for clinical trials of new treatment modalities OBJECTIVE Adipose tissue has immunomodulating effects in rheumatoid arthritis ( RA ) , although the exact role is , at present , unclear . The purpose of this study was to determine whether body mass index ( BMI ) affects response to  infliximab  in RA patients investigated prospect ively . METHODS In 89 patients with active RA , the BMI was calculated before initiation of infliximab treatment  ( 3 mg/kg intravenously ) . After 16 weeks of treatment , changes in disease activity were assessed with the Disease Activity Score in 28 joints ( DAS28 ) . RESULTS The mean ± SD BMI was 26 ± 5 kg/m(2 ) ( range 17 - 42 ) . The BMI correlated positively with the DAS28 at baseline ( r = 0.34 , P = 0.001 ) . Since selection of study patients according to DAS28 values could influence the clinical response to tumor necrosis factor ( TNF ) blockade due to regression to the mean because the clinical response is itself based on the change in the DAS28 values , analysis of covariance was used to correct for the baseline DAS28 . A highly significant , negative association between the BMI and the absolute decrease in the DAS28 after 16 weeks ( P = 0.001 ) was found also when adjusted for anti-citrullinated protein antibodies . CONCLUSION Although the infliximab dosage is based on body weight , RA patients with a high BMI responded less well to infliximab , a finding that held true when adjusted for the baseline DAS28 or anti-citrullinated protein antibody status . These results support the notion that adipose tissue may be involved in the pathophysiology of RA and could have implication s for other immune-mediated inflammatory conditions treated with TNF antagonists This study evaluates prospect ively whether baseline scores [ Health Assessment Question naire ( HAQ ) and SF-36 ] can predict clinical and radiographic evolution in a cohort of early rheumatoid arthritis ( RA ) during a 3-year follow-up . Forty consecutive early RA patients were followed for 3 years , while receiving st and ardized treatment according to a pre-established protocol . HAQ and SF-36 were administered at the initial evaluation and at 3 , 6 , 12 , 18 , 24 and 36 months .  H and s and feet radiographs  were obtained at the initial evaluation and at 12 , 24 and 36 months . Preselected outcomes were the occurrence of radiographic erosions , the achievement of an EULAR remission , low disease activity status and the need for biological therapy .  The mean age at onset was 45 years with a 90 % female predominance . Erosions were found in 42 % of patients at T0 and in 70 % after 3 years ( P < 0.001 ) . At T0 , the proportion of patients in remission , low , moderate or high disease activity was 0 , 0 , 7.5 and 92.5 % and 22.5 , 7.5 , 32.5 and 37.5 % , respectively , at 3 years . The mean baseline HAQ score was 1.89 and 0.77 by the third year ( P < 0.0001 ) . Most SF-36 domains showed significant improvement except for general state and vitality .  Biological therapy was deemed necessary in 22.5 % of patients . The initial HAQ and SF-36 scores were not associated with clinical remission , bone erosions or the need for biological therapy at 36 months . The HAQ and SF-36 scores measured at baseline could not predict at 3 years , the preselected outcomes in a Brazilian cohort The objectives of this study was to assess , using clinical and magnetic resonance imaging ( MRI ) criteria , the efficacy of combination infliximab therapy in patients with active rheumatoid arthritis ( RA ) refractory to methotrexate ( MTX ) treatment and to ascertain whether the changes in MRI parameters correlate with the clinical response . Four infusions of infliximab ( 3 mg/kg ) at weeks 0 , 2 , 6 , and 14 were added to a stable background dose of MTX in 19 patients with active disease . Clinical parameters were assessed before each infusion and at week 14 . Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at baseline and week 14 . Synovitis severity , volume of synovitis , and synovial perfusion indices were evaluated . Significant improvement in all clinical disease activity parameters was seen at week 14 with reduction in C-reactive protein ( CRP ) , erythrocyte sedimentation rate ( ESR ) , and DAS28 . Sixty-eight percent of patients achieved ACR20 . MRI disease activity parameters also significantly decreased after treatment with reduction in grading of synovitis , volume of active synovitis , and perfusion enhancement slope . Significant positive correlations were seen between the baseline volume of synovitis and the pain score ( r=0.65 ) , patient global score ( r=0.68 ) , and health assessment question naire ( HAQ ) score ( r=0.46 ) . In conclusion , addition of infliximab to methotrexate rapidly reduces inflammation in longst and ing patients with RA . Assessment of enhancing synovial volume and perfusion indices on serial MRI examination was helpful in documenting the effect of treatment over this short period Clinical and laboratory measurements taken at the onset of rheumatoid arthritis in 149 patients were compared with the severity of radiological changes seen at 3 years in the h and s and feet , and cervical spine . The strongest association with the severity of peripheral radiological damage was rheumatoid factor ( p less than 0.0001 for both the latex titre and RAHA titre ) . Subluxation of the cervical spine was associated only with the presence of HLA-Dw2 ( p less than 0.02 ) and HLA-B7 cross-reacting group ( p less than 0.02 ) . Discriminant function analysis utilizing latex titre , RAHA titre , haemoglobin level , and platelet count predicted the development of erosive or nonerosive disease in 79 % . This method was less successful in predicting the actual severity of erosive damage and was not improved by the addition of HLA data . Radiological outcome in the cervical spine was successfully predicted in 82 % using HLA-Dw2 , HLA-B27 and age of onset of disease . It is concluded that the best predictors of erosive disease were st and ard laboratory features measured at onset , but that more powerful discriminant factors are needed if these are to influence clinical practice . Further prospect i ve studies will establish whether rheumatoid involvement of the cervical spine is an expression of the influence of HLA determinants in this disease OBJECTIVE To compare the efficacy and safety of subcutaneous ( SC ) versus oral administration of methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) . METHODS MTX-naive patients with active RA ( Disease Activity Score in 28 joints > or= 4 ) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to r and omization . Patients were r and omly assigned to receive 15 mg/week of MTX either orally ( 2 7.5-mg tablets plus a dummy prefilled syringe ; n=187 patients ) or SC ( prefilled syringe containing 10 mg/ml plus 2 dummy tablets ; n=188 patients ) for 24 weeks . At week 16 , patients who did not meet the American College of Rheumatology criteria for 20 % improvement ( ACR20 ) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks , still in a blinded manner . The primary outcome was an ACR20 response at 24 weeks . RESULTS At week 24 , significantly more patients treated with SC MTX than with oral MTX showed ACR20 ( 78 % versus 70 % ) and ACR70 ( 41 % versus 33 % ) responses .  Patients with a disease duration > or= 12 months had even higher ACR20 response rates ( 89 % for SC administration and 63 % for oral ) . In 52 of the ACR20 nonresponders ( 14 % ) , treatment was switched at week 16 . Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX result ed in 30 % and 23 % ACR20 response rates , respectively , in these patients . MTX was well tolerated . The rate of adverse events was similar in all groups . CONCLUSION This 6-month prospect i ve , r and omized , controlled trial is the first to examine oral versus SC administration of MTX . We found that SC administration was significantly more effective than oral administration of the same MTX dosage . There was no difference in tolerability Objective : Treating early active rheumatoid arthritis ( RA ) with disease modifying antirheumatic drug ( DMARD ) monotherapy achieves incomplete outcomes and intensive treatment seems preferable . As the relative benefits of combining two DMARDs , one DMARD with glucocorticoids and two DMARDs with glucocorticoids are uncertain we defined them in a factorial trial . Methods : A 2-year r and omised double-blind factorial trial in patients with RA within 2 years of diagnosis treated with methotrexate  studied the benefits of added ciclosporin , 9 months intensive prednisolone or both ( triple therapy ) . The primary outcome was the number of patients with new erosions . Secondary outcomes included Larsen ’s x-ray scores , disability , quality of life and adverse events . Findings : 1391 patients were screened and 467 r and omised . Over 2 years 132 ( 28 % ) changed therapy and 88 ( 19 % ) were lost to follow-up . The number of patients with new erosions was reduced by nearly half by adding ciclosporin or prednisolone ( p = 0.01 and 0.03 ) ; both treatments reduced increases in Larsen ’s x-ray scores by over 2 units ( p = 0.008 and 0.003 ) . A further reduction in erosive damage was seen with combined use of both treatments . Their effects on erosive damage appeared independent . Triple therapy reduced disability and improved quality of life compared with methotrexate ; ciclosporin and prednisolone acted synergistically . More patients withdrew because of adverse events with triple therapy , without an increase in serious adverse effects . Conclusions : This study confirms the existence of a “ window of opportunity ” in early RA , when intensive combination therapy produces sustained benefits on damage and disability . Although methotrexate – prednisolone combinations reduce erosive damage , the synergistic effect of two DMARDs is needed to improve quality of life OBJECTIVE To study the prognostic value of the antiperinuclear factor ( APF ) , determined by an indirect immunofluorescence test ( IIF ) and a recently developed anti-citrullinated cyclic peptide ( CCP ) ELISA , in combination with rheumatoid factor ( RF ) status , in early RA ( < 1 year ) . METHODS A total of 249 participants in a r and omized trial of treatment strategies were divided into 4 groups according to their APF ( or CCP ) and RF status at baseline . Differences in disability , joint involvement and radiological damage over a 3-year period were analysed . RESULTS APF-IIF results differed from CCP-ELISA in 42 cases ( 17 % ) ; 38 of the 42 had a positive IIF and negative ELISA value . Disability after 3 years did not differ significantly between the RF and APF groups . APF- patients had significantly lower Thompson joint scores compared to APF+ patients ( 6 vs 24 for CCP-ELISA ; 2 vs 24 for IIF ) . RF+APF+ patients exhibited more radiological damage compared to RF-APF- patients . RF+APF- and RF-APF+ patients had intermediate scores . Within the RF+ and RF- groups , APF+ was associated with more radiological damage and thus yielded prognostic information in addition to RF . In this respect , the results of ELISA and IIF were comparable . Thirty percent of the RF+APF+ patients had a radiological score higher than 45 , compared to 13 % of the RF+APF- , none of the RF-APF+ , and 2 % of RF-APF- patients ( p < 0.001 ) . In addition , more large joints were affected in APF+ than in APF- patients , while no difference was observed between RF+ and RF- patients . CONCLUSION APF has prognostic value in addition to RF for joint involvement and radiological damage in early RA . The CCP-ELISA technique for APF assessment may facilitate its use in clinical practice . However , the prognostic value of the two tests lies in their ability to predict mild disease . Reliable identification at baseline of individual patients with progressive disease is still not possible BACKGROUND Arthritis is the most common cause of disability among US adults . Few studies have comprehensively examined factors associated with disability in this population . OBJECTIVE To investigate the relationship between a number of disease and non-disease related factors and disability in sample of adults with self-reported doctor-diagnosed arthritis . METHODS Participants ( n = 396 ) taking part in a r and omized controlled trial of arthritis self-management completed a  comprehensive survey assessing a number of demographic , arthritis-specific , health-related , behavioral , and psychological variables at baseline . Disability , as measured by the Health Assessment Question naire ( HAQ )  , was also measured . Hierarchical regression models examined the independent associations between blocks of variables and disability . RESULTS Demographic variables ( R(2 ) = 0.13 ) , arthritis-specific demographics ( i.e. , type , medication use ; ΔR(2 ) = 0.16 ) , physical health-related variables ( ΔR(2 ) = 0.06 ) , arthritis-specific symptoms ( ΔR(2 ) = 0.12 ) , health behaviors ( ΔR(2 ) = 0.00 ) , and psychological variables ( ΔR(2 ) = 0.03 ) explained 50 % of the variance in disability score ( R(2 ) = 0.50 ) . With the exception of health behaviors , the addition of each block of variables significantly improved the model , explaining additional variance in HAQ scores ( p < 0.0001 ) . In the final model , older age , less than a high school education , rheumatoid arthritis , greater arthritis duration , taking steroids , taking narcotics , greater pain , greater stiffness , greater depressive symptoms , and lower arthritis self-efficacy were associated with greater disability whereas male gender , fibromyalgia , and excellent/very good health were associated with less disability . CONCLUSIONS A number of disease and non-disease related variables were associated with disability . These findings suggest that disability in adults with arthritis may be a complicated phenomenon ; such complexity may make decreasing disability in this population challenging Improved underst and ing of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research . Ample evidence suggests a role for Th17 cells in rheumatoid arthritis . We hypothesized that CD4+CD161 + cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis . Therefore , in a cross-sectional study , we investigated the occurrence of CD4+CD161 + T-cells in seropositive arthralgia patients who are at risk for developing rheumatoid arthritis and in newly diagnosed rheumatoid arthritis patients . In a prospect i ve study , we evaluated the effect of methotrexate treatment on circulating CD4+CD161 + T-cells . Next , we assessed if these cells can be detected at the level of the RA joints . Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients . In contrast , circulating CD4+CD161+T-cells were decreased in newly diagnosed rheumatoid arthritis patients . The decrease in CD4+CD161 + T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count . Methotrexate treatment led to normalization of CD4+CD161 + T-cells and reduced disease activity . CD4+CD161 + T cells were readily detected in synovial tissues from both early and late-stage rheumatoid arthritis . In addition , synovial fluid from late-stage disease was found to be enriched for CD4+CD161 + T-cells . Notably , synovial fluid accumulated CD4+CD161+T-cells showed skewing towards the Th1 phenotype as evidence d by increased interferon-γ expression . The changes in peripheral numbers of CD4+CD161 + T-cells in seropositive arthralgia and early rheumatoid arthritis and the enrichment of these cells at the level of the joint predict a role for CD4+CD161 + T-cells in the early immune events leading to clinical synovitis . Our findings may add to the development of RA prediction models and provide opportunities for early intervention Background : Smoking is a well-established environmental risk factor for the development of rheumatoid arthritis ( RA ) . However , it remains unclear whether smoking influences RA disease progression and whether smokers have more radiographic damage progression than non-smokers over time . Objective : To compare the rates of radiographic damage progression in current smokers and non-smokers in a large prospect i ve RA cohort . Methods : The SCQM-RA is a population -based registry monitoring disease activity , radiographic damage and symptoms at regular intervals . All patients in the SCQM-RA data base with sequential plain radiographs were included .  Joint erosions were assessed in 38 h and and foot joints with a vali date d scoring method . The rate of erosion progression was analysed using multivariate longitudinal regression models and adjusted for potential confounders . Results : 2004 RA patients with a mean of 3.6 sequential radiographs and 3.1 years of follow-up were included . The 545 ( 27 % ) current smokers smoked on average 16 cigarettes per day and had a mean past smoking exposure of 20.6 pack-years . Radiographic joint damage progressed at a similar rate in current smokers and non-smokers ( p = 0.26 ) . However , smoking intensity was associated with a significant inverse dose – response ; heavy smokers ( > 1 pack-day ) progressed significantly less than non-smokers or moderate smokers ( p<0.001 ) . Conclusion : Radiographic joint damage progressed at an equivalent rate in smokers and non-smokers . Furthermore , a significant trend was observed for reduced radiographic progression and generally more favourable functional scores among heavy smokers , suggesting that cigarette smoke does not accelerate RA disease progression Abstract Objective : To assess how use of a multi-biomarker disease activity ( MBDA ) blood test for rheumatoid arthritis ( RA ) affects treatment decisions made by health care providers ( HCPs ) in clinical practice . Research design and methods : At routine office visits , 101 patients with RA were assessed by their HCPs ( N = 6 ) , and they provided blood sample s for MBDA testing . HCPs completed surveys before and after viewing the MBDA test result , recording dosage and frequency for all planned RA medications and physician global assessment of disease activity . Frequency and types of change in treatment plan that result ed from viewing the MBDA test result were determined . Main outcome measure : Percentage of cases in which the HCP changed the planned treatment after viewing the MBDA test result . Results : Prior to HCP review of the MBDA test , disease modifying anti-rheumatic drug ( DMARD ) use by the 101 patients included methotrexate in 62 % of patients ; hydroxychloroquine 29 % ; TNF inhibitor 42 % ; non-TNF inhibitor biologic agent 19 % ; and other drugs at lower frequencies . Review of MBDA test results changed HCP treatment decisions in 38 cases ( 38 % ) , of which 18 involved starting , discontinuing or switching a biologic or non-biologic DMARD . Other changes involved drug dosage , frequency or route of administration . The total frequency of use of the major classes of drug therapy changed by < 5 % . Treatment plans changed 63 % of the time when the MBDA test result was perceived as being not consistent or somewhat consistent with the HCP assessment of disease activity . Study limitations : Limited sample size ; lack of control group ; no longitudinal follow-up . Conclusions : The addition of the MBDA test to clinical assessment led to meaningful changes in the treatment plans of 38 % of RA patients being cared for by HCPs in office practice . Even though treatment was potentially improved , the overall quantity of drug use was minimally affected Objectives To evaluate clinical remission with subcutaneous abatacept plus methotrexate ( MTX ) and abatacept monotherapy at 12 months in patients with early rheumatoid arthritis ( RA ) , and maintenance of remission following the rapid withdrawal of all RA treatment . Methods In the Assessing Very Early Rheumatoid arthritis Treatment phase 3b trial , patients with early active RA were r and omised to double-blind , weekly , subcutaneous abatacept 125 mg plus MTX , abatacept 125 mg monotherapy , or MTX for 12 months . Patients with low disease activity ( Disease Activity Score (DAS)28 ( C reactive protein ( CRP ) ) < 3.2 ) at month 12 entered a 12-month period of withdrawal of all RA therapy . The co primary endpoints were the proportion of patients with DAS28 ( CRP ) < 2.6 at month 12 and both months 12 and 18 , for abatacept plus MTX versus MTX . Results Patients had < 2 years of RA symptoms , DAS28 ( CRP ) ≥3.2 , anticitrullinated peptide-2 antibody positivity and 95.2 % were rheumatoid factor positive . For abatacept plus MTX versus MTX  , DAS28 ( CRP ) < 2.6 was achieved in 60.9 % versus 45.2 % ( p=0.010 ) at 12 months , and following treatment withdrawal , in 14.8 % versus 7.8 % ( p=0.045 ) at both 12 and 18 months . DAS28 ( CRP ) < 2.6 was achieved for abatacept monotherapy in 42.5 % ( month 12 ) and 12.4 % ( both months 12 and 18 ) . Both abatacept arms had a safety profile comparable with MTX alone . Conclusions Abatacept plus MTX demonstrated robust efficacy compared with MTX alone in early RA , with a good safety profile . The achievement of sustained remission following withdrawal of all RA therapy suggests an effect of abatacept 's mechanism on autoimmune processes . Trial registration number NCT01142726 Introduction UK guidelines recommend that all early active rheumatoid arthritis ( RA ) patients are offered combination disease-modifying antirheumatic drugs ( DMARDs ) and short-term corticosteroids . Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA may differ in their treatment responses . We used data from a r and omized controlled trial - the Combination Anti-Rheumatic Drugs in Early RA ( CARDERA ) trial - to examine whether responses to intensive combination treatments in early RA differ by ACPA status . Methods The CARDERA trial r and omized 467 early active RA patients to receive : ( 1 ) methotrexate , ( 2 ) methotrexate/ciclosporin , ( 3 ) methotrexate/prednisolone or ( 4 ) methotrexate/ciclosporin/prednisolone in a factorial- design . Patients were assessed every six months for two years . In this analysis we evaluated 431 patients with available ACPA status . To minimize multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline for each outcome ( Larsen , disease activity scores on a 28-joint count ( DAS28 ) , Health Assessment Question naire ( HAQ ) , EuroQol , SF-36 physical component summary ( PCS ) and mental component summary ( MCS ) scores ) . When a significant interaction was present , mean changes in outcomes were compared by treatment group at each time point using t-tests stratified by ACPA status . Odds ratios ( ORs ) for the onset of new erosions with treatment were calculated stratified by ACPA . Results ACPA status influenced the need for combination treatments to reduce radiological progression . ACPA-positive patients had significant reductions in Larsen score progression with all treatments . ACPA-positive patients receiving triple therapy had the greatest benefits : two-year mean Larsen score increases comprised 3.66 ( 95 % confidence interval ( CI ) 2.27 to 5.05 ) with triple therapy and 9.58 ( 95 % CI 6.76 to 12.39 ) with monotherapy ; OR for new erosions with triple therapy versus monotherapy was 0.32 ( 95 % CI 0.14 to 0.72 ; P = 0.003 ) . ACPA-negative patients had minimal radiological progression irrespective of treatment . Corticosteroid ’s impact on improving DAS28/PCS scores was confined to ACPA-positive RA . Conclusions ACPA status influences the need for combination DMARDs and high-dose tapering corticosteroids in early RA . In CARDERA , combination therapy was only required to prevent radiological progression in ACPA-positive patients ; corticosteroids only provided significant disease activity and physical health improvements in ACPA-positive disease . This suggests ACPA is an important biomarker for guiding treatment decisions in early RA.Trial registration Current Controlled Trials IS RCT Objectives To evaluate the separate effects of erosions ( E ) ( bone damage ) , joint space narrowing ( JSN ) ( cartilage loss ) and (sub)luxation ( SLUX ) ( soft tissue damage ) in four different joint groups on physical disability in rheumatoid arthritis ( RA ) . Methods 3-year follow-up data from the Rheumatoid Arthritis PreventIon of structural Damage ( RAPID ) 1 and 2 trials were used . These r and omised controlled trials compared certolizumab plus methotrexate ( MTX ) versus MTX in patients with RA .  Physical function was measured by Health Assessment Question naire ( HAQ ) . Radiographic damage was measured by the van der Heijde-modified Sharp score ; separate scores for E , JSN and SLUX were available . Generalised estimating equations were performed to assess the relationship between HAQ and E , JSN and SLUX scores , separately and in all joint groups . Results In separate models for each type of damage and after adjusting for age , gender , baseline disease activity and treatment group , E and JSN were more strongly associated with HAQ than with SLUX . In combined models , JSN was the only type of lesion associated with HAQ when all joints were included together . When separate joint groups were analysed , E in the wrist and JSN in the metacarpophalangeal joints ( MCPs ) were most strongly associated with function . Conclusions Among RA-related joint damage , cartilage loss quantified by JSN is an important determinant of physical function . However , when analysing joint groups separately , erosive damage in the wrist and JSN in the MCPs had the most important influence on disability . These data indicate that the comprehensive assessment of joint damage is needed to reliably reflect disease-related damage OBJECTIVE Treatment algorithms in RA include factors associated with poor prognosis ; however , many patients remain erosion free despite years of disease . Our objective was to characterize the group of RA patients without erosions and identify its clinical predictors . METHODS Our study was conducted within a prospect i ve observational cohort of RA patients recruited from the outpatient practice of an academic medical centre . We studied patients with bilateral h and radiographs at cohort baseline and 2-year follow-up  assessed with  Sharp/van der Heijde scores ( SHS ) . The primary outcome was erosion-free status at baseline and 2-year follow-up . We assessed baseline values of the following as potential correlates : age at RA onset , gender , RA duration , BMI , 28-joint DAS ( DAS-28 ) , CRP , anti-CCP status , tender and swollen joint counts , functional status [ multidimensional HAQ ( MDHAQ ) ] , tobacco use and RA treatments . Variables with P ≤ 0.25 in the univariate analyses were assessed using backward selection in multivariable logistic regression models . RESULTS Of the 271 subjects included , 21 % ( n = 56 ) were considered erosion free . Forty-six per cent ( n = 26 ) of this group was anti-CCP positive compared with 56 % ( n = 121 ) in subjects with erosions present . Mean RA duration for erosion-free subjects was 3.9 years compared with 4.6 years in erosive subjects . Treatments for RA did not differ between the two groups . In the multivariable-adjusted analysis , significant predictors of erosion-free status were younger age at onset and shorter RA duration . CONCLUSION In our cohort , 21 % of subjects were erosion free at baseline and 2 years . Few baseline clinical characteristics significantly predicted erosion-free status Objectives To identify predictive factors of radiological progression in early arthritis patients treated by remission-steered treatment .  Methods In the IMPROVED study , 610 patients with early rheumatoid arthritis ( RA ) or undifferentiated arthritis ( UA ) were treated with methotrexate ( MTX ) and a tapered high dose of prednisone . Patients in early remission ( disease activity score ( DAS ) < 1.6 after 4 months ) tapered prednisone to zero . Patients not in early remission were r and omised to arm 1 : MTX plus hydroxychloroquine , sulfasalazine and prednisone , or to arm 2 : MTX plus adalimumab .  Predictors of radiological progression ( ≥0.5 Sharp/van der Heijde score ; SHS ) after 2 years were assessed using logistic regression analysis . Results Median ( IQR ) SHS progression in 488 patients was 0 ( 0–0 ) point , without differences between RA or UA patients or between treatment arms . In only 50/488 patients , the SHS progression was ≥0.5 : 33 ( 66 % ) were in the early DAS remission group , 9 ( 18 % ) in arm 1 , 5 ( 10 % ) in arm 2 , 3 ( 6 % ) in the outside of protocol group . Age ( OR ( 95 % CI ) : 1.03 ( 1.00 to 1.06 ) ) and the combined presence of anticarbamylated protein antibodies ( anti-CarP ) and anticitrullinated protein antibodies ( ACPA ) ( 2.54 ( 1.16 to 5.58 ) ) were independent predictors for SHS progression . Symptom duration < 12 weeks showed a trend . Conclusions After 2 years of remission steered treatment in early arthritis patients , there was limited SHS progression in only a small group of patients . Numerically , patients who had achieved early DAS remission had more SHS progression than other patients . Positivity for both anti-CarP and ACPA and age were independently associated with SHS progression . Trial registration numbers IS RCT N Register number 11916566 and EudraCT number 2006 06186 - 16 Objectives Evaluate relationships between MRI and clinical /laboratory/radiographic findings in rheumatoid arthritis ( RA ) . Methods 637 methotrexate-naive patients ( GO-BEFORE ) and 444 patients with active RA despite methotrexate ( GO-FORWARD ) were r and omly assigned to subcutaneous placebo + methotrexate , golimumab 100 mg + placebo , golimumab 50 mg + methotrexate , or golimumab 100 mg + methotrexate every-4-weeks . In GO-BEFORE(n=318 ) and GO-FORWARD(n=240 ) sub studies , MRI of dominant wrist/metacarpophalangeal joints were scored for synovitis , bone oedema and bone erosion ( RA MRI scoring ( RAMRIS ) system ) . Relationships between RAMRIS scores and serum C-reactive protein ( CRP ) , 28-joint count disease activity score ( DAS28–CRP ) and van der Heijde modified Sharp ( vdH-S ) scores were assessed . Results Baseline and weeks 24/28 DAS28–CRP , CRP , and vdH-S generally correlated well with baseline and week 24 RAMRIS synovitis , oedema and erosion scores . Early ( week 4 ) CRP changes correlated with later ( week 12 ) RAMRIS synovitis/oedema change scores ; earlier ( week 12 ) changes in some RAMRIS scores correlated with later ( weeks 24/28 ) changes in vdH-S. Significant correlations between RAMRIS change scores and clinical /radiographic change scores were weak . Conclusions MRI and clinical /laboratory/radiographic measures generally correlated well . Associations between earlier changes in CRP and later changes in RAMRIS synovitis/osteitis were observed . Changes in MRI and clinical /radiographic measures did not correlate well , probably because MRI is more sensitive than radiographs and more objective than DAS28–CRP OBJECTIVE To evaluate the long-term effectiveness and safety of 10 years of adalimumab ( ADA ) treatment in DMARD-refractory RA patients and to analyse efficacy based on RF status and baseline disease duration . METHODS DE020 was a multicentre , phase 3 , open-label continuation study . Adult RA patients who received s.c . ADA ( 40 mg every other week or monthly ) in one of four early assessment studies could receive ADA for ≤10 years in DE020 . Assessment s included the 28-joint DAS with CRP ( DAS28-CRP ) , Simplified Disease Activity Index ( SDAI ) , HAQ Disability Index ( HAQ-DI ) and safety as events per 100 patient-years . RESULTS Of 846 enrolled patients , mean age at baseline was 55.6 years , 78.1 % were women , mean disease duration was 11.7 years and 27.0 % were RF(- ) . Among 286 ( 33.8 % ) patients who completed 10 years of ADA , 168/236 ( 71.2 % ) achieved DAS28-CRP ≤3.2 , 101/238 ( 42.4 % ) achieved HAQ-DI < 0.5 and 90/241 ( 37.3 % ) achieved DAS28-CRP ≤3.2 plus HAQ-DI < 0.5 . DAS28-CRP- or SDAI-based remission was observed in 135/236 ( 57.2 % ) and 70/236 ( 29.7 % ) patients , respectively . Effectiveness outcomes were similar regardless of RF status . Higher proportions of patients with shorter vs longer baseline disease duration ( ≤2 vs > 2 years ) achieved HAQ-DI < 0.5 ( 60.6 % vs 39.5 % ; P = 0.023 ) and DAS28-CRP ≤3.2 plus HAQ-DI < 0.5 ( 58.1 % vs 32.5 % ; P = 0.006 ) . Adverse events ( 317.2 events per 100 patient-years ) during ADA exposure were consistent with the expected safety profile for TNF inhibitors . CONCLUSION ADA led to sustained clinical and functional responses in the 33.8 % of treatment-refractory RA patients who completed 10 years of treatment . Patients with shorter disease duration achieved better outcomes , highlighting the need for early treatment . No unexpected safety findings were observed . TRIAL REGISTRATION Clinical Trials.gov , http://www . clinical trials.gov , NCT00195650 Objective . To create a tool to predict probability of remission and low disease activity ( LDA ) in patients with RA being considered for anti-TNF treatment in clinical practice . Methods . We analysed data from GO-MORE , an open-label , multinational , prospect i ve study in biologic-naïve patients with active RA ( DAS28-ESR ⩾3.2 ) despite DMARD therapy . Patients received 50 mg s.c . golimumab ( GLM ) once monthly for 6 months . In secondary analyses , regression models were used to determine the best set of baseline factors to predict remission ( DAS28-ESR < 2.6 ) at month 6 and LDA ( DAS28-ESR ⩽3.2 ) at month 1 . Results . In 3280 efficacy-evaluable patients , of 12 factors included in initial regression models predicting remission or LDA , six were retained in final multivariable models . Greater likelihood of LDA and remission was associated with being male ; younger age ; lower HAQ , ESR ( or CRP ) and tender joint count ( or swollen joint count ) scores ; and absence of comorbidities . In models predicting 1- , 3- and 6-month LDA or remission , area under the receiver operating curve was 0.648–0.809 ( R2 = 0.0397–0.1078 ) . The models also predicted 6-month HAQ and EuroQoL-5-dimension scores . A series of matrices were developed to easily show predicted rates of remission and LDA . Conclusion . A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA , based on a combination of six baseline characteristics . The tool could help provide practical guidance in selection of c and i date s for anti-TNF therapy Introduction The objectives of this study were to determine the predictive factors of long-term radiographic outcome of rheumatoid arthritis ( RA ) and to describe the relationship between joint damage and disability over the course of the disease . Methods A cohort of 191 patients with early RA referred from primary care physicians were prospect ively followed for 10 years . To determine the predictive factors of radiographic outcome , univariate analysis of the relationship between baseline values and outcome measures was undertaken using a chi-squared or Fisher 's exact test . Stepwise multiple logistic regression was also performed to select independent prognostic factors . Results From data available for 112 patients , univariate analysis revealed a total Sharp score at 10 years that was significantly correlated with erythrocyte sedimentation rate ( ESR ) , presence and level of IgA rheumatoid factor , presence of an anti-citrullinated protein antibody ( ACPA ) , serum level of matrix metalloproteinase-3 and radiographic score at baseline . Logistic regression identified the baseline erosion score to be the most important baseline parameter as an independent prognostic factor of total radiographic score at 10 years ( odds ratio = 5.64 ; 95 % confidence interval = 1.78 to 17.86 ) . After excluding radiographic scores from the entry parameters , the presence of ACPA and ESR were also predictive of the final total Sharp score . The Health Assessment Question naire ( HAQ ) score was strongly correlated with disease activity parameters , such as disease activity score and pain , at baseline and at three , five and 10 years . No correlation was found between total radiographic Sharp score and HAQ score throughout the study . Conclusions In this prospect i ve study , baseline radiographic score , ESR and ACPA were the best predictive factors of 10-year radiographic outcome in early RA . HAQ disability was associated with disease activity throughout the 10-year follow-up but not with joint damage . This discrepancy with previous reports may be due in part to the early start of therapy with disease-modifying anti-rheumatic drugs To evaluate the responsiveness of power Doppler ultrasonography ( PDUS ) in comparison with conventional measures of disease activity and structural damage in rheumatoid arthritis ( RA ) patients receiving tocilizumab ( TCZ ) . Seven RA patients with active arthritis were enrolled in the study and prospect ively monitored for 12 months . They were treated with TCZ ( 8 mg/kg ) every 4 weeks as monotherapy or in combination with disease-modifying antirheumatic drugs ( DMARDs ) . Clinical , laboratory , and ultrasound examinations were conducted at baseline , 1 , 3 , 6 , 9 , and 12 months . Power Doppler ( PD ) signals were grade d from 0 to 3 in 24 joints , and total PD score was calculated as the sum of scores of individual joints . One-year radiographic progression of the h and s was estimated by using Genant-modified Sharp scoring . The averages of the clinical parameters rapidly improved , and all patients achieved good response within 6 months based on st and ard 28-joint Disease Activity Score ( DAS28 ) . Although the average total PD score declined in parallel with clinical improvement , radiography of the h and s showed progression of destruction in the joints where PD signals remained , even among clinical responders . ΔSharp score correlated with the time-integrated value ( TIV ) of total PD scores ( Δtotal Sharp score : r = 0.77 , P = 0.04 ; Δerosion : r = 0.78 , P = 0.04 ; Δjoint-space narrowing ( JSN ) : r = 0.75 , P = 0.05 ) , but not with TIVs of clinical parameters including DAS28 . PDUS can independently evaluate disease activity in RA patients  receiving TCZ  and is superior to DAS28 , especially in predicting joint destruction OBJECTIVES Adalimumab , etanercept and infliximab are effective TNF inhibitors ( TNFis ) in the treatment of RA , but no r and omized clinical trials have compared the three agents . Prior observational data are not consistent . We compared their effectiveness over 1 year in a prospect i ve cohort . METHODS Analyses were performed on subjects ' first episode of TNFi use in the Rheumatic Diseases Portuguese Register , Reuma.pt . The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use . Comparisons were performed using conventional adjusted logistic regression , as well as matching subjects across the three agents using a propensity score . In addition , baseline predictors of treatment response to TNFi were identified . RESULTS The study cohort included 617 RA patients , 250 starting etanercept , 206 infliximab and 161 adalimumab .  