Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab bef Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study) A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial Expression of soluble CD83 in plasma from early‐stage rheumatoid arthritis patients is not modified by anti‐TNF‐&agr; therapy Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis. Soluble CD206 plasma levels in rheumatoid arthritis reflect decrease in disease activity Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naïve patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study. Effectiveness of four dynamic treatment strategies in patients with anticitrullinated protein antibody-negative rheumatoid arthritis: a randomised trial Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression Evaluation of two strategies (initial methotrexate monotherapy vs its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial. Relationship of patient-reported outcomes with MRI measures in rheumatoid arthritis Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study) Effect of the early use of the anti-tumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis. Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. 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Disease Activity, Physical Function, and Radiographic Progression After Longterm Therapy with Adalimumab Plus Methotrexate: 5-Year Results of PREMIER Patient-reported outcomes as predictors of remission in early rheumatoid arthritis patients treated with tight control treat-to-target approach Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone. Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial A Phase III Study Evaluating Continuation, Tapering, and Withdrawal of Certolizumab Pegol After One Year of Therapy in Patients With Early Rheumatoid Arthritis A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis: results from the OPERA randomised controlled trial Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. Impact of physicians’ adherence to treat-to-target strategy on outcomes in early rheumatoid arthritis in the NEO-RACo trial Intra-articular glucocorticoid injections should not be neglected in the remission targeted treatment of early rheumatoid arthritis: a post hoc analysis from the NEO-RACo trial. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. 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Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis
OBJECTIVE To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis ( RA ) . METHODS MTX-naive patients with RA ( n = 637 ) were r and omized to receive placebo plus MTX ( group 1 ) , golimumab 100 mg plus placebo ( group 2 ) , golimumab 50 mg plus MTX ( group 3 ) , or golimumab 100 mg plus MTX ( group 4 ) . Subcutaneous injections of golimumab or placebo were administered every 4 weeks . The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week . The primary end point , the proportion of patients meeting the American College of Rheumatology 50 % improvement criteria ( achieving an ACR50 response ) at week 24 , required significant differences between groups 3 and 4 combined ( combined group ) versus group 1 and significant differences in a pairwise comparison ( group 3 or group 4 versus group 1 ) . RESULTS An intent-to-treat ( ITT ) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 ( 38.4 % and 29.4 % , respectively ; P=0.053 ) , while a post hoc modified ITT analysis ( excluding 3 untreated patients ) of the ACR50 response showed statistically significant differences between the combined group and group 1 ( 38.5 % versus 29.4 % ; P=0.049 ) and between group 3 ( 40.5 % ; P=0.038 ) but not group 4 ( 36.5 % ; P=0.177 ) and group 1 . Group 2 was noninferior to group 1 for the ACR50 response at week 24 ( 33.1 % ; 95 % confidence interval lower bound -5.2 % ; predefined delta value for noninferiority -10 % ) . The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters , including response/remission according to the Disease Activity Score in 28 joints . Serious adverse events occurred in 7 % , 3 % , 6 % , and 6 % of patients in groups 1 , 2 , 3 , and 4 , respectively . CONCLUSION Although the primary end point was not met , the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than , and the efficacy of golimumab alone is similar to , the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients , with no unexpected safety concerns Objective To compare the value that rheumatologists across Europe attach to patients ' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis . Methods In a discrete choice experiment , European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity . Treatments differed in five attributes : efficacy ( improvement and achieved state on disease activity ) , safety ( probability of serious adverse events ) , patient 's preference ( level of agreement ) , medication costs and cost-effectiveness ( incremental cost-effectiveness ratio ( ICER ) ) . A Bayesian efficient design defined 14 choice sets , and a r and om parameter logit model was used to estimate relative preferences for rheumatologists across countries . Cluster analyses and latent class models were applied to underst and preference patterns across countries and among individual rheumatologists . Results Responses of 559 rheumatologists from 12 European countries were included in the analysis ( 49 % females , mean age 48 years ) . In all countries , efficacy dominated treatment decisions followed by economic considerations and patients ’ preferences . Across countries , rheumatologists avoided selecting a treatment that patients disliked . Latent class models revealed four respondent profiles : one traded off all attributes except safety , and the remaining three classes disregarded ICER . Among individual rheumatologists , 57 % disregarded ICER and these were more likely from Italy , Romania , Portugal or France , whereas 43 % disregarded uncommon/rare side effects and were more likely from Belgium , Germany , Hungary , the Netherl and s , Norway , Spain , Sweden or UK . Conclusions Overall , European rheumatologists are willing to trade between treatment efficacy , patients ' treatment preferences and economic considerations . However , the degree of trade-off differs between countries and among individuals Objectives To evaluate the efficacy and safety of adalimumab+methotrexate ( MTX ) in Japanese patients with early rheumatoid arthritis ( RA ) who had not previously received MTX or biologics . Methods This r and omised , double-blind , placebo-controlled , multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA ( ≤2-year duration ) . The primary endpoint was inhibition of radiographic progression ( change ( Δ ) from baseline in modified total Sharp score ( mTSS ) ) at week 26 . Results A total of 171 patients received  adalimumab+MTX ( mean dose , 6.2±0.8 mg/week ) and 163 patients  received MTX alone ( mean dose , 6.6±0.6 mg/week , p<0.001 ) . The mean RA duration was 0.3 years and 315 ( 94.3 % ) had high disease activity ( DAS28>5.1 ) . Adalimumab+MTX  significantly inhibited radiographic progression at week 26 versus MTX alone ( ΔmTSS , 1.5±6.1 vs 2.4±3.2 , respectively ; p<0.001 ) . Significantly more patients in the adalimumab+MTX group ( 62.0 % ) did not show radiographic progression ( ΔmTSS≤0.5 ) versus the MTX alone group ( 35.4 % ; p<0.001 ) . Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission , using various definitions , at 26 weeks versus MTX alone . Combination therapy was well tolerated , and no new safety signals were observed . Conclusions Adalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity Objective Early treatment of patients with rheumatoid arthritis ( RA ) with combination treatment starting with methotrexate , sulfasalazine , hydroxychloroquine and prednisolone ( FIN-RACo strategy ) is superior to monotherapy . A study was undertaken to determine whether infliximab ( INFL ) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome . Methods 99 patients with early untreated active RA were enrolled in an investigator-initiated , r and omised , double-blind , multicentre , parallel-group trial . Primary outcomes were remission and radiological changes at 2 years . All patients started with FIN-RACo . In addition , they were r and omised to receive INFL or placebo ( Pla ) from weeks 4 to 26 . Results At 24 months , 66 % and 53 % , respectively , of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology ( ACR ) criteria ( p=0.19 ) , 26 % and 10 % were in sustained modified ACR remission ( p=0.042 ) and 82 % in both groups were in remission by 28-joint disease activity score ( not significant ) . Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4 , respectively ( p=0.0058 ) . Conclusions Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen . Adding INFL for the first 6 months delays radiological progression Objective To compare the efficacy of etanercept ( ETN ) and methotrexate ( MTX ) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis . Methods In a 78-week multicentre r and omised placebo-controlled superiority trial , 110 DMARD-naïve patients with early clinical synovitis ( ≥1 tender and swollen joint , and within 3 months of diagnosis ) and either rheumatoid factor , anticitrullinated protein antibodies or shared epitope positive were r and omised 1:1 to receive MTX+ETN or MTX+placebo ( PBO ) for 52 weeks . Injections ( ETN or PBO ) were stopped in all patients at week 52 . In those with no tender or swollen joints ( NTSJ ) for > 26 weeks , injections were stopped early . If patients had NTSJ > 12 weeks after stopping the injections , MTX was weaned . The primary endpoint was NTSJ at week 52 . Results No statistically significant difference was seen for the primary endpoint ( NTSJ at week 52 ( 32.5 % vs 28.1 % [ adjusted OR 1.32 ( 0.56 to 3.09 ) , p=0.522 ] ) in the MTX+ETN and MTX+PBO groups , respectively ) . The secondary endpoints did not differ between groups at week 52 or 78 . Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 ( 38.5 % vs 9.2 % , adjusted OR 8.87 ( 2.53 to 31.17 ) , p=0.001 ) and week 12 ( 65.1 % vs 43.8 % , adjusted OR 2.49 ( 1.12 to 5.54 ) , p=0.026 ) . Conclusions In this group of patients with early inflammatory arthritis , almost a third had no tender , swollen joints after 1 year . MTX+ETN was not superior to MTX monotherapy in achieving this outcome . Clinical responses , however , including DAS28-CRP<2.6 , were achieved earlier with MTX+ETN combination therapy . Trial registration number The EMPIRE trial is registered on the following trial registries : Eudract-2005 - 005467 - 29 ; IS RCT N 55428162 ( http://www.controlled-trials.com/IS RCT N55428162/EMPIRE ) . The full trial protocol can be obtained from the corresponding author HighlightsEarly rheumatoid arthritis patients have increased levels of soluble CD83 in plasma . The release of soluble CD83 is independent of TNF‐&agr;.In rheumatoid arthritis sCD83 levels are higher in synovial fluid than in plasma . The level of soluble CD83 in plasma does not correlate with disease activity . CD83 is mainly expressed intracellularly in a variety of different cell types . Abstract Rheumatoid arthritis ( RA ) is an autoimmune disease which may lead to severe disabilities due to structural joint damage and extraarticular manifestations The dendritic cell marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with autoimmune diseases . In RA the levels of soluble CD83 ( sCD83 ) are elevated in synovial fluid , however little is known about CD83 expression and regulation in RA . Therefore , we studied how CD83 is expressed in RA and further evaluated the effect of anti‐TNF‐&agr ; therapy hereon . Early RA patients were r and omized to conventional disease modifying anti‐rheumatic drugs with or without additional anti‐TNF‐&agr ; therapy .  Rheumatoid arthritis patients had increased levels of sCD83 in plasma compared with healthy volunteers . The increase in sCD83 plasma levels were unaffected by anti‐TNF‐&agr ; therapy . In chronic RA patients the levels of sCD83 were higher in synovial fluid than in plasma , and only a limited amount of membrane bound CD83 expression was detected on the surface of cells from peripheral blood and synovial fluid . Finally , confocal microscopy of RA synovial membranes revealed that CD83 was mainly localized intracellularly in a group of cells with diverse morphology including both antigen‐presenting cells and non‐antigen‐presenting cells . Our findings demonstrate that early‐stage RA patients have elevated levels of sCD83 in plasma and that anti‐TNF‐&agr ; treatment has no effect on the sCD83 plasma level . This suggest that in RA patients sCD83 regulation is beyond control of BACKGROUND Tumor necrosis factor ( TNF ) is an important mediator of cachexia , and its blockade prevents catabolism in animal models . However , little evidence shows that anti-TNF therapy is effective in treating cachexia in humans . OBJECTIVE The main aim of this study was to investigate the effect of etanercept , a synthetic soluble TNF receptor , on body composition in patients with early rheumatoid arthritis ( RA ) . DESIGN Twenty-six patients were r and omly assigned to 24 wk of treatment with  etanercept or methotrexate ; the latter is the first-line therapy for RA . Body composition , physical function , disease activity , systemic inflammation , and the circulating insulin-like growth factor ( IGF ) system were measured at baseline ( week 0 ) and at follow-up ( weeks 12 and 24 ) . Twelve patients in each treatment group ( 9 F , 3 M ) completed the study . RESULTS Overall , no important changes in body composition were observed , despite a transient increase in IGF-I at week 12 ( P < 0.01 ) . However , the secondary analysis of those patients ( 6/treatment group ) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained : 44 % of weight gained in the etanercept group was fat-free mass , as compared with only 14 % in the methotrexate group ( P = 0.04 ) . Etanercept and methotrexate were equally effective in controlling the disease and improving physical function . CONCLUSIONS Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo . However , TNF blockade seems to normalize the anabolic response to overfeeding and , if these findings are confirmed , may be useful in conditions characterized by anorexia and weight loss Abstract Rheumatoid arthritis ( RA ) is characterized by chronic joint inflammation and infiltration by activated macrophages . TNFα is a central mediator in this process . The mannose receptor , CD206 , is a scavenger receptor expressed by M2A-macrophages and dendritic cells . It is involved in collagen internalization and degradation . The soluble form has been suggested as a biomarker of M2A-macrophage activation . The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment .  Plasma levels of sCD206 were measured by ELISA in sample s from 155 early RA patients with an average symptom duration of 3 months . Patients were r and omized to 12 months ’ methotrexate and placebo ( PLA ) or methotrexate and adalimumab ( ADA ) treatment  , followed by open-label treatment with disease-modifying anti-rheumatic drugs ( DMARD ) and if needed , ADA .  Disease activity was assessed at baseline and after 3 , 6 , 12 and 24 months . Baseline plasma level of sCD206 in treatment naïve RA patients was 0.33 mg/L ( CI : 0.33–0.38 mg/L ) corresponding to the upper part of the reference interval for healthy controls ( 0.10–0.43 mg/L ) . In the PLA group , sCD206 levels decreased after 3 months , but did not differ from baseline after 6 months . In the ADA group , however , levels remained lower than baseline throughout the treatment period . In conclusion , initially , plasma sCD206  in early RA patients decreased in accordance with disease activity and initiation of DMARD treatment . Treatment with anti-TNFα preserved this decrease throughout the study period Objective To investigate the long-term effects of induction therapy with adalimumab ( ADA ) plus methotrexate ( MTX ) in comparison with placebo ( PBO ) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis ( RA ) . Methods Patients with active early RA ( disease duration of ≤12 months ) were r and omly assigned to receive 40 mg ADA subcutaneously every other week ( eow ) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks . Thereafter , all patients received MTX monotherapy up to week 48 . The primary outcome was the Disease Activity Score 28 ( DAS28 ) at week 48 . Secondary outcomes included proportions of patients in remission ( DAS28<2.6 ) , ACR responses , Health Assessment Question naire ( HAQ ) score and radiographic progression . Results 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX . At baseline , DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups . At week 24 , treatment with ADA/MTX compared with PBO/MTX result ed in a greater reduction in DAS28 ( 3.0±1.2 vs 3.6±1.4 ; p=0.009 ) and other secondary outcomes such as DAS28 remission rate ( 47.9 % vs 29.5 % ; p=0.021 ) and HAQ ( 0.49±0.6 vs 0.72±0.6 ; p=0.0014 ) . At week 48 , the difference in clinical outcomes between groups was not statistically significant ( DAS28 : 3.2±1.4 vs 3.4±1.6 ; p=0.41 ) . Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX ( Sharp/van der Heijde score : ADA/MTX 2.6 vs PBO/MTX 6.4 ; p=0.03 , Ratingen score : 1.7 vs 4.2 ; p=0.01 ) . Conclusions A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48 , even after discontinuation of ADA treatment at week 24 . This sustained effect was not found at the primary endpoint ( DAS28 reduction ) 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 Objectives To investigate the clinical impact of 1-year certolizumab pegol ( CZP ) therapy added to the first year of 2-year methotrexate ( MTX ) therapy , compared with 2-year therapy with MTX alone . Methods  MTX-naïve patients with early rheumatoid arthritis ( RA ) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA ( C-OPERA ) , a multicentre , r and omised , controlled study , which consisted of a 52-week double-blind ( DB ) period and subsequent 52-week post treatment ( PT ) period . Patients were r and omised to optimised MTX+CZP ( n=159 ) or optimised MTX+placebo ( PBO ; n=157 ) . Following the DB period , patients entered the PT period , receiving MTX alone ( CZP+MTX→MTX ; n=108 , PBO+MTX→MTX ; n=71 ) . Patients who flared could receive rescue treatment with open-label CZP . Results 34 CZP+MTX→MTX patients and 14 PBO+MTX→MTX patients discontinued during the PT period . From week 52 through week 104 , significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO+MTX ( week 104 : 84.2 % vs 67.5 % ( p<0.001 ) ) . Remission rates decreased after CZP discontinuation ; however , higher rates were maintained through week 104 in CZP+MTX→MTX versus PBO+MTX→MTX ( 41.5 % vs 29.3 % ( p=0.026 ) , 34.6 % vs 24.2 % ( p=0.049 ) and 41.5 % vs 33.1 % ( p=0.132 ) at week 104 in SDAI , Boolean and DAS28(erythrocyte sedimentation rate ) remission . CZP retreated patients due to flare ( n=28 ) showed rapid clinical improvement . The incidence of overall adverse events was similar between groups . Conclusions  In MTX-naïve patients with early RA with poor prognostic factors , an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years , even after stopping CZP . Trial registration number NCT01451203 Objectives To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate ( MTX ) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe , active , progressive rheumatoid arthritis ( RA ) , with poor prognostic factors over 52 weeks . Methods DMARD-naïve patients with ≤1 year of active RA were r and omised ( 3:1 ) in a double-blind manner to CZP ( 400 mg Weeks 0 , 2 , 4 , then 200 mg Q2W to Week 52)+MTX or PBO+MTX ( the mean optimised-MTX dose=21 and 22 mg/week , respectively ) . Sustained remission ( sREM ) and sustained low disease activity ( sLDA ; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2 , respectively , at both Weeks 40 and 52 ) were the primary and secondary endpoints . Results Patients were r and omised to CZP+MTX ( n=660 ) and PBO+MTX ( n=219 ) . At Week 52 , significantly more patients assigned to CZP+MTX compared with PBO+MTX  achieved sREM ( 28.9 % vs 15.0 % , p<0.001 ) and sLDA ( 43.8 % vs 28.6 % , p<0.001 ) . Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX  ( van der Heijde modified total Sharp score ( mTSS ) mean absolute change from baseline ( CFB ) : 0.2 vs 1.8 , p<0.001 , rate of mTSS non-progressors : 70.3 % vs 49.7 % , p<0.001 ; least squares ( LS ) mean CFB in Health Assessment Question naire-Disability Index ( HAQ-DI ) : −1.00 vs −0.82 , p<0.001 ) . Incidence of adverse events ( AEs ) and serious AEs was similar between treatment groups . Infection was the most frequent AE , with higher incidence for CZP+MTX ( 71.8/100 patient-years ( PY ) ) versus PBO+MTX ( 52.7/100 PY ) ; the rate of serious infection was similar between CZP+MTX ( 3.3/100 PY ) and PBO+MTX ( 3.7/100 PY ) . Conclusions CZP+dose-optimised MTX treatment of DMARD-naïve early RA result ed in significantly more patients achieving sREM and sLDA , improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX . Trial registration number NCT01519791 Introduction Clinical synovitis is often associated with damage to bone and cartilage . Previous data have suggested that joint erosions ( JE ) are more prevalent than joint space narrowing ( JSN ) and that the two processes are partly independent of each other . The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE , in the absence of synovitis . Methods The Prospect i ve Multi-Centre R and omised , Double-Blind , Active Comparator-Controlled , Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis ( PREMIER ) enrolled early rheumatoid arthritis ( RA ) patients who were r and omized to one of three treatments : methotrexate ( MTX ) , adalimumab ( ADA ) , or ADA + MTX .  All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessment s from week 26 to 52 were included . Synovitis was assessed every 2–8 weeks by swollen joint counts between weeks 26 and 52 . Radiographs were taken at week 26 and 52 . Two readers , blinded to time and sequence , scored 14 bilateral joints individually for JE and JSN . Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks . Analyses were performed based on treatment arm and were also performed within individual joints . Results JE and swelling were independently and comparably associated with onset of JSN at week 52 . Assessment by individual joints indicated that existing JE , independent of swelling , was significantly associated with JSN onset in higher proportions of metatarsophalangeal ( MTP ; 7/10 ) than proximal interphalangeal ( PIP ; 1/8 ) or metacarpophalangeal ( MCP ; 1/10 ) joints . Treatment with ADA + MTX  prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage . Conclusions Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint . Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs . Trial registration Clinical trials.gov NCT00195663 . Registered 13 September 2005 Adverse events ( AEs ) are common during disease-modifying antirheumatic drug ( DMARD ) treatment , but their influence on treatment results is unclear . We studied AEs in relation to disease activity in early rheumatoid arthritis ( RA ) . Ninety-nine patients started intensive treatment with three conventional synthetic DMARDs ( csDMARDs ) and oral prednisolone  , and were r and omized to a 6-month induction treatment with infliximab or placebo .  All AEs during the first 12 months of treatment were recorded . We scored each AE based on severity ( scale 1–4 ) and defined the burden of AEs as the sum of these scores . Patients were divided into tertiles according to the burden of AEs . As outcomes , we assessed 28-joint disease activity score ( DAS28 ) levels and remission rates at 12 and 24 months . Three hundred thirty-one AEs in 99 patients were reported , and 27 ( 8 % ) were categorized as severe or serious . Mean burden of AEs per patient was 5.4 ± 4.3 . Seventy-nine AEs ( 24 % ) led to temporary ( n = 52 ) or permanent ( n = 27 ) csDMARD discontinuation . Of discontinuations , 1 , 21 , and 57 were detected in the first , second , and third tertiles , respectively . DAS28 remission rates decreased across tertiles at 12 months ( 94 , 94 , and 76 % ; p for linearity 0.029 ) and at 24 months ( 90 , 86 , and 70 % ; p for linearity 0.021 ) . Mean DAS28 levels increased across tertiles at 12 months ( 1.5 ± 1.0 , 1.7 ± 0.9 , and 1.9 ± 1.2 ; p for linearity 0.021 ) and at 24 months ( 1.4 ± 0.8 , 1.6 ± 1.0 , and 1.9 ± 1.1 ; p for linearity 0.007 ) . High burden of AEs is associated with higher disease activity and lower likelihood of