Good response was achieved by 59.6 % for adalimumab , 59.2 % for etanercept and 51.9 % for infliximab ( P = 0.21 ) . The modelled probability of good response did not significantly differ across agents ( etanercept vs adalimumab OR = 0.97 , 95 % CI 0.55 , 1.71 ; etanercept vs infliximab OR = 1.25 , 95 % CI 0.74 , 2.12 ; infliximab vs adalimumab OR = 0.80 , 95 % CI 0.47 , 1.36 ) . Matched propensity score analyses also showed no significant treatment response differences . Greater educational attainment was a predictor of better response , while smoking , presence of ACPA , glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response . CONCLUSION Over 1 year , we found no difference in effectiveness between adalimumab , etanercept and infliximab Objective There is a need for comparative studies to provide evidence -based treatment guidance for biologic agents in rheumatoid arthritis ( RA ) . Therefore , this study was undertaken as the first head-to-head comparison of subcutaneous ( SC ) abatacept and SC adalimumab , both administered along with background methotrexate ( MTX ) , for the treatment of RA . Methods Patients with active RA who were naive to treatment with biologic agents and had an inadequate response to MTX were r and omly assigned to receive 125 mg SC abatacept weekly or 40 mg SC adalimumab biweekly , both given in combination with MTX , in a 2-year study . The primary end point was treatment noninferiority , assessed according to the American College of Rheumatology 20 % improvement response ( ACR20 ) at 1 year . Results Of the 646 patients who were r and omized and treated , 86.2 % receiving SC  abatacept and 82 % receiving SC adalimumab completed 12 months of treatment . At 1 year , 64.8 % of patients in the SC abatacept group and 63.4 % in the SC adalimumab group demonstrated an ACR20 response ; the estimated difference between groups was 1.8 % ( 95 % confidence interval −5.6 % , 9.2 % ) , thus demonstrating the noninferiority of abatacept compared to adalimumab . All efficacy measures showed similar results and kinetics of response between treatments . The rate of radiographic nonprogression ( defined as a total modified Sharp/van der Heijde score [ SHS ] less than or equal to the smallest detectable change ) was 84.8 % for SC abatacept – treated patients and 88.6 % for SC adalimumab – treated patients , while the mean change from baseline in the total SHS was 0.58 and 0.38 , respectively . In the SC abatacept and SC adalimumab groups , the incidence of serious adverse events ( SAEs ) was 10.1 % and 9.1 % , respectively , and the rate of serious infections was 2.2 % and 2.7 % , respectively . In patients treated with SC abatacept , the frequency of discontinuations due to AEs was 3.5 % and discontinuations due to SAEs was 1.3 % , while in patients treated with SC adalimumab , the frequencies were 6.1 % and 3 % , respectively . Injection site reactions occurred in 3.8 % of patients receiving SC abatacept compared to 9.1 % of patients receiving SC adalimumab ( P = 0.006 ) . Conclusion The results demonstrate that SC abatacept and SC adalimumab have comparable efficacy in patients with RA , as shown by similar kinetics of response and comparable inhibition of radiographic progression over 1 year of treatment . The safety was generally similar , other than the occurrence of significantly more local injection site reactions in patients treated with SC adalimumab The objective of this review is to report on the progress of the Brigham and Women 's Hospital Rheumatoid Arthritis Sequential Study ( BRASS ) Registry data collection and summarize previous research in underst and ing therapeutic response to DMARDs using clinical and genetic data . The BRASS Registry , established in 2003 , is a large , single-centre , prospect i ve and observational cohort of 1100 RA patients . Patients with either new-onset or established RA disease are recruited from the practice s of rheumatologists . Annual visits collect information on demographics , 28-joint DAS-CRP3 ( DAS-28-CRP3 ) , medication use , comorbidities and functional status ( Modified Health Assessment Question naire , Short Form Health Survey 12 ) . Two published studies have utilized BRASS to examine genetic predictors of treatment response . In a cross-sectional study , examining the association between c and i date single nucleotide polymorphisms ( SNPs ) and disease activity in a subset of 120 RA patients on MTX monotherapy  , the minor allele of ATIC rs4673993 was associated with low disease activity ( P=0.01 , DAS-28-CRP3≤3.2 ) . In an international collaboration , 55 BRASS patients receiving anti-TNF therapy  were genotyped for 31 SNPs associated with the risk of RA . With our collaborators , we discovered an SNP at the protein tyrosine phosphatase , receptor type , C ( PTPRC ) gene locus that was associated with EULAR ' good response ' . With accurate data collection and the capacity to run genome-wide association studies and SNP analyses , the BRASS Registry has the ability to determine the contribution of genetic variants to disease onset and to assess their usefulness as biomarkers for treatment response and drug toxicity The aim of the Patient/Physician Reported Efficacy Determination In Clinical Practice Trial ( PREDICT ; Clinical Trials identifier NCT01255761 ) was to compare the  patient‐reported Routine Assessment of Patient Index Data 3 ( RAPID‐3 ) instrument with the investigator‐based Clinical Disease Activity Index ( CDAI ) for assessing certolizumab pegol ( CZP ) treatment response in rheumatoid arthritis patients at 12 weeks and to predict the treatment response at week 52 using the data from week 12 ( co primary end points ) Objective To investigate if a glucocorticoid ( GC ) response at 2 weeks , defined by EULAR response criteria , can predict active disease ( Disease Activity Score (DAS)>2.4 ) at 3 months . Methods For this study , data of the Treatment in the Rotterdam Early Arthritis Cohort study ( tREACH ) , an ongoing clinical trial that evaluates different induction therapies in early rheumatoid arthritis , were used . We selected patients who had a high probability of progressing to persistent arthritis ( > 70 % based on the prediction model of Visser ) . All patients within the high-probability stratum , who had a baseline DAS>2.2 and a DAS assessment at 2 weeks after r and omisation , were included ( n=120 ) . Besides GC response at 2 weeks , we investigated which other factors were associated with active disease ( DAS>2.4 ) after 3 months of disease-modifying antirheumatic drug ( DMARD ) treatment . All variables with a p≤0.25 were assessed in our logistic regression model with backward selection . Variables were eliminated until all remaining variables had a significant association ( p<0.05 ) . Results Patients who did not respond to GC bridging therapy at 2 weeks had an overall OR of having active disease at 3 months of 10.29 ( 95 % CI 3.34 to 31.64 ; p<0.001 ) in comparison with responders . The corrected OR was 14.00 ( 95 % CI 3.31 to 59.21 ; p<0.001 ) . Our final model predicting response at 3 months included the following variables : gender , GC response , induction therapy arms and baseline DAS , which had an explained variance of 39 % . Conclusions GC response at 2 weeks is a useful tool for recognising those patients who will probably have active disease ( DAS>2.4 ) after 3 months of DMARD treatment AIM To evaluate the efficacy and safety of four different treatment strategies for patients with early rheumatoid arthritis ( RA ) . METHODS In the BeSt study , 508 patients with newly diagnosed ( < 2 years ) active RA were r and omised to be treated according to four treatment strategies : 1 . sequential monotherapy , 2 . step up to combination therapy ( both starting with methotrexate ) , 3 . initial combination therapy with methotrexate , sulphasalazine , and a tapered high dose of prednisone , and 4 . initial combination therapy with methotrexate and infliximab . Three-monthly therapy adjustments were dictated by calculation of the Disease Activity Score ( DAS ) , with the goal to achieve and maintain a DAS < or= 2.4 . Functional ability was measured every 3 months with the Health Assessment Question naire . Radiographs of h and s and feet were assessed yearly , blinded for patient identity and treatment , and in r and om order , to measure joint damage progression ( Sharp/van der Heijde score ) . RESULTS After 2 years of treatment , 80 % of all patients achieved the goal of DAS < or= 2.4 , and 42 % reached clinical remission ( DAS < 1.6 ) . Initial combination therapy , either with prednisone ( group 3 ) or with infliximab ( group 4 ) , result ed in earlier improvement in functional ability , more continuous clinical remission ( DAS < 1.6 ) , and less joint damage progression than initial monotherapy ( groups 1 and 2 ) . Patients in groups 1 and 2 needed more therapy adjustments , including introduction of combination therapy with prednisone or infliximab , to achieve a DAS < or= 2.4 , whereas many patients in groups 3 and 4 were able to taper their medication to sulphasalazine or methotrexate , respectively , monotherapy . The adverse events profile was comparable in all groups . The presence or absence of rheumatoid factor , HLA DR4 , or anti-CCP was not associated with radiologic damage progression . CONCLUSION In patients with early , active RA , remarkable clinical improvement and suppression of joint damage progression can be achieved with frequent , objective ly steered treatment adjustments . The best chance for an early clinical and radiologic response lies with initial combination therapy with either methotrexate , sulphasalazine and prednisone or with methotrexate and infliximab , which can be tapered to DMARD monotherapy once low disease activity is achieved OBJECTIVE Previous studies have suggested a link between inflammation and central sensitization of pain in patients with RA . We conducted a prospect i ve cohort study to determine whether US Doppler ( USD ) ,  temporal summation ( TS ) of pain-assessed at baseline- and the potential interaction between them could predict the treatment response in RA . METHODS Patients were recruited from Departments of Rheumatology in the Copenhagen area and from private clinics . RA patients , who were scheduled to initiate therapy with either a conventional synthetic DMARD ( csDMARD ; including DMARD-naïve patients ) or a biologic DMARD ( bDMARD ) agent ( including bDMARD switch ) , were included and examined before the start of treatment and after 4 months . During the 4 months , patients received routine care from their treating rheumatologist . RESULTS Multiple regression analysis was conducted , with change in DAS28 as the dependent variable . In unadjusted models , baseline USD score was significantly associated with DAS28 ( β = 0.06 ; 95 % CI : 0.02 , 0.09 ; P < 0.001 ) , whereas TS and their interaction were not . After adjusting for age , sex , disease duration , baseline DAS28 and whether patients initiated a csDMARD or a bDMARD , the USD score was still significantly associated with change in DAS28 ( β = 0.032 ; 95 % CI : 0.001 , 0.064 ; P = 0.046 ) , whereas TS remained insignificant . CONCLUSION USD assessed at baseline is valuable as a prognostic factor for change in disease activity in ' real-life ' RA patients . We did not find evidence to suggest that TS or the interaction between USD and TS was prognostically important for this group of patients OBJECTIVE To compare the benefits of initiating treatment with methotrexate ( MTX ) and infliximab ( anti-tumor necrosis factor alpha [ anti-TNFalpha ] monoclonal antibody ) with those of MTX treatment alone in patients with rheumatoid arthritis ( RA ) of < or =3 years ' duration . METHODS RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor . One thous and forty-nine patients were r and omly assigned in a 4:5:5 ratio to 3 treatment groups : MTX-placebo , MTX-3 mg/kg infliximab , and MTX-6 mg/kg infliximab . MTX dosages were rapidly escalated to 20 mg/week , and infliximab or placebo infusions were given at weeks 0 , 2 , and 6 , and every 8 weeks thereafter through week 46 . RESULTS At week 54 , the median percentage of American College of Rheumatology improvement ( ACR-N ) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group ( 38.9 % and 46.7 % versus 26.4 % , respectively ; P < 0.001 for both comparisons ) . Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone ( mean + /- SD changes in van der Heijde modification of the total Sharp score at week 54 : 0.4 + /- 5.8 and 0.5 + /- 5.6 versus 3.7 + /- 9.6 , respectively ; P < 0.001 for each comparison ) . In addition , physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group . Infliximab therapy was associated with a significantly higher incidence of serious infections , especially pneumonia . CONCLUSION For patients with active RA in its early stages , combination therapy with MTX and infliximab provides greater clinical , radiographic , and functional benefits than treatment with MTX alone Aim Classifying more patients as rheumatoid arthritis ( RA ) ( 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA ) may improve treatment outcomes but may cause overtreatment in daily practice . The authors determined the efficacy of initial methotrexate ( MTX ) plus prednisone treatment in patients with 1987 or 2010 classified RA and undifferentiated arthritis ( UA ) . Method 610 recent onset RA or UA patients started with MTX 25 mg/week and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks .  Percentage remissions after 4 months were compared between RA ( 1987 or 2010 criteria ) and UA . Predictors for remission were identified . Results With the 2010 criteria , 19 % more patients were classified as RA than with the 1987 criteria , but similar remission rates were achieved : 291/479 ( 61 % ) 2010 classified RA and 211/264 ( 58 % ) 1987 classified RA patients ( p=0.52 ) , and 79/122 ( 65 % ) UA patients ( p=0.46 ) . Anticitrullinated protein antibodies ( ACPA ) positive RA patients achieved more remission ( 66 % ) than ACPA negative RA patients ( 51 % , p=0.001 ) , but also had a lower mean baseline Disease Activity Score ( DAS ) ( 3.2 vs 3.6 , p<0.001 ) . Independent predictors for remission were male sex , low joint counts , DAS and Health Assessment Question naire , low body mass index and ACPA positivity . Conclusion Initial treatment with MTX and a tapered high dose of prednisone results in similarly high remission percentages after 4 months ( about 60 % ) in RA patients , regardless of fulfilling the 1987 or 2010 criteria , and in UA patients . Independent predictors indicate that initiating treatment while disease activity is relatively low results in more remission OBJECTIVE To evaluate the ability of low-dose cyclosporin A ( CsA ) to control radiologic disease progression , and to assess the clinical efficacy and tolerability of CsA , compared with conventional disease-modifying antirheumatic drugs ( DMARDs ) , in patients with early active rheumatoid arthritis ( RA ) . METHODS In this long-term , multicenter , prospect i ve , open , blinded end point , r and omized trial , 361 consenting patients with early ( < 4 years since diagnosis ) active RA were enrolled . Of the eligible patients , 167 were treated with CsA at 3 mg/kg/day  , and 173 with DMARDs . The decision to use conventional antirheumatic drugs as controls was based on the fact that joint erosion could be expected to occur after 1 year regardless of the type of DMARD being used . The possibility of switching therapies in both groups was intended to keep the largest possible number of patients in the study . RESULTS Blinded evaluation of h and and foot radiographs after 12 months of treatment showed that CsA led to a significant ( P < 0.001 ) delay in the mean + /- SD progression in the eroded joint count ( 1.3 + /- 3.1 versus 2.4 + /- 3.0 for the control group ) and in the joint damage score ( 3.6 + /- 8.9 versus 6.9 + /- 9.1 for the control group ) , both measured by the Larsen-Dale method . When only the patients without erosion at baseline were considered ( 37 in the CsA-treated group and 54 in the control group ) , erosion appeared in only 10.8 % of the CsA-treated patients , but in 51.8 % of the controls ( P = 0.00005 ) . Low-dose CsA was as effective as traditional DMARDs in controlling clinical symptoms . Maintenance on the initially prescribed treatment regimen ( " survival on treatment " ) was also better at 12 months with CsA than with DMARDs ( 89.2 % versus 77.5 % ; P = 0.002 ) . The tolerability of CsA  was acceptable . CONCLUSION These 12-month results suggest that low-dose CsA decreases the rate of further joint damage in previously involved joints as well as the rate of new joint involvement in previously uninvolved joints , in patients with early RA Summary A total of 218 patients with early onset rheumatoid arthritis were entered into a prospect i ve study over fifteen years . Of these , 151 remained in the study at three years ( of whom 14 died ) , and a further 39 ( 23 deaths ) defaulted after this time . The severity of disease was assessed by four different methods . Although persistently active joint disease was recorded in 26 % of patients , only 13 % had severe functional impairment , and only 14 % developed severe erosions . An episode of RA lasting two to three years followed by complete remission with none or minimal sequelae ( “ non recurrent ” RA ) was present in 34 % . Using discriminant analysis , which selected rheumatoid factor , haemoglobin level and platelet count from a number of clinical and laboratory variables measured at onset , it was possible to predict three mutually exclusive outcome categories correctly in 50–60 % of patients depending on the method of assessment of outcome OBJECTIVE There are conflicting data concerning the role of HLA-DRB1 alleles in disease outcome in early rheumatoid arthritis . The exact role of these alleles in short-term outcome is determined in this large , prospect i ve , population -based study . METHODS We recruited 532 patients with inflammatory polyarthritis from the Norfolk Arthritis Register and typed  their sera for HLA-DRB1 alleles using polymerase chain reaction-based methods . Disease outcome was assessed at 2 years in terms of persistent joint inflammation , functional disability , and radiologic erosions . Results are expressed as risk ratios ( RR ) with 95 % confidence intervals ( 95 % CI ) . RESULTS There was no influence of HLA-DRB1 alleles , in any combination , on the likelihood of disease persistence , and only a modest effect on functional disability ( Health Assessment Question naire score > or = 1 ) . The most obvious effect was on the development of erosions ( RR 1.9 , 95 % CI 1.4 - 2.6 for those who carried at least 1 DRB1 shared epitope [ SE ] allele ) , with slightly greater effects for those who were homozygous for SE-bearing alleles ( RR 2.5 , 95 % CI 1.8 - 3.6 ) . This effect of HLA-DRB1 was restricted to patients whose sera were negative for rheumatoid factor . Among patients with erosions , HLA-DRB1 had no influence on the severity of radiologic damage ( defined as the number of eroded joints , or total Larsen score ) . CONCLUSION These data do not support routine HLA-DRB1 screening of patients with early arthritis to identify those at risk for subsequent severe disease OBJECTIVE To evaluate the effect of adalimumab treatment on clinical remission and /or minimal disease activity ( MDA ) in 6,610 patients with active rheumatoid arthritis ( RA ) who were enrolled in the Research in Active RA trial , a multinational , open-label , 12-week study with an optional extension period . METHODS Clinical remission was defined as a Disease Activity Score in 28 joints (DAS28)<2.6  , Simplified Disease Activity Index ( SDAI ) score < or=3.3 , or Clinical Disease Activity Index ( CDAI ) score < or=2.8 . MDA required absence of tender and swollen joints plus erythrocyte sedimentation rate (ESR)<or=10 mm/hour ; DAS28 score < or=2.85 ; or achievement of 5 of 7 core criteria for pain , swollen/tender joints , physical function , physician/patient global assessment , and ESR . Time to and time in remission/MDA and response predictors were analyzed using Kaplan-Meier estimates and Cox proportional hazards regression analysis , respectively . RESULTS A total of 38 % , 24 % , and 27 % of patients achieved remission defined as DAS28<2.6 , SDAI < or=3.3 , and CDAI < or=2.8 , respectively . MDA was observed in 45 % of patients by DAS28<or=2.85 , in 43 % by the core set of criteria , and in 13 % by absence of tender/swollen joints plus ESR < or=10 mm/hour . Median times in continuous remission and MDA were 3.4 and 4.4 months , respectively . Predictors for remission ( DAS28<2.6 ) and MDA ( DAS28<or=2.85 ) were male sex ; younger age ; concomitant disease-modifying antirheumatic drug use ; lower baseline DAS28 , CRP concentration , and Health Assessment Question naire disease index score ; < or=1 comorbidity ; and tumor necrosis factor antagonist naivety . CONCLUSION During adalimumab treatment , 25 % of patients experienced clinical remission and nearly half achieved MDA . To our knowledge , this analysis represents the largest prospect i ve clinical trial data set to be assessed using Outcome Measures in Rheumatology Clinical Trials MDA criteria OBJECTIVE To investigate the extent to which early radiologic damage is predicted by joint inflammation in patients with newly diagnosed rheumatoid arthritis ( RA ) . METHODS Regression analysis was performed on 1-year progression of total radiologic damage for baseline characteristics and cumulative disease activity measures , and the effects of continued joint inflammation on the progression of damage in separate joint groups were investigated . RESULTS Odds ratios for progression of total damage were 12 for the presence of rheumatoid factor , 5 for the presence of damage at baseline , and 2 for cumulative joint inflammation . A positive association between continued joint inflammation and progression of damage was found to be statistically significant for most joint groups . CONCLUSION Progression of radiologic damage in patients with newly diagnosed RA is independently associated with the presence of rheumatoid factor and damage at baseline and with cumulative joint inflammation OBJECTIVE To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis ( RA ) . METHODS A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospect ively followed up for 3 years .  Radiologic scores  ( as determined by Sharp 's method , modified by van der Heijde ) and radiologic progression  were used as outcome measures . Numerous baseline clinical , laboratory , genetic , and radiographic data were obtained . RESULTS The change in the total radiologic score for the patients followed up over 3 years was a mean + /- SD increase of 6.1 + /- 6.2 .  Radiologic progression  was observed in 71 of the 172 patients for whom there were data at the end of the study . By univariate analysis with Fisher 's exact test , radiologic scores  and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate ( ESR ) , C-reactive protein level , IgM and IgA rheumatoid factor positivity , antiperinuclear antibody positivity , radiologic scores , duration of morning stiffness , and RA-associated HLA-DRB1 * 04 genes . No correlation was demonstrated with sex , age , Disease Activity Score , swollen or tender joint counts , extraarticular manifestations , Health Assessment Question naire score , Ritchie Articular Index , patient 's assessment of pain , positivity for anti-heat-shock protein 90-kd antibodies , anticalpastatin antibodies , anti-RA33 antibodies , antinuclear antibodies , YKL-40 , or antikeratin antibodies , and HLA-DRB1 * 01 genes . The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity , DRB1 * 04 genes , pain score , and total radiologic score . Progression of joint damage was predicted by the ESR , IgM rheumatoid factor positivity , DRB1 * 04 genes , and erosions score at baseline . CONCLUSION Prognostic factors for radiographic damage in early RA were identified . A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients Sixty-four survivors from a prospect i ve study of early rheumatoid disease were assessed again at a mean of 15.2 years from presentation and their status compared with 29 patients who had died . Eleven of the dead and only two of the survivors had been treated with steroids . There was a small increase in mortality due to the disease itself but only one death was directly caused by it . As might be expected , those who died were older . In the first year of disease , they had lower haemoglobin levels , a lower body mass , higher sedimentation rates and higher levels of blood urea . One-fifth at entry to the study and two-fifths by the time of death , had poor functional capacity . Of 64 survivors , six had poor  functional capacity  at entry and nine after 15 years . Discriminant analysis was performed to identify the most powerful combination of early features predicting a poor functional outcome . A combination including early erosive change , seropositivity , poor grip strength and cervical subluxation predicted the outcome correctly in 73 % of survivors . Almost 60 % of survivors remained with or improved to normal function at 15 years suggesting that morbidity is not as bad as has been suggested in the past Background : Obesity is a state of chronic low- grade inflammation that predisposes people to several diseases and that is increasingly prevalent . Rheumatoid arthritis ( RA ) is marked by the presence of proinflammatory cytokines and , in general , the presence of high levels of inflammatory markers is associated with a severe disease course and joint damage . Objectives : To evaluate prospect ively ( a ) whether obesity is a risk factor for the development of RA and ( b ) whether the  body mass index ( BMI ) is associated with the amount of joint destruction in early RA after 3 years ’ follow-up . Methods : In a cohort of 570 patients with undifferentiated arthritis , the relation between the BMI  and the development of RA during 1 year of follow-up was assessed . In a cohort of 488 patients with early RA the correlation between the BMI and degree of radiological joint destruction ( Sharp – van der Heijde score ) after 3 years of follow-up was determined . The findings were replicated in an independent cohort of 247 patients with early RA . Results : Obesity did not influence the likelihood of developing RA . In both RA cohorts , the BMI was inversely correlated with the Sharp – van der Heijde score after 3 years ’ follow-up ( r = −0.15 , p = 0.025 for the Leiden EAC and r = −0.27 , p<0.001 for the replication cohort ) . Linear regression analyses in both cohorts showed that the BMI was independently and inversely associated with the level of joint destruction in anti-CCP-positive patients with RA , but not in anti-CCP-negative patients . Conclusions : A high BMI is associated with a less severe disease outcome in anti-CCP-positive patients with RA In medical research , continuous variables are often converted into categorical variables by grouping values into two or more categories . We consider in detail issues pertaining to creating just two groups , a common approach in clinical research . We argue that the simplicity achieved is gained at a cost ; dichotomization may create rather than avoid problems , notably a considerable loss of power and residual confounding . In addition , the use of a data -derived ' optimal ' cutpoint leads to serious bias . We illustrate the impact of dichotomization of continuous predictor variables using as a detailed case study a r and omized trial in primary biliary cirrhosis . Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models OBJECTIVES To investigate the prognostic significance of clinical and genetic markers on the outcome of patients with recent-onset rheumatoid arthritis ( RA ) treated actively with slow acting antirheumatic drugs ( SAARDs ) .  METHODS A total of 142 consecutive patients with early RA ( median disease duration of 7 months ) were treated according to the “ sawtooth ” strategy and prospect ively followed up for an average of 6.2 years . Several clinical parameters at start as well as genetic markers were related to the functional outcome ( ARA Functional class and HAQ disability score ) and radiographic joint damage ( Larsen ’s score ) at the latest visit . RESULTS In logistic regression analysis only Mallya score ( including morning stiffness , pain scale , grip strength , Ritchie ’s articular index , haemoglobin , and erythrocyte sedimentation rate ) at baseline , and Mallya score and rheumatoid factor ( RF ) positivity at one year were found to be of significance with respect to the radiographic outcome of the patients . Furthermore , at the latest visit HAQ score was related to radiographic score . At baseline the mean ages of the DR4 positive patients and the patients with RA associated DR alleles were statistically significantly lower than those without the above mentioned risk factors ( 44 v 49 , p=0.03 and 41 v 53 , p=0.04 , respectively ) . However , these genetic markers had no prognostic significance on the functional or radiographic outcome of the patients . CONCLUSION High clinical disease activity at baseline and RF positivity especially at one year after the institution of SAARD treatment are the best predictors of poor prognosis in early RA . However , from the clinical point of view , the disease outcome of an individual patient with early RA , can not be predicted accurately enough by present means OBJECTIVES To assess the occurrence of and predictive factors for  orthopaedic surgery  in an inception cohort of rheumatoid arthritis ( RA ) patients recruited and followed prospect ively for 5 yr in nine regions in Engl and . METHODS St and ard clinical , laboratory and radiological assessment s and all interventions were recorded at baseline and yearly in RA patients ( less than 2 yrs symptoms ) prior to the use of disease-modifying drugs .  RESULTS One thous and and sixty-four patients completed 5 yr of follow-up . Two hundred and sixty-four orthopaedic procedures for RA were performed in 181 ( 17 % ) patients at a median of 36.5 months from baseline . Seventy-five ( 7 % ) had replacements of major joints . Risk factors at baseline for large joint replacement surgery were a low haemoglobin concentration [ odds ratio scores ( OR ) 3.4 , 95 % confidence interval ( CI ) 2.1 - 5.8 ] and high scores for erythrocyte sedimentation rate ( ESR ) ( OR 3.2 , CI 1.8 - 5.3 ) , disease activity ( DAS ) ( OR 2.1 , CI 1.2 - 3.5 ) and Larsen X-rays ( OR 2.6 , CI 1.4 - 4.8 ) . For h and or foot joint surgery ( 4 % ) , risk factors included female gender ( OR 3.2 , CI 1.3 - 7.6 ) , joint score ( OR 2.3 , CI 1.2 - 4.3 ) , erosions ( OR 2.3 , CI 1.1 - 4.8 ) , DAS ( OR 2.4 , 1.3 - 4.5 ) and Health Assessment Question naire score ( OR 1.9 , CI 1.0 - 3.6 ) . No significant associations were seen for tendon , soft tissue or other minor procedures ( 6 % ) . The HLA-DRB1 RA shared epitope was associated with any type of orthopaedic surgery ( OR 1.7 , CI 1.1 - 2.7 ) . CONCLUSIONS Eleven per cent of RA patients treated with conventional drug therapy for 5 yr underwent large- or small-joint surgery , an outcome which could be compared against that for new disease-modifying drugs . Risk factors varied according to type of surgery , but included st and ard clinical and laboratory measures . In order to reduce the eventual need for surgery , a therapeutic target in the first year of RA is the suppression of disease activity , as measured by haemoglobin and ESR . These are useful details for clinicians , health professionals and patients Objective . Optimizing therapeutic strategies to induce remission requires an underst and ing of the initial features predicting remission . Currently no suitable model exists . We aim to develop a remission score using predictors of remission in early rheumatoid arthritis ( RA ) . Methods . We used a data set from a UK r and omized controlled trial that evaluated intensive treatment with conventional combination therapy , to develop a predictive model for 24-month remission . We studied 378 patients in the trial who received 24 months ’ treatment .  Our model was vali date d using data from a UK observational cohort ( Early RA Network , ERAN ) . A group of 194 patients was followed for 24 months .  Remission was defined as 28-joint Disease Activity Score < 2.6 . Logistic regression models were used to estimate the associations between remission and potential baseline predictors . Results . Multivariate logistic regression analyses showed age , sex , and tender joint count ( TJC ) were independently associated with 24-month remission . The multivariate remission score developed using the trial data correctly classified 80 % of patients . These findings were replicated using ERAN . The remission score has high specificity ( 98 % ) but low sensitivity ( 13 % ) . Combining data from the trial and ERAN , we also developed a simplified remission score that showed that younger men with a TJC of 5 or lower were most likely to achieve 24-month remission . Remission was least likely in older women with high TJC . Rheumatoid factor , rheumatoid nodules , and radiographic damage did not predict remission . Conclusion . Remission can be predicted using a score based on age , sex , and TJC . The score is relevant in clinical trial and routine practice setting Objective : To study factors associated with toxicity , final dose , and efficacy of methotrexate ( MTX ) in patients with rheumatoid arthritis ( RA ) . Methods : Data were used from a r and omised clinical 48 week trial on 411 patients with RA all treated with MTX  , comparing folates and placebo . Logistic regression was used to study the relation between baseline variables and various dependent factors , including hepatotoxicity ( alanine aminotransferase ⩾3 × upper limit of normal ) ,  MTX withdrawal , final MTX  dose ⩾15 mg/week , and  MTX efficacy . Results : Addition of folates to MTX treatment was strongly related to the lack of hepatotoxicity . Next to this , high body mass index was related to the occurrence of hepatotoxicity . Prior gastrointestinal ( GI ) events and younger age were related to the adverse event , diarrhoea . Hepatotoxicity and GI adverse events were the main reason for MTX withdrawal , which in turn was associated with the absence of folate supplementation , body mass index , prior GI events , and female sex . Renal function ( creatinine clearance ⩾50 ml/min ) was not associated with toxicity . Reaching a final dose of MTX of ⩾15 mg/week was related to folate supplementation and the absence of prior GI events . Efficacy of MTX treatment was associated with low disease activity at baseline , male sex , use of non-steroidal anti-inflammatory drugs ( NSAIDs ) , and lower creatinine clearance . Conclusions : MTX toxicity , final dose , and efficacy are influenced by folate supplementation . Baseline characteristics predicting the outcome of MTX treatment are mainly prior GI events , body mass index , sex , use of NSAIDs , and creatinine clearance To investigate a possible relationship between the presence of antineutrophil cytoplasmic antibodies ( ANCA ) , rheumatoid factor ( RF ) , antinuclear antibodies ( ANA ) , complement , disease activity and disease severity , 111 clinical ly well-documented RA patients were studied prospect ively for ANCA , RF , ANA , C-reactive protein ( CRP ) , total haemolytic complement ( CH50 ) and complement split product C3d . Disease activity and severity were also assessed clinical ly , as well as anamnestically , using the Hannover Activity of Daily Living Question naire , the functional Steinbrocker grade s , and numeric and verbal rating scales . At a serum dilution of 1:50 , 20 % of the 111 sera showed predominantly an atypical perinuclear staining pattern . There was no correlation between ANCA positivity and serological markers , disease activity and discase severity . Regarding previous therapies with disease-modifying antirheumatic drugs , ANCA+ patients took  sulphasalazine  significantly more often than ANCA- patients Abstract Objective : To assess effectiveness and safety of certolizumab PEGol ( CZP ) in rheumatoid arthritis ( RA ) patients after 12 months of treatment and to detect predictors of response . Methods : Observational longitudinal prospect i ve study of RA patients from 35 sites in Spain . Variables ( baseline , 3- and 12-month assessment ): sociodemographics , previous Disease Modifying Anti-Rheumatic Drug ( DMARD ) and previous Biological Therapies ( BT ) use ; TJC , SJC , ESR , CRP , DAS28 , SDAI . Response variables : TJC , SJC , CRP , ESR , and steroids dose reductions , EULAR Moderate/Good Response , SDAI response and remission , DAS28 remission . Safety variables : discontinuation due to side-effects . Descriptive , comparative and Logistic regression analyses were performed . Results : We included 168 patients : 79.2 % women , mean age 54.5 years ( ±13.2 SD ) , mean disease duration 7.5 years ( ±7.3 SD ) .  Mean number of prior DMARD : 1.4 ( ±1.2 SD ) , mean number of prior BT was 0.8 ( ±1.1 ) . Mean time on CZP  was 9.8 months ( ±3.4 SD ) . A total of 71.4 % were receiving CZP at 12-month assessment . Baseline predictors of response : lower prior number DMARD ; low number prior BT ; higher CRP , ESR , TJC , SJC , DAS28 and SDAI ( p < 0.05 ) scores . A 25/46.4 % Moderate/Good Response , a 20 % SDAI remission , and a 44 % DAS28 remission were observed . We observed 48 discontinuations ( 28.6 % ) , 31 due to partial or complete ineffectiveness , and 17 due to side-effects . Conclusions : CZP showed benefit in severe RA patients , with significant reduction of all effectiveness parameters , despite the high prevalence of previous BT exposure in our series . We found CRP , ESR , prior DMARD/BT number , TJC , SJC , DAS28 , and SDAI as baseline predictors of response . CZP was mostly well tolerated OBJECTIVE To determine the association of HLA-DRB1 , rheumatoid factor ( RF ) , and anti-citrullinated protein antibody ( ACPA ) status with progression of joint damage in early rheumatoid arthritis ( RA ) treated according to different treatment strategies . METHODS The present study was conducted using data from the BeSt study ( Beh and elstrategieën voor Reumatoide Artritis [ treatment strategies for rheumatoid arthritis ] ) , a r and omized trial comparing 4 targeted ( toward achievement of a Disease Activity Score [ DAS ] of < or = 2.4 ) treatment strategies : sequential monotherapy ( group 1 ) , step-up combination therapy ( group 2 ) , initial combination therapy with methotrexate , sulfasalazine , and prednisone ( group 3 ) , and initial combination therapy with methotrexate and infliximab ( group 4 ) , in 508 patients with early RA .  Multivariate logistic regression analysis was used to predict progressive disease ( increase of Sharp/van der Heijde score over 2 years beyond the smallest detectable change [ 4.6 ] ) according to the presence or absence of the shared epitope ( SE ) , DERAA , RF , and ACPA , with correction for other baseline characteristics . RESULTS Progressive disease could not be predicted by presence of the SE : the odds ratio in groups 1 , 2 , 3 , and 4 , respectively , was 1.4 , 2.6 , 1.9 , and 3.0 . DERAA carriership did not protect against progressive disease ( odds ratio 0.4 , 1.4 , 0.9 , and 0.9 in groups 1 , 2 , 3 , and 4 , respectively ) . RF positivity and ACPA positivity predicted progressive disease in group 1 ( odds ratio 4.7 [ 95 % confidence interval 1.5 - 14.5 ] for RF and 12.6 [ 95 % confidence interval 3.0 - 51.9 ] for ACPA ) , but not in groups 2 - 4 ( for RF , odds ratio [ 95 % confidence interval ] 1.5 [ 0.5 - 4.9 ] , 1.0 [ 0.3 - 3.3 ] , and 1.4 [ 0.4 - 4.8 ] in group 2 , group 3 , and group 4 , respectively ; for ACPA , odds ratio [ 95 % confidence interval ] 3.4 [ 0.8 - 14.2 ] , 1.7 [ 0.5 - 5.4 ] , and 1.8 [ 0.5 - 6.8 ] in group 2 , group 3 , and group 4 ) . CONCLUSION In patients with early RA treated with the goal of tight control of the DAS , no significant association between HLA-DRB1 status and radiographic progression was found . RF and ACPA were predictive of progressive disease only in patients treated with sequential monotherapy . These observations suggest that effective treatment can prevent radiographic progression , even in patients with risk factors for severe damage OBJECTIVE To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis ( RA ) after 1 yr of treatment with disease-modifying anti-rheumatic drugs ( DMARDs ) .  METHODS Sixty patients ( 47 females , 13 males ) with RA with a disease duration shorter than 2 yr [ mean ( s.d . ) duration 9.5+/-6.6 months ] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option , and were followed up for 1 yr .  Radiographic progression in the h and s and feet ( total radiographic Larsen score and the erosion joint count ) was used as the outcome variable . Clinical , laboratory , immunogenetic and radiographic data were obtained at study entry . Disease activity and response to therapy were measured at 6 and 12 months . RESULTS Erosive disease was found in 21.7 % of patients at baseline and in 38.3 % after 1 yr . Although a substantial reduction in disease activity was observed during the 1 yr follow-up [ disease activity score ( DAS28 ) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months , P < 0.001 ] , the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr . In 26.6 % of patients , a raised erosion joint count was observed after 1 yr . Radiographic progression in the total joint radiographic damage ( increase in Larsen score of > or=2 ) was observed in 36.6 % . In the multivariate analysis , baseline pain [ visual analogue scale ( VAS ) ] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count . Disease duration before study entry , VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage ( Larsen score ) . Baseline radiographic damage had the highest positive predictive value for progression . CONCLUSIONS Radiographic progression was observed in up to 36.6 % of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity . Baseline factors , such as VAS pain , disease duration until DMARD therapy , damage score at baseline and the presence of two copies of the shared epitope , were associated with radiographic progression OBJECTIVE The transforming growth factor beta superfamily member macrophage inhibitory cytokine 1 ( MIC-1 ) is expressed upon macrophage activation , regulated by the p53 pathway , and linked to clinical events in atherosclerosis and cancer . Since rheumatoid arthritis ( RA ) shares similar etiopathologic mechanisms with the above diseases , we sought to determine the clinical utility of determining MIC-1 serum levels and MIC-1 genotype in the management of RA . METHODS Ninety-one RA patients were recruited .  