remission in early RA Objective To assess the efficacy and safety of adalimumab plus methotrexate ( ADA+MTX ) compared with methotrexate monotherapy in achieving stable low disease activity ( LDA ; disease activity score ( DAS28(CRP ) ) < 3.2 at weeks 22 and 26 ) and clinical , radiographic and functional outcomes in methotrexate-naive patients with early rheumatoid arthritis ( RA ) . Methods 1032 patients with active RA were r and omly assigned 1:1 to ADA+MTX or placebo plus methotrexate ( PBO+MTX ) for 26 weeks . Treatment modifications were to be made in a subsequent study period based on the achievement of DAS28(CRP ) < 3.2 at weeks 22 and 26 . Post-hoc analyses compared patients achieving stable remission using DAS28 and 2010 ACR/EULAR criteria with those achieving LDA but not remission . Results Among patients completing 6 months , 44 % ( 207/466 ) ADA+MTX versus 24 % ( 112/460 ) PBO+MTX patients achieved stable LDA at weeks 22 and 26 ( p<0.001 ) . Combination therapy was statistically superior to methotrexate in obtaining higher ACR20/50/70 responses , more clinical remissions , greater mean reductions in DAS28(CRP ) , no radiographic progression , and normal functional status at week 26 ( p<0.001 for all ) . The only factor predicting stable LDA was disease activity at week 12 . Patients achieving ACR/EULAR remission , particularly in the PBO+MTX group , had some advantage in radiographic outcomes compared with patients who only achieved LDA ( but not remission ) . The overall frequency of adverse events was comparable between groups . There were more serious infections and deaths in the ADA+MTX group , with a possible age effect . Conclusions Treatment with ADA+MTX was significantly superior to methotrexate alone with respect to clinical , radiographic and functional outcomes in patients with early active RA . Before initiating treatment with adalimumab , individual patient evaluation of the benefit/risk ratio should be carefully considered OBJECTIVES To determine the change in established biomarkers of cardiovascular ( CV ) risk , namely , total cholesterol/high-density lipoprotein cholesterol ratio ( TC/HDL-C ) , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) and insulin resistance ( IR ) in patients with early RA treated with two different treat-to-target strategies . METHODS Fasting glucose , lipids , insulin and NT-proBNP were measured at baseline , weeks 26 and 78 in 79 DMARD-naïve RA patients , free of CV disease , as part of a double-blind r and omized controlled trial of MTX with either infliximab ( IFX ) or methylprednisolone as induction therapy . Homeostasis model assessment -estimated IR ( HOMA-IR ) ( glucose*insulin/405 ) was used to measure IR . Multiple imputation was employed , and linear regression analyses were adjusted for baseline values . RESULTS Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78 . Mean TC/HDL-C , HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78 , although change in NT-proBNP was not statistically significant at week 78 . Changes in TC/HDL-C and NT-proBNP were similar between treatment arms , but HOMA-IR values in the IFX + MTX arm were 42 % lower than those treated with MTX + methylprednisolone at week 78 ( P = 0.003 ) ; the difference remained significant after adjustment for baseline BMI , ACPA positivity , smoking status and intramuscular glucocorticoid use ( P = 0.007 ) . CONCLUSION When implementing a treat-to-target approach , treatment of early RA was associated with improvement in TC/HDL-C , HOMA-IR and NT-proBNP , and a greater long-term improvement in HOMA-IR was seen in those treated with IFX . TRIAL REGISTRATION EU Clinical Trials Register , http://www . clinical trialsregister.eu , Eudract-2005 - 005013 - 37 ; ISRTCNregisrty , http://www.is rct n.com , IS RCT N48638981 Objective To determine the most effective treatment strategy among anticitrullinated protein antibodies (ACPA)-negative patients with early rheumatoid arthritis . Methods In the BeSt study , 184 ACPA-negative patients were r and omised to : ( 1 ) sequential monotherapy , ( 2 ) step-up therapy , ( 3 ) initial combination including prednisone , ( 4 ) initial combination including infliximab . Treatment was targeted at the disease activity score ( DAS ) ≤2.4 . Early response and 10-year outcomes were compared between the four strategy -arms in ACPA-negative patients . Results ACPA-negative patients achieved more short-term functional improvement from initial combination therapy than when on monotherapy ( at month 3 , mean Health Assessment Question naire ( HAQ ) 0.71 vs 0.98 , p=0.006 ; at month 6 , 0.59 vs 0.87 , p=0.004 ) . Functional ability over time was comparable between the strategy -arms ( p=0.551 ) with a mean HAQ of 0.6 at year 10 ( p=0.580 for comparison across the strategy -arms ) . 