Serum was collected from 83 of these patients and  synovial biopsy sample s were collected from the remaining 8 patients . Of the 83 patients from whom serum was collected , 61 were treated on an outpatient basis ( defined as having nonsevere disease ) , and 22 patients went on to undergo hemopoietic stem cell transplantation ( HSCT ) ( defined as having severe disease ) . RESULTS Serum levels of MIC-1 were higher in RA patients and reflected disease severity independently of classic disease markers . MIC-1 was detected in rheumatoid synovial specimens , and allelic variation of MIC-1 was associated with earlier erosive disease and severe treatment-resistant chronic RA . Additionally , algorithms including serum and /or allelic variation in MIC-1 predicted response to HSCT , the presence of severe disease , and joint erosions . CONCLUSION Determination of serum levels of MIC-1 and MIC-1 genotype may be clinical ly useful in the management of RA as well as in selection of patients for HSCT , since they predict disease course and response to therapy . The data indicate a potential role for MIC-1 in RA pathogenesis . These results warrant larger prospect i ve studies to fully delineate and confirm a role for MIC-1 genotyping and serum estimation in patient selection for HSCT and in the management of RA OBJECTIVE To determine prognostic factors of disability in early rheumatoid arthritis ( RA ) and to investigate the radiological and functional course of the disease . METHODS A total of 191 patients with early RA ( diagnosed for less than one year ) according to American College of Rheumatology criteria were followed prospect ively for 5 years . At baseline and at endpoint ,  Stanford Health Assessment Question naire ( HAQ ) scores and radiological scores  ( Sharp 's score modified by van der Heijde ) were performed . Correlations between numerous baseline data and HAQ score at endpoint were analyzed , using nonparametric tests . A multilinear regression model was performed to select independent prognostic factors of HAQ disability . RESULTS During the 5-year followup , mean HAQ decreased from 1.3 ( + /- 0.7 ) to 0.6 ( + /- 0.6 ) . There were 98 ( 65.3 % ) patients with a score > 1 point at baseline , but only 46 ( 27.4 % ) after 3 years and 34 ( 21.8 % ) after 5 years . Moreover , 90 % of the patients had an improvement of the disability score . Final HAQ disability was associated with baseline values of HAQ score , Pain , Ritchie index , tender joint count , Disease Activity Score , erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , and erosion . Multivariate analysis selected baseline HAQ score , Ritchie index , ESR , CRP , and presence of erosion as independent prognostic factors of HAQ disability . The probability cutoff in the logistic model was selected to minimize the sum of false positive and false negative values : negative predictive value = 92.71 % , positive predictive value = 46.15 % , p = 0.408 . Sex , age , IgM and IgA rheumatoid factors , other tested autoantibodies , and HLA class II genes did not contribute significantly to prediction of the disability after 5 years . At baseline , mean scores were 3.6 units ( + /- 7.7 ) for total radiological score , 1.7 ( + /- 4.5 ) for erosion score , and 1.9 ( + /- 3.7 ) for joint space narrowing score . After 5 years , they were 17.9 + /- 22.3 , 6.9 + /- 9.5 , and 11.0 + /- 15.4 , respectively . No erosion was present at the start in 58.0 % of patients , compared to 24.2 % and 22.4 % at 3 and 5 years . Global radiographic progression concerned 87 patients ( 55.8 % ) during the 5 years . CONCLUSION During the first 5 years of RA , radiological damage increased progressively in half of the patients , whereas HAQ disability improved in most of them during the same period of time and could be predicted by baseline values of HAQ score , Ritchie index , ESR , CRP , and presence ( or absence ) of erosion Abstract Objective : To produce a practical algorithm to predict which patients with early rheumatoid arthritis will develop radiological erosions . Design : Primary care based prospect i ve cohort study . Setting : All general practice s in the Norwich Health Authority , Norfolk Subjects : 175 patients notified to the Norfolk Arthritis Register were visited by a metrologist soon after they had presented to their general practitioners with inflammatory polyarthritis , and again after a further 12 months . All the patients satisfied the American Rheumatism Association 's 1987 criteria for rheumatoid arthritis and were seen by a metrologist within six months of the onset of symptoms . The study population was r and omly split into a prediction sample ( n = 105 ) for generating the algorithm and a validation sample ( n = 70 ) for testing it . Main outcome measures : Predictor variables measured at baseline included rheumatoid factor status , swelling of specific joint areas , duration of morning stiffness , nodules , disability score , age , sex , and disease duration when the patient first presented . The outcome variable was the presence of radiological erosions in the h and s or feet , or both , after 12 months . Results : A simple algorithm based on a combination of three variables — a positive rheumatoid factor test , swelling of at least two large joints , and a disease duration of more than three months — was best able to predict erosions . When the accuracy of this algorithm was tested with the validation sample , the erosion status of 79 % of patients was predicted correctly . Conclusions : A simple algorithm based on three easily measured items of information can predict which patients are at high risk and which are at low risk of developing radiological erosions The purpose of this study was to assess the treatment benefit of golimumab + methotrexate ( MTX ) vs. MTX monotherapy in  MTX-naïve patients with severe active rheumatoid arthritis ( RA ) . This was a post hoc analysis of  MTX-naïve RA patients in the GO-BEFORE trial who were r and omized to receive placebo + MTX ( n = 160 ) , golimumab 50 mg + MTX  ( n = 159 ) , or golimumab 100 mg + MTX  ( n = 159 ) . Subsets of patients with severe disease were identified using these baseline criteria : C-reactive protein ( CRP ) ≥1.5 mg/dL , CRP ≥3.0 mg/dL , swollen joint count ( SJC ) ≥10 and tender joint count ( TJC ) ≥12 , SJC ≥ 20/TJC ≥ 12 , 28-joint  count Disease Activity Score using CRP ( DAS28-CRP ) > 5.1 , and anti-cyclic citrullinated peptide antibody-positive status . The treatment effect of golimumab + MTX vs. MTX alone was evaluated for these outcomes : the proportions of patients achieving ≥20 , 50 , and 70 % improvement in the American College of Rheumatology criteria ; DAS28-CRP European League Against Rheumatism response ; DAS28-CRP < 2.6 , clinical ly meaningful improvement in physical function ; and change in van der Heijde-Sharp score ≤0 at week 52 . Clinical response was greater in the golimumab + MTX groups vs. placebo + MTX for all of the outcomes evaluated . Furthermore , the treatment effect of golimumab + MTX was consistently greater among patients in the severe disease subsets when compared with the overall GO-BEFORE trial population . The treatment benefit of golimumab + MTX vs. MTX monotherapy was most pronounced within the subsets of patients with CRP ≥3.0 mg/dL and SJC ≥ 20/TJC ≥ 12 . Following treatment with golimumab + MTX  , improvements in RA signs/symptoms and in progression of structural damage were evident for the overall GO-BEFORE population , with the treatment effect more pronounced among patients with severe active disease OBJECTIVE To compare etanercept-induced improvement in disability of patients with recent onset of rheumatoid arthritis ( RA ) to that of patients with established RA . METHODS Health Assessment Question naire ( HAQ ) scores were collected over 3 years in 2 groups of patients with RA who were treated with etanercept .  The first group consisted of 207 patients with recent onset RA ( mean duration of 1 year ) who had not previously received methotrexate , and the second group consisted of 464 patients with established RA ( mean duration of 12 years ) who had failed one or more disease-modifying antirheumatic drugs .  RESULTS Baseline demographics and disease characteristics were similar in the 2 groups , except for HAQ scores and C-reactive protein levels , which were higher in the established RA group . Patients in both groups showed rapid and sustained clinical responses with etanercept therapy , but patients with recent onset RA showed significantly greater improvement in HAQ scores compared with patients with established RA . The difference in magnitude of HAQ score improvement between groups was observed as early as week 2 after initiation of etanercept and persisted throughout the 3-year time frame . At year 3 , significantly more patients with recent onset RA had a HAQ score of zero ( 26 % ) versus those with established RA ( 14 % , p = 0.0095 ) . CONCLUSION Although etanercept therapy significantly improved disability scores in both groups , patients with recent onset of RA showed greater benefit in HAQ scores than patients with established RA . These results support prompt treatment of RA at an early stage of disease to minimize patient disability Objective To investigate the 2-year clinical and radiological outcomes of patients with early rheumatoid arthritis ( RA ; symptom duration < 1 year ) who had initially responded well to methotrexate monotherapy .  Methods In the SWEFOT trial , all 487 patients started methotrexate ( target dose 20 mg/week ) . After 3–4 months , 147 had low disease activity , 28-joint based disease activity score ( DAS28 ) ≤3.2 . These patients were not r and omly selected but were followed in regular care for 2 years . Clinical outcomes and radiographic progression according to the van der Heijde modified Sharp ( SvdH ) score were analysed . Results The majority of the 147 patients continued on methotrexate monotherapy . After 1 and 2 years , DAS28 remission was achieved in 59.6 % and 71.8 % and mean observed DAS28 values were 2.53 and 2.25 , respectively . Despite the favourable clinical course , a proportion of the patients progressed radiographically with a mean ( SD ) increase in the SvdH score after 2 years of 3.90 ( 6.84 ) . There was no significant difference in progression between patients in DAS28 remission versus not in remission ( p=0.73 ) . At baseline , approximately half the patients had no radiographic damage , while after 2 years the proportion was approximately 20 % . Conclusion Most early RA patients who achieve low disease activity after 3–4 months of methotrexate monotherapy continue to have low disease activity during 2 years follow-up , and additional treatment is needed infrequently . Some radiological progression occurs in most patients , and may be marked or severe in some , even despite sustained DAS28 remission . Close monitoring for radiological progression is thus warranted OBJECTIVE To determine what baseline factors might be associated with response to an initial mild treatment regimen in patients with early rheumatoid arthritis ( RA ) . METHODS Open label 2-yr study of 111 consecutive patients with early RA of duration less than 1 yr . None of the patients had previously received disease-modifying anti-rheumatic drugs ( DMARDs ) . All patients were assigned to receive hydroxychloroquine ( HCQ ) at enrollment , and could also take non-steroidal anti-inflammatory drugs ( NSAIDs ) and prednisone . At any point during follow-up , patients not fulfilling the American College of Rheumatology ( ACR ) 50 criteria for improvement and /or who were taking prednisone > 10 mg/day were considered treatment failures and therapy changed to methotrexate ( MTX ) , 7.5 - 20 mg/week . Clinical , laboratory and immunogenetic factors potentially predictive of treatment assignment at month 24 were evaluated . RESULTS After 24 months of follow-up , a majority of patients ( 56/94 ) were either still on solo DMARD therapy with HCQ ( n = 49 ) or off DMARD therapy with controlled/quiescent disease ( n = 4 ) , and 38 patients were taking MTX ( including 11 in combination with other DMARDs ) . At month 24 , all but 9 patients met ACR50 criteria for treatment response . Features present at enrollment which were predictors of MTX therapy at month 24 were high pain score , baseline rheumatoid factor titre > 1:40 , higher number of swollen joints , and poor patient global assessment . The presence of HLA-C7xx at enrollment was also predictive of need for MTX  therapy . CONCLUSIONS This study suggests that even milder treatment with HCQ is greatly beneficial in patients with early RA . There continue to be very few consistently reliable predictors of treatment needs in patients with this disease Objective . Rapidly predicting future outcomes based on short-term clinical response would be helpful to optimize rheumatoid arthritis ( RA ) management in early disease . Our aim was to derive and vali date a clinical prediction rule to predict low disease activity ( LDA ) at 1 year among patients participating in the Treatment of Early Aggressive Rheumatoid Arthritis ( TEAR ) trial escalating RA therapy by adding either etanercept or sulfasalazine + hydroxychloroquine [ triple therapy ( TT ) ] after 6 months of methotrexate ( MTX ) therapy . Methods . Eligible subjects included in the derivation cohort ( used for model building , n = 186 ) were participants with moderate or higher disease activity [ Disease Activity Score 28-erythrocyte sedimentation rate ( DAS-ESR ) > 3.2 ] despite 24 weeks of MTX monotherapy who added either etanercept or sulfasalazine + hydroxychloroquine . Clinical characteristics measured within the next 12 weeks were used to predict LDA 1 year later using multivariable logistic regression . Validation was performed in the cohort of TEAR patients r and omized to initially receive either MTX + etanercept or  TT . Results . The derivation cohort yielded 3 prediction models of varying complexity that included age , DAS28 at various timepoints , body mass index , and ESR ( area under the receiver-operator characteristic curve up to 0.83 ) . Accuracy of the prediction models ranged between 80 % and 95 % in both derivation and validation cohorts , depending on the complexity of the model and the cutpoints chosen for response and nonresponse . About 80 % of patients could be predicted to be responders or nonresponders at Week 12 . Conclusion . Clinical data collected early after starting or escalating disease-modifying antirheumatic drug/biologic treatment could accurately predict LDA at 1 year in patients with early RA . For patients predicted to be nonresponders , treatment could be changed at 12 weeks to optimize outcomes OBJECTIVES To evaluate the impact of antibodies to cyclic citrullinated peptide ( ACPAs ) on radiographic progression in patients with early rheumatoid arthritis ( RA ) initially treated either with a combination of 3 disease-modifying antirheumatic drugs ( DMARDs ) or with a single DMARD .  METHODS This study included 129 patients with early active RA initially r and omised to treatment either with a combination of methotrexate , sulfasalazine , hydroxychloroquine , and prednisolone ( FIN-RACo ) ( n=69 ) or with a single DMARD ( initially sulfalasalazine ) with or without prednisolone ( SINGLE ) ( n=60 ) . After 2 years , the use of DMARDs and prednisolone became unrestricted . Radiographic progression in h and s and feet was assessed at baseline and at 1 , 2 , 3 , 4 and 5 years . ACPAs at baseline were determined with enzyme immunoassay . RESULTS ACPAs were positive in 92 ( 71 % ) patients . ACPA-positive vs. negative patients were more frequently rheumatoid factor ( RF ) positive ( 83 % vs. 22 % , p<0.001 ) and had an erosive disease ( 54 % vs. 22 % , p<0.001 ) at baseline . The presence of ACPA was associated with radiographic progression in FIN-RACo group even when the impact of RF was controlled ; the radiographic progression was remarkably slower in ACPA-negative than in ACPA-positive cases ( RF adjusted change over time between groups p=0.034 ) . In the SINGLE group , the radiographic changes progressed parallel in ACPA-negative and positive patients . CONCLUSIONS Most ACPA-positive RA patients have joint erosions already at diagnosis . ACPA positivity in early RA was related to radiographic progression even in patients treated initially with the FIN-RACo regimen . The initial FIN-RACo therapy seems to slow down the progression of joint damage in ACPA-negative patients Clinical decision making often requires estimates of the likelihood of a dichotomous outcome in individual patients . When empirical data are available , these estimates may well be obtained from a logistic regression model . Several strategies may be followed in the development of such a model . In this study , the authors compare alternative strategies in 23 small sub sample s from a large data set of patients with an acute myocardial infa rct ion , where they developed predictive models for 30-day mortality . Evaluations were performed in an independent part of the data set . Specifically , the authors studied the effect of coding of covariables and stepwise selection on discriminative ability of the result ing model , and the effect of statistical “ shrinkage ” techniques on calibration . As expected , dichotomization of continuous covariables implied a loss of information . Remarkably , stepwise selection result ed in less discriminating models compared to full models including all available covariables , even when more than half of these were r and omly associated with the outcome . Using qualitative information on the sign of the effect of predictors slightly improved the predictive ability . Calibration improved when shrinkage was applied on the st and ard maximum likelihood estimates of the regression coefficients . In conclusion , a sensible strategy in small data sets is to apply shrinkage methods in full models that include well-coded predictors that are selected based on external information This paper provides the first data on the incidence of RA  based on a prospect i ve population -based register . All new cases of inflammatory polyarthritis in the Norwich Health Authority are notified by general practitioners to the Norfolk Arthritis Register . The patients are then clinical ly evaluated by metrologists and blood taken for RF estimation . Cases of RA were defined as all those notified with an onset of symptoms in 1990 ; who presented by 31 December 1991 ; and who satisfied the 1987 ARA criteria for RA at the time of presentation . Two hundred and ten patients were notified in the defined time-frame , of whom 104 were classified as having RA . The annual incidence rate was 36/100,000 for women and 14/100,000 for men .  RA was rare in men aged under 45 yr . The incidence in men rose steeply with age . The incidence in women rose up to age 45 yr , plateaued to age 75 yr , and fell in the very elderly Golimumab is a human immunoglobulin G1κ monoclonal antibody that binds with high affinity and specificity to tumor necrosis factor-α . The objective of this study was to establish an approach for exposure-response modeling for golimumab in patients with rheumatoid arthritis using the American College of Rheumatology index of improvement ( ACRN ) as a measure of change in disease severity . Data were collected from 302 patients in the phase III GO-FORWARD trial who received golimumab or placebo plus methotrexate ( background therapy ) every 4 weeks through week 52 . A latent-variable ( unobservable ) approach was used with an inhibitory indirect response model to link the placebo ( methotrexate ) effect and golimumab concentrations to ACRN scores . A model parameterization was proposed to allow deterioration beyond baseline and maintain mechanistic interpretability of the population -based indirect response model . The modeling was conducted using a sequential pharmacokinetic/pharmacodynamic approach . None of the covariate factors evaluated ( demographics , disease characteristics , comorbidities , or concomitant medications ) significantly improved the model fits . Likelihood profiling and a bootstrap analysis were used to assess parameter estimation precision , with their suitability discussed . The approach can be readily extended to model other types of clinical ( efficacy or safety ) scores with either an upper or a lower boundary OBJECTIVE To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies ( anti-CCP ) and rheumatoid factor ( RF ) in patients with rheumatoid arthritis . METHODS 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs ( DMARD ) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks , and subsequently bimonthly , in combination with methotrexate . Serum sample s were collected at baseline and at week 24 . A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies ; RF were detected using a quantitative nephelometric assay . RESULTS At baseline , 38 of the 43 patients ( 88 % ) were positive for anti-CCP antibodies , and 41 ( 95 % ) were positive for RF . The serum titre of anti-CCP and RF decreased significantly after six months of treatment ( p = 0.0001 and p<0.0001 , respectively ) . When the patients were grouped on the basis of their clinical response to infliximab , a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement ( ACR 20 and ACR 50 ) . CONCLUSIONS Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement , suggesting that these measurements may be a useful adjunct in assessing treatment efficacy OBJECTIVE To assess plasma M-ficolin concentrations in disease-modifying antirheumatic drug (DMARD)-naive patients with early rheumatoid arthritis ( RA ) , to investigate the correlation of M-ficolin concentrations with disease activity markers , and to determine the predictive value of M-ficolin with respect to the Disease Activity Score in 28 joints ( DAS28 ) . METHODS The study group included 180 DMARD-naive patients with early RA who participated in a r and omized controlled trial of methotrexate and intraarticular glucocorticoids plus either adalimumab or placebo/adalimumab . One hundred healthy control subjects and 51 patients with chronic RA were also assessed . A s and wich-type time-resolved fluorometric immunoassay was used for quantification of plasma M-ficolin . RESULTS At baseline , M-ficolin levels were highest in the group of DMARD-naive patients with newly diagnosed active RA , and the level in these patients decreased 26 % after 1 year of aggressive treatment . The baseline M-ficolin level correlated with 5 of 7 disease activity markers , including the DAS28 and the Health Assessment Question naire ( HAQ ) , and a similar pattern of correlations was observed at 1 year . Multiple logistic regression analysis showed that an elevated M-ficolin level at baseline was the strongest predictor of not achieving either DAS28 remission ( odds ratio [ OR ] 4.18 , 95 % confidence interval [ 95 % CI ] 2.02 - 8.63 ) or low disease activity ( OR 2.45 , 95 % CI 1.13 - 5.28 ) at 1 year . The presence of a baseline M-ficolin level in the lowest quartile result ed in sensitivity of 29 % , specificity of 93 % , and positive predictive value of 95 % for low disease activity at 1 year . CONCLUSION In patients with early RA , elevated plasma M-ficolin levels correlated with a high DAS28 and a high HAQ score at baseline and 1 year . A low M-ficolin level was the strongest predictor of remission and low disease activity in a multivariate analysis We previously identified variables that predict functional disability in rheumatoid arthritis ( RA ) . Because of potential instabilities in the statistical model , we sought to determine whether these predictors were consistent across population s : 2,448 consecutive patients with ( RA ) were followed prospect ively at ARAMIS centers in Phoenix , AZ , Wichita , KS , and Saskatoon , SK . Average followup was 1.7 years in Phoenix , 3.4 years in Wichita , and 12 years in Saskatoon . Twenty-four potentially predictive variables were analyzed by stepwise linear regression . Common predictors were age , sex , and duration of illness , suggesting that these variables are important predictors of disease regardless of the population being studied . In addition , the initial level of disability and radiographic variables are good predictors of disability . Elevated erythrocyte sedimentation rate and latex titers also were associated with future functional disability but do not have a linear relationship and predict less well OBJECTIVE To determine the usefulness of a prediction model for making treatment decisions in early rheumatoid arthritis ( RA ) . METHODS In 152 patients with early RA , progression of radiological damage during the first year [ Sharp-van der Heijde ( SH ) score > 0 ] was assessed and used to define actual disease outcome . Available variables at baseline were entered in a multivariate regression analysis with progression score as dependent variable . This model was used to predict disease outcome in every patient . Using the st and ard deviations of the predicted disease outcome , patients were divided into 3 groups : ( 1 ) severe disease : high probability ( > or = 0.8 ) for progression > 0 , ( 2 ) mild disease : high probability ( > or = 0.8 ) for progression < or = 0 , and ( 3 ) not classified : no high probability for either option . It was determined how many patients could be classified by using this model . RESULTS One hundred nine patients ( 71.7 % ) showed joint damage progression during the first year . Baseline variables available were : age , sex , duration of symptoms , duration of morning stiffness , patient 's global assessment of disease activity , Health Assessment Question naire score , swollen and painful joint count , bilateral compression pain in metatarsophalangeals , rheumatoid factor positivity , erythrocyte sedimentation rate , shared epitope positivity , SH-score , and the presence of erosions . The R2 value ( approximately variation explained ) of the prediction model was 0.36 . By using this model 46.3 % of patients could be classified as having severe disease , 0 % as having mild disease , and 53.7 % could not be classified . CONCLUSION To be able to make treatment decisions in early RA based on predicted disease outcome , a better prediction of disease outcome is needed , making the search for better prognostic variables urgent Biologic drugs are effective but are also expensive , and it is difficult to evaluate the duration of treatment . Infliximab , an anti-TNFα antibody , suppresses arthritic activity and inhibits bone destruction in patients with rheumatoid arthritis ( RA ) . Here , we document that infliximab could be discontinued after clinical remission in RA patients . Among 172 patients with RA who reached clinical remission following infliximab ( 3 mg/kg ) and methotrexate ( MTX , > 6 mg/w ) , nine patients with sustained remission discontinued it . Clinical assessment was based on a disease activity score ( DAS ) that included a 28-joint count/erythrocyte sedimentation rate ( DAS28-ESR ) . The disease was assessed before and after the start of infliximab treatment , and concomitant drug treatment — in the order of corticosteroid , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and disease-modifying anti-rheumatic drugs ( DMARDs ) other than MTX — was gradually discontinued . We considered patients for discontinuation of infliximab treatment after remission ( DAS28-ESR < 2.6 ) had been sustained for more than 24 weeks . The nine patients able to discontinue treatment were all females , with a mean age of 53.8 years ; eight patients were at stage I or II .  The mean duration of disease was 28.7 months , and these patients were on corticosteroid treatment equivalent to a mean of 2.28 mg prednisolone ( PSL ) . These nine patients all met the remission st and ard — that DAS28-ESR < 2.6 for ≥24 weeks ) — and so their treatment with concomitant drugs was discontinued . After the discontinuation of infliximab , the mean period of sustained remission was 14.2 months and the longest period was 29 months . The duration of disease was significantly shorter and the points from Steinbrocker ’s stage-classification were significantly lower in the infliximab-discontinued group than in the infliximab-continued group . Strategic reductions and /or discontinuations of concomitant treatment were performed in RA patients who attained clinical remission ( DAS28 < 2.6 ) through treatment with infliximab and MTX . Nine patients successfully discontinued infliximab after maintaining clinical remission for more than 24 weeks . After infliximab was discontinued , clinical remission and suppression of joint destruction were maintained with MTX alone , especially in early RA patients OBJECTIVE To investigate sensitive ultrasonographic imaging methods for detection of synovial thickness and vascularity to discriminate between patients with early rheumatoid arthritis ( RA ) receiving infliximab + methotrexate ( MTX ) versus placebo + MTX over 18 weeks , and to compare the relationship between synovial thickening and vascularity at baseline and radiologic damage to joints of the h and s and feet at 54 weeks . METHODS Patients with early RA ( duration <3 years ) receiving stable dosages of MTX  were r and omly assigned to receive blinded infusions of 5 mg/kg infliximab ( n = 12 ) or placebo ( n = 12 ) at weeks 0 , 2 , 6 , and then every 8 weeks until week 46 . At baseline and week 18 , clinical assessment s were performed , and metacarpophalangeal joints were assessed by high-frequency ultrasonography and power Doppler ultrasonography measurements . Radiographs of the h and s and feet taken at baseline and at 54 weeks were evaluated using the van der Heijde modification of the Sharp method ( vdH-Sharp score ) . RESULTS Using changes in the total vdH-Sharp score over 54 weeks and changes in synovial thickening and joint vascularity at 18 weeks , we were able to distinguish those patients receiving infusions of infliximab + MTX from those receiving placebo + MTX . Sonographic measurements of synovial thickening and vascularity at baseline in the placebo + MTX group demonstrated clear relationships with the magnitude of radiologic joint damage at week 54 . Infliximab + MTX treatment abolished these relationships . CONCLUSION The delay or reversal of inflammatory and joint-destructive mechanisms in patients with early RA was already apparent following 18 weeks of treatment with infliximab + MTX and was reflected in radiologic changes at 54 weeks OBJECTIVE To study the impacts of 1 ) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug ( DMARD ) therapy , 2 ) two treatment strategies ( treatment with a combination of DMARDs or with a single drug ) , and 3 ) the presence of HLA-DRB1 alleles ( shared epitope ) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis ( RA ) . METHODS In the FIN-RACo ( FINnish Rheumatoid Arthritis Combination therapy ) trial , 195 patients with recent-onset RA ( median duration 6 months ) were r and omly assigned to receive either 1 ) a combination of DMARDs ( sulfasalazine , methotrexate , hydroxychloroquine , and prednisolone ) or 2 ) a single DMARD with or without prednisolone . The presence of a shared epitope was tested for in 165 of the 178 patients completing the study . The additional variables of age , sex , presence of rheumatoid factor , number of fulfilled American College of Rheumatology criteria for the classification of RA , and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years . RESULTS The delay to therapy ( cut point of 4 months ) was the only significant predictor for remission in patients treated using the single-DMARD strategy , while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy . The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short ( 0 - 4 months ) and long ( > 4 months ) delay periods ( 11 of 26 patients and 22 of 53 patients , respectively [ approximately 42 % in each group ] ) , while the corresponding frequencies in the single-DMARD group were 8 of 23 patients ( 35 % ) and 7 of 63 patients ( 11 % ) ( P = 0.021 ) . The presence of a shared epitope was not related to the induction of remission . CONCLUSION The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA OBJECTIVE To evaluate whether measurements of urinary glucosyl-galactosyl-pyridinoline ( Glc-Gal-PYD ) and urinary C-terminal crosslinking telopeptide of type II collagen ( CTX-II ) , 2 new markers of destruction of the synovium and cartilage collagen breakdown , respectively , are associated with the progression of joint damage in patients with early rheumatoid arthritis ( RA ) , and to compare this association with that with serum matrix metalloproteinase 3 ( MMP-3 ) , a proteinase expressed by synovial tissue and chondrocytes , and that with serum C-reactive protein ( CRP ) , an index of systemic inflammation . METHODS The prospect i ve study cohort comprised 116 patients with early RA who were part of a large , double-blind , r and omized study comparing the efficacy of etanercept and methotrexate .  The relationship between baseline levels of urinary Glc-Gal-PYD , urinary CTX-II , and serum MMP-3 and the progression of joint destruction , as measured by changes in the modified Sharp score ( average findings of 2 independent readers ) over 1 year , was investigated . RESULTS Levels of urinary Glc-Gal-PYD ( + 70 % ) , urinary CTX-II ( + 104 % ) , and serum MMP-3 ( + 219 % ) were elevated compared with the levels in 76 healthy controls . The baseline levels of Glc-Gal-PYD ( r = 0.30 ) , CTX-II ( r = 0.25 ) , and MMP-3 ( r = 0.29 ) correlated with the changes over 1 year in the total Sharp score ( joint space narrowing and bone erosion ) . Patients with baseline levels of Glc-Gal-PYD , CTX-II , and MMP-3 that were higher than the mean + 2 SD in healthy controls had a significantly greater progression of joint damage , with an increase in the total Sharp score over 1 year that was from 3- to 8-fold higher than that in patients with low baseline levels of these markers . Moreover , patients with these higher levels of Glc-Gal-PYD , CTX-II , and MMP-3 had a higher risk of progression of the disease ( increase in total Sharp score > or = 0.5 units ) than did the other patients ( relative risks and 95 % confidence intervals [ 95 % CI ] 3.3 [ 95 % CI 1.5 - 7.4 ] , 2.5 [ 95 % CI 1.1 - 5.7 ] , and 2.5 [ 95 % CI 1.1 - 5.6 ] , respectively ) . The baseline serum level of CRP was not significantly associated with the progression of joint damage . Adjustment of the levels of Glc-Gal-PYD , CTX-II , and MMP-3 according to radiologic damage at baseline did not alter their association with progression . After adjustment for serum CRP , the relative risk slightly decreased , but remained significant , for Glc-Gal-PYD ( 2.6 [ 95 % CI 1.1 - 6.3 ] ) . Patients with both increased levels of the molecular markers and radiologic damage at baseline had a higher risk of progression of joint damage than did those with either high molecular marker levels or radiologic damage . CONCLUSION High baseline levels of Glc-Gal-PYD , CTX-II , and MMP-3 are associated with increased risk of progression of joint destruction over 1 year in early RA . The association between baseline levels of urinary Glc-Gal-PYD and progression of joint erosion was independent of the severity of radiologic damage and inflammation at baseline . Combining the measurements of these molecular markers with radiologic assessment of joint damage may be useful for identifying patients with RA who are at high risk of rapid progression and for whom early aggressive treatment would be beneficial To investigate the initial response to treatment and risk of radiographic disease progression in current smokers ( S ) , ex‐smokers ( EX ) , and nonsmokers ( NS ) in a prospect i ve early arthritis cohort and to analyze the influence of smoking cessation on arthritis outcome We examine radiographic profile patterns using clustering algorithms to assess progression rates at set time intervals in a rheumatoid arthritis ( RA ) observational study . H and s/feet  radiographic scores  were analyzed for 190 early , seropositive RA patients with ≥ 3 radiographic observations from a prospect i ve cohort . Assessment s at 6 months , 1 year , and yearly thereafter were requested for demographic , therapeutic , functional , laboratory , radiographic , and clinical data . Progression rates for the total sharp scores [ erosion (E)+joint space narrowing ( JSN ) ] were interpolated for intervals of 0 to 6 months , 6 month-1 year , 1 - 2 years , and 2 - 3 years past first radiographic observation . Patients were grouped on their sets of rates by K-median clustering algorithms , and categorical group membership was regressed onto baseline characteristics using multinomial models . The number of clusters was determined using one-way MANOVA , and baseline differences across clusters by Kruskal-Wallis tests . The median RA duration was 6.1 months , mean age 52 years , median disease activity score ( DAS ) 4.6 , mean radiographic observations 4.6 ( range 3 - 8 ) for this mostly female ( 77 % ) , Caucasian ( 78 % ) sample . 3 patterns were determined : increasing ( n = 41 ; 22 % ) , increasing then decreasing ( n = 41 ; 22 % ) , and flat ( n = 108 ; 57 % ) . High baseline C-reactive protein was associated with a worsening radiographic progression ( p < 0.005 ) , as were HAQ-DI ( p = 0.07 ) , JSN ( p < 0.01 ) , and E ( p = 0.03 ) . Our conclusions are that radiographic progression patterns graphically supplement traditional linear rates , and are flexible to use in both clinical and observational studies . The identified clusters and rates may correspond better with clinical status and treatment over the disease course than linear progression rates alone OBJECTIVES This paper aims to evaluate if any ultrasonographic aspect of metacarpo-phalangeal ( MCP ) joint can be predictors for the development of new joint damage , at single joint level , in rheumatoid arthritis ( RA ) patients . METHODS Two hundred and forty MCP joints of 24 patients with RA were prospect ively evaluated both clinical ly and by ultrasound ( US ) at time 0 , at six months and 12 months , in order to collect the following variables : presence of synovial hypertrophy and power-Doppler ( PD ) vascularisation both grade d on a semiquantitative ( 0 - 3 ) scale , and the number and dimension of bone erosions . X-ray examinations were carried out at time 0 and at 12 months and lesions were grade d using the Sharp/van der Heijde ( S/vdH ) method at single joint level . Potential prognostic determinants for joint damage obtained at the first examination and during follow-up were entered in a conditional logistic regression analysis . RESULTS Fifteen out of seventeen ( 88 % ) of the new eroded joints on x-rays examination had persistent PD vascularity and 14/17 ( 82 % ) had persistent synovial thickening ( p=0.001 and p=0.02 , vs. non-eroded joints , respectively ) . In multiple conditional logistic regression analysis , the most important factor associated with the development of radiological joint damage was the presence of a synovial PD score ≥2 on two or more US evaluations ( OR 8.51 [ 95%CI 1.84 - 39.48 ] for Rx new erosions and OR 8.30 [ 95%CI 1.97 - 38.9 ] for increased S/vdH local joint score ) . Both baseline synovial score ≥2 and presence of Rx erosions were also significantly associated with the development of radiological joint damage . Two predictive models for x-ray erosions and total single joint level S/vdH damage score were constructed consisting of 2 baseline plus one longitudinal variable with a ROC AUC of 0.916 ( 95%CI 0.867 - 0.965 ) and 0.886 ( 95%CI 0.814 - 0.957 ) . CONCLUSIONS At the single joint level , the presence of US determined synovial thickness and PD signal at baseline and the persistent PD signal over time have relevant prognostic value for the development of articular damage in the same MCP joints of RA patients BACKGROUND New treatment strategies for early rheumatoid arthritis are evolving rapidly . We aim ed to compare addition of conventional disease-modifying antirheumatic drugs ( sulfasalazine and hydroxychloroquine ) with addition of a tumour necrosis factor antagonist ( infliximab ) to methotrexate in patients with early rheumatoid arthritis . METHODS We undertook a r and omised trial in 15 rheumatology units in Sweden . We enrolled patients with early rheumatoid arthritis ( symptom duration < 1 year ) and administered methotrexate ( up to 20 mg per week ) . After 3 - 4 months , those who had not achieved low disease activity but who could tolerate methotrexate were r and omly allocated by computer addition of either sulfasalazine and hydroxychloroquine or infliximab . Primary outcome was achievement of a good response according to European League Against Rheumatism ( EULAR ) criteria at 12 months . Patients were followed up to 24 months ; here , we present findings at 12 months . Analysis was by intention to treat and we used non-responder imputation . The Swefot ( Swedish Pharmacotherapy ) study is registered in the WHO data base at the Karolinska University Hospital , number CT20080004 . FINDINGS 487 patients were initially enrolled . Of 258 who had not achieved low disease activity with methotrexate  , 130 were allocated sulfasalazine and hydroxychloroquine and 128 were assigned infliximab . 