10-year radiographic progression was negligible ( median 0.5 ) and comparable between the 4 strategy -arms ( p=0.082 ) . At year 10 , remission was achieved by 11/40 ( 28 % ) , 9/45 ( 20 % ) , 17/56 ( 30 % ) and 17/43 patients ( 40 % ) in strategy -arms 1–4 , respectively ( p=0.434 ) . Over time , similar remission percentages were achieved in all strategy -arms ( p=0.815 ) . 18 % , 16 % , 20 % and 21 % in strategy -arms 1 to 4 ( p=0.742 ) were in drug-free remission at year 10 , with a median duration of 60 months across the arms . Conclusions Initial combination therapy with methotrexate , sulfasalazine and prednisone , or methotrexate and infliximab , is the most effective treatment strategy for ACPA-negative patients , result ing in earlier functional improvement than when on initial methotrexate monotherapy . After 10 years of targeted treatment , in all strategy -arms favourable clinical outcomes were achieved and radiographic progression was limited . Trial registration number NTR262 , NTR265 Objective . The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity . Methods . Patients completing the 26-week , r and omized , placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label adalimumab + MTX . Patients were assessed for mean change from baseline in the 28-joint DAS with ESR ( DAS28-ESR ) and modified total Sharp score ( mTSS ) , and for the proportions of patients achieving clinical , functional or radiographic remission . Results . Of 333 patients assessed , 278 ( 137 from the initial adalimumab + MTX and 141 from the initial placebo + MTX groups ) completed the 52-week study . Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX . Open-label adalimumab + MTX  slowed radiographic progression through week 52 in both groups , but patients who received adalimumab + MTX throughout the study exhibited less radiographic progression than those who received placebo + MTX during the first 26 weeks ( mean ΔmTSS at week 52 = 2.56 vs 3.30 , P < 0.001 ) . Conclusion . Delayed addition of adalimumab  in Japanese MTX-naive early RA patients did not impact clinical and functional outcomes at week 52 compared with the earlier addition of adalimumab . However , the accrual of significant structural damage during blinded placebo + MTX therapy contributed to the persistence of differences between the treatment strategies , suggesting that Japanese patients at risk for aggressive disease should benefit from the early inclusion of adalimumab + MTX combination therapy . Trial registration . Clinical Trials.gov ( http:// clinical trials.gov/ ) , NCT00870467 Objectives To evaluate efficacy and safety of combination therapy using certolizumab pegol ( CZP ) and methotrexate ( MTX ) as first-line treatment for  MTX-naive , early rheumatoid arthritis ( RA ) with poor prognostic factors , compared with MTX alone . Methods  MTX-naive , early RA patients with ≤12 months persistent disease , high anti-cyclic citrullinated peptide , and either rheumatoid factor positive and /or presence of bone erosions were enrolled in this multicentre , double-blind , r and omised placebo (PBO)-controlled study . Patients were r and omised 1:1 to CZP+MTX or PBO+MTX for 52 weeks . Primary endpoint was inhibition of radiographic progression ( change from baseline in modified Total Sharp Score ( mTSS CFB ) ) at week 52 . Secondary endpoints were mTSS CFB at week 24 , and clinical remission rates at weeks 24 and 52 . Results 316 patients r and omised to CZP+MTX ( n=159 ) or PBO+MTX ( n=157 ) had comparable baseline characteristics reflecting features of early RA ( mean disease duration : 4.0 vs 4.3 months ; Disease Activity Score 28-joint assessment ( DAS28 ) ) ( erythrocyte sedimentation rate ( ESR ) ) : 5.4 vs 5.5 ; mTSS : 5.2 vs 6.0 ) . CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 ( mTSS CFB=0.36 vs 1.58 ; p<0.001 ) and week 24 ( mTSS CFB=0.26 vs 0.86 ; p=0.003 ) . Clinical remission rates ( Simple Disease Activity Index , Boolean and DAS28 ( ESR ) ) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group , at weeks 24 and 52 . Safety results in both groups were similar , with no new safety signals observed with addition of CZP to MTX . Conclusions In  MTX-naive early RA patients with poor prognostic factors  , CZP+MTX  significantly inhibited structural damage and reduced RA signs and symptoms , demonstrating the efficacy of CZP in these patients . Trial registration number ( NCT01451203 ) OBJECTIVES In early and active RA despite MTX , continuous treatment with TNF blockers in combination with MTX is recommended . To compare this strategy with an initial combination of MTX and adalimumab ( ADA ) given for 3 months and then adjusted based on the disease activity status . METHODS Prospect i ve unblinded r and omized multicentre controlled 1-year trial in which 65 patients with early ( < 6 months ) and active [ disease activity score ( DAS28(ESR ) ) > 5.1 ] RA were assigned to Group 1 ( 32 patients ):  MTX ( 0.3 mg/kg/week , maximum of 20 mg/week , without escalating dose regimen ) or to Group 2 ( 33 patients ): initial combination