32 of 130 ( 25 % ) patients allocated sulfasalazine and hydroxychloroquine achieved the primary outcome compared with 50 of 128 ( 39 % ) assigned infliximab ( risk ratio 1.59 [ 95 % CI 1.10 - 2.30 ] , p=0.0160 ) . Adverse events were balanced fairly well between the two groups and accorded with known adverse events of the drugs used . No deaths occurred in either group . INTERPRETATION In patients with early rheumatoid arthritis in whom methotrexate treatment failed , addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinical ly superior to addition of conventional disease-modifying antirheumatic drugs . FUNDING Swedish Rheumatism Association , Schering-Plough OBJECTIVE To develop a clinical model for the prediction , at the first visit , of 3 forms of arthritis outcome : self-limiting , persistent nonerosive , and persistent erosive arthritis . METHODS A st and ardized diagnostic evaluation was performed on 524 consecutive , newly referred patients with early arthritis . Potentially diagnostic determinants obtained at the first visit from the patient 's history , physical examination , and blood and imaging testing were entered in a logistic regression analysis .  Arthritis outcome was recorded at 2 years ' followup . The discriminative ability of the model was expressed as a receiver operating characteristic ( ROC ) area under the curve ( AUC ) . RESULTS The developed prediction model consisted of 7 variables : symptom duration at first visit , morning stiffness for > or = 1 hour , arthritis in > or =3 joints , bilateral compression pain in the metatarsophalangeal joints , rheumatoid factor positivity , anti-cyclic citrullinated peptide antibody positivity , and the presence of erosions ( h and s/feet ) . Application of the model to an individual patient result ed in 3 clinical ly relevant predictive values : one for self-limiting arthritis , one for persistent nonerosive arthritis , and one for persistent erosive arthritis . The ROC AUC of the model was 0.84 ( SE 0.02 ) for discrimination between self-limiting and persistent arthritis , and 0.91 ( SE 0.02 ) for discrimination between persistent nonerosive and persistent erosive arthritis , whereas the discriminative ability of the American College of Rheumatology 1987 classification criteria for rheumatoid arthritis was significantly lower , with ROC AUC values of 0.78 ( SE 0.02 ) and 0.79 ( SE 0.03 ) , respectively . CONCLUSION A clinical prediction model was developed with an excellent ability to discriminate , at the first visit , between 3 forms of arthritis outcome . Validation in other early arthritis clinics is necessary BACKGROUND Etanercept , which blocks the action of tumor necrosis factor , reduces disease activity in patients with long-st and ing rheumatoid arthritis . Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown . METHODS We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept  ( 10 or 25 mg ) or weekly  oral methotrexate ( mean , 19 mg per week ) for 12 months . Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology . Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale . On this scale , an increase of 1 point represents one new erosion or minimal narrowing . RESULTS As compared with patients who received methotrexate , patients who received the 25-mg dose of etanercept had a more rapid rate of improvement , with significantly more patients having 20 percent , 50 percent , and 70 percent improvement in disease activity during the first six months ( P<0.05 ) . The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group ( P= 0.001 ) , and the respective increases during the first 12 months were 0.47 and 1.03 ( P=0.002 ) . Among patients who received the 25-mg dose of etanercept , 72 percent had no increase in the erosion score , as compared with 60 percent of patients in the methotrexate group ( P=0.007 ) . This group of patients also had fewer adverse events ( P=0.02 ) and fewer infections ( P= 0.006 ) than the group that was treated with methotrexate . CONCLUSIONS As compared with oral methotrexate , subcutaneous [ corrected ] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis OBJECTIVE Because available biomarkers ( rheumatoid factors [ RF ] , anti-cyclic citrullinated autoantibodies [ anti-CCP2 ] , erythrocyte sedimentation rate at 1st hour [ESR]/C-reactive peptide [ CRP ] and bone erosions ) are insufficient to predict rheumatoid arthritis ( RA ) structural damage , to determine whether synovium expression of greater or equal to 1 markers could constitute new prognostic factor(s ) . METHOD The study was conducted on 18 prospect ively enrolled disease-modifying anti-rheumatic drug (DMARD)- and glucocorticoid-naïve , VErA cohort patients with very-early arthritis ( median duration : 4months ) . Recorded at baseline were : clinical and biological ( serum ESR , CRP , RF-isotypes , anti-CCP2 , osteoprotegerin , receptor activator of nuclear κB-lig and [ RANK-L ] and cartilage oligomeric matrix protein [ COMP ] levels ) data ; synovium expression ( HLA-DR , CD163 , CD3 , CD20 , VEGF , osteoprotegerin , RANK-L , Bcl2 and global inflammation index ) for a metacarpophalangeal joint-synovium biopsy . Baseline and 3-year h and - and -foot X-rays were grade d with the van der Heijde-modified-Sharp score ; the judgment criterion was its progression during follow-up . Pearson 's product moment correlation statistics were used to test for association between paired sample s. RESULTS A baseline , a significant relationship was found between erosive damage and markers of B-cell activation , notably the synovium CD20 expression ( r=0.68 ; P=0.0001 ) . Quantified by the modified-Sharp erosion score variation , the 3-year structural damage progression was significantly correlated with : serum levels of RF-IgG ( r=0.75 ; P=0.0003 ) , -IgM ( r=0.69 ; P=0.001 ) , anti-CCP2 ( r=0.53 ; P=0.02 ) and RANK-L ( r=0.61 ; P=0.007 ) ; synovium CD20 expression ( r=0.70 ; P=0.001 ) . CONCLUSION This analysis of the prognostic value of a large panel of synovium markers in a limited sample of prospect ively followed , well-documented patients suggested that both synovial CD20 and serum RANK-L levels might be new predictors of structural damage progression in very-early RA OBJECTIVES To identify factors associated with poor physical function in rheumatoid arthritis and to assess whether baseline joint damage has an impact on improvement in physical function during infliximab treatment . METHODS 428 patients with active rheumatoid arthritis despite methotrexate treatment received methotrexate alone or with infliximab ( 3 mg/kg or 10 mg/kg every four or eight weeks ) for 54 weeks ( the ATTRACT trial ) . Data on clinical outcomes and physical function ( assessed by the health assessment question naire ( HAQ ) ) were collected . Structural damage was assessed using the van der Heijde modification of the Sharp score . Odds ratios ( OR ) for factors associated with severe functional disability ( HAQ > or = 2.0 ) at baseline were estimated using multiple logistic regression analyses , and baseline factors related to the change in physical function after treatment at week 54 were determined . RESULTS Baseline radiographic scores were correlated with baseline HAQ scores . After adjustment for demographic characteristics in the logistic regression model , baseline disease activity scores , radiological joint damage , fatigue , and morning stiffness were found to be associated with severe functional disability ( HAQ > 2.0 ) , with OR values of 2.00 ( 1.53 to 2.63 ) , 1.82 ( 1.15 to 2.87 ) , 1.19 ( 1.05 to 1.34 ) , and 1.07 ( 1.01 to 1.13 ) , respectively . In multiple linear regression analysis , physical disability , joint damage , and fatigue at baseline were correlated with less improvement in physical function after treatment . Infliximab treatment was associated with greater improvement in physical function . CONCLUSIONS Greater joint damage at baseline was associated with poorer physical function at baseline and less improvement in physical function after treatment , underlining the importance of early intervention to slow the progression of joint destruction In terms of the relationship between synovial inflammation and radiographic changes , including both joint damage repair and progression,1 in rheumatoid arthritis ( RA ) , pre-existing joint damage and persistent synovitis may promote joint destruction , while in the absence of synovitis , damaged joints may heal.2 , 3 Although presentation of radiographic results using cumulative probability plots has substantially improved underst and ing of clinical trial data , 4 the effects of treatments on radiographic progression and improvement ( regression ) in individual RA patients has not yet been fully explained . In the JESMR study , 5 , 6 151 active RA patients unresponsive to treatment with methotrexate ( MTX ) were r and omised into 1 of 2 treatment groups : etanercept ( ETN ) 50 mg/week with 6–8 mg/week of MTX ( the E+M group ) , or ETN alone ( the E group ) . Radiographs of the h and s and feet before ETN ( baseline ) and during the first year of treatment were available from 53 ( 72 % ) and 68 ( 88 % ) patients in the E and E+M groups , respectively . Baseline characteristics of patients were comparable between those with and without available radiographic data in each treatment group ( data not shown ) . However , most patients without data did not complete the study up to Week 52 as per protocol , chiefly due to lack of efficacy in the E group.6 The mean baseline total Sharp-van der Heijde score (TSS)7 was 114.5 in the E group and 113.1 in the E+M PURPOSE To compare the effect of delayed and early treatment strategies on disease outcome in patients with rheumatoid arthritis . SUBJECTS AND METHODS Between 1993 and 1995 , 109 patients diagnosed with probable or definite rheumatoid arthritis of recent onset were initially treated with analgesics ; if they had persistent active disease , they were treated subsequently with the disease-modifying drugs chloroquine or salazopyrine ( delayed treatment ) .  Between 1996 and 1998 , similar patients ( n = 97 ) were promptly treated with either chloroquine or salazopyrine ( early treatment ) . RESULTS The median lag to the initiation of disease-modifying treatment was 15 days in the early treatment group and 123 days in the delayed treatment group . There was less radiologic joint damage after 2 years in the early treatment group ( median Sharp score , 3.5 ; 95 % confidence interval [ CI ] : 1 to 7 ) compared with the delayed treatment group ( median Sharp score , 10 ; 95 % CI : 5 to 15 ; P < 0.05 ) . The median area under the curve of the 2-year disease activity score was lower in the early treatment group ( 64 units ; 95 % CI : 59 to 69 units ) compared with the delayed treatment group ( 73 units ; 95 % CI : 69 to 77 units ; P = 0.002 ) . CONCLUSION In this nonr and omized comparison , early introduction of disease-modifying antirheumatic drugs was associated with a better disease outcome after 2 years BACKGROUND Neutralization of tumor necrosis factor a ( TNF-alpha ) for three to six months reduces the symptoms and signs of rheumatoid arthritis . However , the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known . METHODS We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab , a chimeric monoclonal antibody against TNF-alpha  , in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks . We assessed clinical responses with use of the criteria of the American College of Rheumatology , the quality of life with a health-status question naire , and the effect on joint damage radiographically . RESULTS The combination of infliximab and methotrexate was well tolerated and result ed in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone ( clinical response , 51.8 percent vs. 17.0 percent ; P<0.001 ) . The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone . Radiographic evidence of joint damage increased in the group given methotrexate , but not in the groups given infliximab and methotrexate ( mean change in radiographic score , 7.0 vs. 0.6 , P<0.001 ) . Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response . CONCLUSIONS In patients with persistently active rheumatoid arthritis despite methotrexate therapy , repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage OBJECTIVE To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis ( RA ) . METHODS One hundred thirty-two patients with early RA were treated with nonbiologic therapies for 2 years and studied longitudinally . Genomic DNA was analyzed for presence of the shared epitope . Levels of matrix metalloproteinases ( matrix metalloproteinase 1 [ MMP-1 ] , MMP-13 , and MMP-3 ) , tissue inhibitor of metalloproteinases 1 ( TIMP-1 ) , and cartilage oligomeric matrix protein ( COMP ) were assessed in serially obtained serum sample s. The presence of pyridinoline ( Pyr ) , deoxypyridinoline , glycosylated Pyr ( Glc-Gal-Pyr ) , and C-telopeptide of type II collagen ( CTX-II ) was assessed in urine sample s. Radiographs obtained at entry and at 2 years were evaluated using the modified Larsen score . RESULTS Baseline and 2-year radiographs were available from 118 patients .  Larsen scores worsened during the 2 years in 50 patients , while 68 patients had no radiographic progression . Levels of a variety of biochemical markers , i.e. , MMP-3 , CTX-II , COMP , TIMP-1 , Pyr , and Glc-Gal-Pyr , correlated significantly with radiographic progression at entry and longitudinally as assessed by area under the curve ( AUC ) . By multivariate analysis , a model including MMP-3 and CTX-II was identified as providing the best prediction of radiographic progression at entry ( predictive accuracy by receiver operating characteristic [ ROC ] AUC = 0.76 [ 95 % confidence interval 0.66 - 0.85 ] ) , while a combination of MMP-3 , CTX-II , and swollen joint count formed the best longitudinal AUC model ( predictive accuracy by ROC AUC = 0.81 [ 95 % confidence interval 0.73 - 0.89 ] ) . Patient-reported measures ( Health Assessment Question naire , pain scores ) were of limited use . In a subset of 50 patients who were treated with methotrexate ( MTX )  during the followup period , median serum MMP-3 levels decreased after the initiation of MTX therapy ( P = 0.0003 ) . CONCLUSION These results indicate that biochemical markers are useful predictors of radiographic progression in RA and that serum MMP-3 levels decrease significantly with MTX therapy . Multivariate models that include MMP-3 and CTX-II perform better than existing traditional markers in predicting radiographic outcome in RA OBJECTIVE To evaluate the effectiveness and safety of anti-tumor necrosis factor ( anti-TNF ) therapies in rheumatoid arthritis ( RA ) , and to identify the factors involved in this response . METHODS Dynamic prospect i ve cohort study of patients with RA treated with anti-TNF under clinical practice conditions .  Effectiveness was evaluated using Disease Activity Score ( DAS ) 28 , European League Against Rheumatism ( EULAR ) response , Health Assessment Question naire ( HAQ ) , and time to treatment failure . Prior adherence was evaluated retrospectively and safety was evaluated by adverse events ( AE ) . The analysis was restricted to anti-TNF-naive patients . RESULTS The study included 161 patients treated for RA during 6 years ( 60 infliximab , 79 etanercept , and 22 adalimumab ) . At 6 months , 15 % reached a good EULAR response and 38 % a moderate response . A mean decrease of -1.5 ( p < 0.0001 ) was observed in the DAS28 and of -0.34 in the HAQ ( p < 0.0001 ) ; however , women showed poorer progress in terms of DAS and HAQ . In the first year , 64.3 % did not experience treatment failure and this figure was 50.5 % after 2 years . In one-third , glucocorticoids were withdrawn and in the remainder the dose was reduced by 50 % . Adherence to treatment , selection of etanercept , and intensification of infliximab were associated with a lower probability of premature failure in the multivariate model . AE were similar to other those in studies and no outst and ing differences in safety were found between the 3 anti-TNF therapies . CONCLUSIONS Anti-TNF treatments are effective and safe , reducing the activity of the disease , disability , and the need for corticosteroids . Patients who displayed good adherence prior to the anti-TNF treatment and were treated with etanercept or with increasing doses of infliximab had the best chance of displaying a response OBJECTIVE To assess whether it is better to intensively treat all patients with early rheumatoid arthritis ( RA ) using combinations of drugs or to reserve this approach for patients who do not have an appropriate response ( as determined by a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [ DAS28-ESR ] of ≥ 3.2 at week 24 )  to methotrexate ( MTX ) monotherapy , and to assess whether combination therapy with MTX plus etanercept is superior to the combination of MTX plus sulfasalazine plus hydroxychloroquine . METHODS The Treatment of Early Aggressive Rheumatoid Arthritis ( TEAR ) study is a 2-year , r and omized , double-blind trial . A 2 × 2 factorial design was used to r and omly assign subjects to 1 of 4 treatment arms : immediate treatment with MTX plus etanercept , immediate oral triple therapy ( MTX plus sulfasalazine plus hydroxychloroquine ) , or step-up from MTX monotherapy to one of the combination therapies ( MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine ) at week 24 if the DAS28-ESR was ≥ 3.2 . All treatment arms included matching placebos . The primary outcome was an observed-group analysis of DAS28-ESR values from week 48 to week 102 . RESULTS At week 24 ( beginning of the step-up period ) , subjects in the 2 immediate-treatment groups demonstrated a greater reduction in the DAS28-ESR compared with those in the 2 step-up groups ( 3.6 versus 4.2 ; P < 0.0001 ) ; no differences between the combination-therapy regimens were observed . Between week 48 and week 102 , subjects r and omized to the step-up arms had a DAS28-ESR clinical response that was not different from that of subjects who initially received combination therapy , regardless of the treatment arm . There was no significant difference in the DAS28-ESR between subjects r and omized to oral triple therapy and those r and omized to receive MTX plus etanercept . By week 102 , there was a statistically significant difference in the change in radiographic measurements from baseline between the group receiving MTX plus etanercept and the group receiving oral triple therapy ( 0.64 versus 1.69 ; P = 0.047 ) . CONCLUSION There were no differences in the mean DAS28-ESR during weeks 48 - 102 between subjects r and omized to receive MTX plus etanercept and those r and omized to triple therapy , regardless of whether they received immediate combination treatment or step-up from MTX monotherapy . At 102 weeks , immediate combination treatment with either strategy was more effective than MTX monotherapy prior to the initiation of step-up therapy . Initial use of MTX monotherapy with the addition of sulfasalazine plus hydroxychloroquine ( or etanercept , if necessary , after 6 months ) is a reasonable therapeutic strategy for patients with early RA . Treatment with the combination of MTX plus etanercept result ed in a statistically significant radiographic benefit compared with oral triple therapy Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis ( RA ) in remission . Objective The trial aims to compare the effect of progressive spacing of TNF-blocker injections ( S-arm ) to their maintenance ( M-arm ) for established patients with RA in remission . Methods The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year , patients in remission on 28-joint Disease Activity Score ( DAS28 ) for ≥6 months and patients with stable joint damage . Patients were r and omised into two arms : maintenance or injections spacing by 50 % every 3 months up to complete stop . Spacing was reversed to the previous interval in case of relapse , and eventually reattempted after remission was reachieved . The primary outcome was the st and ardised difference of DAS28 slopes , based on a linear mixed-effects model ( equivalence interval set at ±30 % ) . Results 64 and 73 patients were included in the S-arm and M-arm , respectively , which was less than planned . In the S-arm , TNF blockers were stopped for 39.1 % , only tapered for 35.9 % and maintained full dose for 20.3 % . The equivalence was not demonstrated with a st and ardised difference of 19 % ( 95 % CI −5 % to 46 % ) . Relapse was more common in the S-arm ( 76.6 % vs 46.5 % , p=0.0004 ) . However , there was no difference in structural damage progression . Conclusions Tapering was not equivalent to maintenance strategy , result ing in more relapses without impacting structural damage progression . Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings . Trial registration number : Clinical Trials.gov : NCT00780793 ; EudraCT identifier : 2007 - 004483 - 41 Objectives To assess which treatment strategy is most effective in inducing remission in early ( rheumatoid ) arthritis . Methods 610 patients with early rheumatoid arthritis ( RA 2010 criteria ) or undifferentiated arthritis ( UA ) started treatment with methotrexate ( MTX ) and a tapered high dose of prednisone . Patients in early remission ( Disease Activity Score < 1.6 after 4 months ) tapered prednisone to zero and those with persistent remission after 8 months , tapered and stopped MTX . Patients not in early remission were r and omised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone ( arm 1 ) or to MTX plus adalimumab ( ADA ) ( arm 2 ) . If remission was present after 8 months both arms tapered to MTX monotherapy ; if not , arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA .  Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA . Results 375/610 ( 61 % ) patients achieved early remission . After 1 year 68 % of those were in remission and 32 % in drug-free remission . Of the r and omised patients , 25 % in arm 1 and 41 % in arm 2 achieved remission at year 1 ( p<0.01 ) . Outcomes were comparable between patients with RA and those with UA . Conclusions Initial MTX and prednisone result ed in early remission in 61 % of patients with early ( rheumatoid ) arthritis . Of those , 68 % were in remission and 32 % were in drug-free remission after 1 year . In patients not in early remission , earlier introduction of ADA result ed in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone Objectives To develop a matrix model for the prediction of rapid radiographic progression ( RRP ) in sub population s of patients with recent-onset rheumatoid arthritis ( RA ) receiving different dynamic treatment strategies . Methods Data from 465 patients with recent-onset RA r and omised to receive initial monotherapy or combination therapy were used . Predictors for RRP ( increase in Sharp-van der Heijde score ≥5 after 1 year ) were identified by multivariate logistic regression analysis . For sub population s , the estimated risk of RRP per treatment group and the number needed to treat ( NNT ) were visualised in a matrix . Results The presence of autoantibodies , baseline C-reactive protein ( CRP ) level , erosion score and treatment group were significant independent predictors of RRP in the matrix . Combination therapy was associated with a markedly reduced risk of RRP . The positive and negative predictive values of the matrix were 62 % and 91 % , respectively . The NNT with initial combination therapy to prevent one patient from RRP with monotherapy was in the range 2–3 , 3–7 and 7–25 for patients with a high , intermediate and low predicted risk , respectively . Conclusion The matrix model visualises the risk of RRP for sub population s of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy . Rheumatologists might use the matrix for weighing their initial treatment choice OBJECTIVE To study prospect ively the daily practice effectiveness of a step-down early rheumatoid arthritis ( RA ) treatment strategy . METHODS Patients with severe RA and no contra-indications were proposed step-down therapy , the others step-up . Step-down patients received a modified combination therapy in early RA ( COBRA ) regimen : sulphasalazine ( SPS ) , 2 g daily , and methotrexate ( MTX ) , 15 mg weekly , combined with step-down oral prednisolone ( start 60 mg daily , fast tapering to 7.5 mg over 6 weeks , discontinuation from week 28 ) . At week 40 , patients were r and omized to maintenance therapy with either SPS or MTX if disease activity score-28 ( DAS28 ) was acceptably low . The step-up group started disease-modifying anti-rheumatic drug ( DMARD ) monotherapy . In both groups , treatment was adjusted at follow-up , based on DAS28 . DAS28 , functionality Health Assessment Question naire ( HAQ ) , adverse events , DMARD changes and steroid use were registered 4-monthly for 2 yrs . RESULTS Nineteen patients received step-down and 52 step-up treatment . More patients completed the first year without unplanned DMARD changes and without dosage adjustment and fewer had DMARD changes due to side effects or inefficacy in the step-down group compared with step-up , whereas the number of adverse events was comparable . MTX proved to be the most effective maintenance therapy after step-down . The DAS response , proportion of patients in remission , HAQ response and proportion of patients without disability at 4 months was higher in the step-down group . CONCLUSIONS In daily practice , a step-down treatment strategy for early RA is more effective than a step-up approach OBJECTIVE To investigate the effect of adalimumab treatment on anti-cyclic citrullinated peptide antibodies ( anti-CCP ) in patients with rheumatoid arthritis ( RA ) . METHODS 70 RA patients who failed treatment with disease modifying antirheumatic drugs ( DMARDs ) received 40 mg adalimumab subcutaneously every other week during 24 weeks . Serum sample s were collected at baseline and at weeks 8 , 16 and 24 before the corresponding adalimumab dose . The serum anti-CCP levels were tested by enzyme linked immunosorbent assay . RESULTS At baseline , 52 of the 70 patients ( 74.3 % ) were positive for anti-CCP antibodies . 60 % of the anti CCP positive patients and 44.4 % of the anti CCP negative patients were ACR 20 responders at week 24 ( p<0.049 ) . The serum levels of anti-CCP antibodies decreased significantly after 24 weeks of adalimumab treatment only in those patients who met ACR 20 response criteria at week 24 ( p<0.00044 ) . Differences between baseline anti-CCP titers and those at 8 , 16 and 24 weeks were all statistically significant ( p<0.014 , 0.003 and 0.019 respectively ) . No statistically significant changes in the anti-CCP levels were observed in patients who did not meet the ACR 20 response criteria . CONCLUSION Basal anti-CCP antibodies levels correlate with clinical response to adalimumab . A decrease in anti-CCP levels on time was observed in patients showing also clinical improvement , suggesting that serum anti-CCP antibodies determination may be useful in assessing treatment efficacy in RA patients OBJECTIVE To assess the prevalence , relationship between and predictors of clinical and imaging remission in early RA , achieved with treat-to-target management in clinical practice . METHODS A prospect i ve observational study was conducted in patients with new-onset RA . The treatment target was remission by DAS28-CRP < 2.6 . Twelve-month outcomes included DAS28-CRP remission , DAS44-CRP remission , ACR/EULAR Boolean remission ( BR ) and absent or absent/minimal power Doppler activity ( PDA ) on US of 26 joints ( total PDA score = 0 or ⩽1 , respectively ) . Logistic regression was conducted to identify baseline predictors of these outcomes . RESULTS Of 105 patients with complete 12-month data , the rate of DAS28-CRP remission was 43 % , DAS44-CRP remission was 39 % , BR was 14 % , absent PDA was 40 % and absent/minimal PDA was 57 % . Among patients achieving clinical remission defined by DAS28-CRP , DAS44-CRP or BR , absence of PDA was observed in 42 , 44 and 40 % , respectively ; absent/minimal PDA was detected in 62 , 66 and 67 % , respectively . On multivariable analysis , shorter symptom duration , male gender , fewer tender joints and lower disability were associated with the clinical remission definitions . Lack of OA predicted absence of PDA , and lower total baseline PDA predicted absent/minimal PDA . CONCLUSION DAS28-CRP remission and absence of PDA were observed in almost half of the patients , but less than a quarter achieved both . Achievement of BR was rare . The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis , with implication s for treat-to-target management . Long-term follow-up should determine the most appropriate target UNLABELLED OBJECTIVE ; Several factors predict joint damage in early rheumatoid arthritis ( RA ) . In the context of a trial in early RA , we studied the relationship between clinical signs in individual joints and their propensity to develop progressive damage . METHODS The COBRA ( Combinatietherapie Bij Reumatoide Artritis ) multicenter trial compared the efficacy of prednisolone , methotrexate , and sulfasalazine against sulfasalazine alone in 155 patients with early RA . Two blinded observers interpreted radiographs in sequence ( using the Sharp/Van der Heijde scoring system ) ; in each center , one blinded observer performed clinical assessment s every 3 months . The current analysis is based on clinical and radiologic data of the individual metacarpophalangeal ( MCP ) and proximal interphalangeal ( PIP ) joints of 135 patients . Conditional stepwise logistic regression analyzed the relationship between damage ( progression ) and clinical signs at baseline and followup for each of these joints individually in each patient . RESULTS Combination therapy strongly retarded the progression of damage . Progression was stronger in patients with rheumatoid factor , HLA-DR4 , and high levels of disease activity at baseline . At baseline , 6 % of the MCP and PIP joints showed damage ; after 1 year , disease had progressed in 10 % of these joints . Baseline damage , swelling , or pain in a joint independently and strongly predicted the progression of damage in that joint ( P < 0.001 ) . Each additional point in the swelling score ( range 0 - 2 ) tripled the risk for subsequent progression . Each additional point on the Sharp scale ( range 0 - 8 per joint ) and each additional point on the pain scale ( range 0 - 3 ) doubled the risk . The mean pain and swelling scores over the year were even stronger predictors of damage . CONCLUSION Local expression of early RA disease activity , both at baseline and at 1-year followup , is strongly related to progression of damage in the individual joint OBJECTIVE To evaluate drug adherence , clinical response and predictors thereof for tocilizumab in patients with RA in routine care based on prospect ively collected data from the Swedish biologics register , Anti-Rheumatic Therapies in Sweden . METHODS RA patients who had started with tocilizumab from September 2008 until March 2012 were identified . Cox regression and logistic regression models were used . RESULTS A total of 530 RA patients were included , of whom 80.6 % were female , 64.7 % were on concomitant DMARDs , of which 300 were on MTX and 12 % were biologic naive . The overall 6 month , 1 and 2 year estimated drug continuations were 79 % , 64 % and 50 % , respectively . In the multivariate analyses , a low initial level of CRP [ hazard ratio ( HR ) 0.76/1 S.D. ( 95 % CI 0.63 , 0.91 ) ] , high HAQ score [ HR 1.23/1 S.D. ( 95 % CI 1.06 , 1.44 ) ] and prior exposure to different biologics [ HR 1.43 ( 95 % CI 1.12 , 1.83 ) ] were predictors for drug termination , whereas concomitant DMARD therapy was not . European League Against Rheumatism ( EULAR ) good , moderate , and no response were achieved by 184 ( 46.7 % ) , 133 ( 33.8 % ) and 77 ( 19.5 % ) patients , respectively . Predictors for EULAR good response vs no response ( at 2.5 - 8 months ) were low HAQ [ odds ratio ( OR ) 0.56/1 S.D. ( 95 % CI 0.40 , 0.78 ) ] , high 28-joint DAS [ OR 2.0/1 S.D. ( 95 % CI 1.44 , 2.78 ) ] and not being on prednisolone [ OR 0.47 ( 95 % CI 0.25 , 0.88 ) ] at baseline . CONCLUSION In this RA cohort treated with tocilizumab , the estimated 1 year drug continuation was 64 % and 80 % of the patients achieved a EULAR response . Drug discontinuation was not predicted by no concomitant DMARD , but by low CRP , high HAQ and prior exposure to biologics Objective Anticitrullinated protein antibodies ( ACPAs ) are suggested to identify different subsets of patients with rheumatoid arthritis ( RA ) . The authors compared the clinical and radiological responses to Disease Activity Score (DAS)-steered treatment in patients with RA positive or RA negative for ACPA . Methods In the Beh and elStrategieën ( BeSt ) study , 508 patients with recent-onset RA were r and omised to four treatment strategies aim ed at a DAS ≤2.4 . Risks of damage progression and ( drug-free ) remission in 8 years were compared for ACPA-positive and ACPA-negative patients using logistic regression analysis . Functional ability and DAS components over time were compared using linear mixed models . Results DAS reduction was achieved similarly in ACPA-positive and ACPA-negative patients in all treatment strategy groups , with a similar need to adjust treatment because of inadequate response . Functional ability and remission rates were not different for ACPA-positive and ACPA-negative patients . ACPA-positive patients had more radiological damage progression , especially after initial monotherapy . They had a lower chance of achieving ( persistent ) drug-free remission . Conclusion Clinical response to treatment was similar in ACPA-positive and ACPA-negative patients . However , more ACPA-positive patients , especially those treated with initial monotherapy , had significant radiological damage progression , indicating that methotrexate monotherapy and DAS- ( ≤2.4 ) steered treatment might be insufficient to adequately suppress joint damage progression in these patients We conducted a two-year prospect i ve study to clarify the efficacy of infliximab at improving the health assessment question naire ( HAQ ) score and associated factors in 67 patients with advanced rheumatoid arthritis ( RA ) . All patients were scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0 , 2 , 6 and every eight weeks thereafter through to week 102 , and were fully examined at the time of each infusion . Parameters of disease activity such as the serum level of C-reactive protein ( CRP ) , the serum level of matrix metalloproteinase-3 ( MMP-3 ) and the 28-joint disease activity score ( DAS28 ) were obtained , and the functional capabilities of the patients were assessed using the HAQ score . The serum CRP , the MMP-3 , the DAS28(CRP ) level , and the mean HAQ score decreased rapidly at two weeks after the start of infliximab treatment ( CRP from 3.7 to 0.9 mg/dl , MMP-3 from 362.3 to 192.8 ng/ml , DAS28(CRP ) from 5.6 to 3.7 , and HAQ score from 1.5 to 0.9 ) . Compared with the baseline values , the mean progression of the modified van der Heijde (vdH)–Sharp score after one year was 4.4 ± 5.8 ( median : 3.0 ) , and that after two years was 3.1 ± 6.9 ( median : 1.0 ) . A 93 % reduction in the rate of joint destruction , as measured using the vdH – Sharp score , was estimated after infliximab therapy . Patients with less joint damage ( shorter disease duration or lower vdH – Sharp score ) regained more of their daily activities . The present study demonstrated the importance of activity control before the progression of irreversible factors , such as joint destruction , for maintaining the functional capacities of RA patients Objective . To evaluate the diagnostic accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism ( ACR/EULAR ) and 1987 ACR criteria for rheumatoid arthritis ( RA ) , and the respective role of the algorithm and scoring of the ACR/EULAR . Methods . In total , 270 patients with recent-onset arthritis of < 1 year duration were included prospect ively between 1995 and 1997 and followed for 2 years . RA was defined as the combination , at completion of followup , of RA diagnosed by an office-based rheumatologist and treatment with a disease-modifying antirheumatic drug or glucocorticoid . We compared the sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) of the criteria sets in the overall population , in the subgroup meeting the tree condition for ACR/EULAR scoring , and in the overall population classified according the full tree . Results . At baseline , 111 of the 270 patients had better alternative diagnoses and 16 had erosions typical for RA ; of the 143 remaining patients , 52 had more than 6 ACR/EULAR 2010 points ( indicating definite RA ) and 91 had fewer than 6 points . After 2 years , 11/16 patients with erosions and 40/52 with more than 6 points had RA . 100 of the 270 patients met the reference st and ard for RA . Sensitivity , specificity , PPV , and NPV of the ACR/EULAR ( full tree ) were 51/100 ( 51 % ) , 153/170 ( 90 % ) , 51/68 ( 75.4 % ) , and 153/202 ( 75.7 % ) , respectively . Diagnostic accuracies of the ACR/EULAR score and ACR 1987 criteria were not statistically different . Conclusion . Much of the improvement of the ACR/EULAR criteria was ascribable to the use of exclusion criteria in the algorithm Objective . We conducted a longitudinal observational study of biological disease-modifying antirheumatic drugs ( bDMARD ) to describe the proportions of patients with rheumatoid arthritis in remission who discontinued these agents , and to assess the potential predictors of the decision to discontinue . Methods . We used data from the US COnsortium of Rheumatology Research ers Of North America ( CORRONA ) and the Japanese National Data base of Rheumatic Diseases by iR-net in Japan ( NinJa ) registries , and ran parallel analyses . Patients treated with bDMARD who experienced remission ( defined by the Clinical Disease Activity Index ≤ 2.8 ) were included . The outcome of interest was the occurrence of bDMARD discontinuation while in remission . The predictors of discontinuation were assessed in the Cox regression models . Frailty models were also used to examine the effects of individual physicians in the discontinuation decision . Results . The numbers of eligible patients who were initially in remission were 6263 in the CORRONA and 744 in the NinJa . Among these patients , 10.0 % of patients in CORRONA and 11.8 % of patients in NinJa  discontinued bDMARD  while in remission over 5 years , whereas many of the remaining patients lost remission before discontinuing bDMARD . Shorter disease duration was associated with higher rates of discontinuation in both cohorts . In CORRONA , methotrexate use and lower disease activity were also associated with discontinuation . In frailty models , physician r and om effects were significant in both cohorts . Conclusion . Among patients who initially experienced remission while receiving bDMARD , around 10 % remained in remission and then  discontinued bDMARD in both registries . Several factors were associated with more frequent discontinuation while in remission . Physician preference likely is also an important correlate of bDMARD discontinuation , indicating the need for st and ardization of practice
BACKGROUND Rheumatoid arthritis ( RA ) is a chronic , debilitating disease associated with reduced quality of life and substantial costs .
It is unclear which tests and assessment tools allow the best assessment of prognosis in people with early RA and whether or not variables predict the response of patients to different drug treatments .
OBJECTIVE To systematic ally review evidence on the use of selected tests and assessment tools in patients with early RA ( 1 ) in the evaluation of a prognosis ( review 1 ) and ( 2 ) as predictive markers of treatment response ( review 2 ) .