therapy with MTX ( as in Group 1 ) and ADA ( 40 mg eow ) . In both groups , treatment was adjusted every 3 months . The aim was to achieve a low DAS ( DAS28(ESR ) < 3.2 ) . RESULTS From Week 12 until Week 52 , seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy ( P = 0.28 ) . The 1-year area under the curve ( AUC ) of DAS28 was lower in Group 2 owing to an initial better response . The total intake of anti-TNF-alpha and the mean increase in total modified Sharp score was similar in the two groups . CONCLUSIONS Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-alpha treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX Purpose We assessed whether MRI measures of synovitis , osteitis and bone erosion were associated with patient-reported outcomes ( PROs ) in a longitudinal clinical trial setting among patients with rheumatoid arthritis ( RA ) . Methods This longitudinal cohort of 291 patients with RA was derived from the MRI sub study of the GO-BEFORE r and omised controlled trial of golimumab among methotrexate-naïve patients . Correlations between RAMRIS scores ( synovitis , osteitis , bone erosion ) and physical function ( Health Assessment Question naire ( HAQ ) ) , pain and global patient scores were determined at 0 , 12 , 24 and 52 weeks . Correlations between interval changes were also assessed . Multivariable regression models using robust generalised estimating equations evaluated associations over all time-points and their relationship to other clinical disease activity measures . Results Greater synovitis , osteitis and bone erosion scores were positively associated with HAQ at all time-points ( all p<0.05 ) and with pain and patient global scores at 24 and 52 weeks . Over all visits , synovitis was associated with HAQ , pain and patient global scores ( p≤0.03 ) independent of clinical disease activity measures . Improvements in synovitis and bone erosion were also associated with improvements in PROs . Less improvement in synovitis and progression in MRI erosion at 52 weeks were both independently associated with worsening in all PROs at 52 weeks while progression on X-ray was not associated . Similar associations were observed across treatment groups . Conclusions MRI measures of inflammation and structural damage correlate independently with physical function , pain and patient global assessment s. These observations support the validity of MRI biomarkers . Trial registration number NCT00264537 ; Post- results OBJECTIVE To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis ( RA ) who received monotherapy with either etanercept or methotrexate ( MTX ) for 2 years and to assess the safety of this therapy . METHODS In the Enbrel ERA ( early rheumatoid arthritis ) trial , 632 patients with early , active RA were r and omized to receive either twice-weekly subcutaneous etanercept ( 10 mg or 25 mg ) or weekly oral MTX ( mean dosage 19 mg per week ) for at least 1 year in a double-blind manner . Following the blinded phase of the trial , 512 patients continued to receive the therapy to which they had been r and omized for up to 1 additional year , in an open-label manner . Radiograph readers remained blinded to treatment group assignment and the chronologic order of images . RESULTS At 24 months , more 25-mg etanercept patients than MTX patients met American College of Rheumatology 20 % improvement criteria ( 72 % and 59 % , respectively ; P = 0.005 ) , and more had no increase in total score and erosion scores on the Sharp scale ( P = 0.017 and P = 0.012 , respectively ) . The mean changes in total Sharp score and erosion score in the 25-mg etanercept group ( 1.3 and 0.66 units , respectively ) were significantly lower than those in the MTX group ( 3.2 and 1.86 units , respectively ; P = 0.001 ) . Significantly more patients in the 25-mg etanercept group ( 55 % ) than in the MTX group ( 37 % ) had at least 0.5 units of improvement in the Health Assessment Question naire disability index ( P < 0.001 ) . Fewer patients in the etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events . CONCLUSION Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity , arresting structural damage , and decreasing disability over 2 years in patients with early , aggressive RA Objectives In disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis ( RA ) , to compare the efficacy of methotrexate ( MTX ) and infliximab ( IFX ) with MTX and intravenous corticosteroid for remission induction . Methods In a 78-week multicentre r and omised controlled trial , double-blinded to week 26 , 112 treatment-naive RA patients ( 1987 American College of Rheumatology classification criteria ) with disease activity score 44 (DAS44)>2.4 were r and omised to  MTX + IFX or MTX + single dose intravenous methylprednisolone 250 mg . A treat-to-target approach was used with treatment escalation if DAS44>2.4 . In the IFX group , IFX was discontinued for sustained remission ( DAS44<1.6 for 6 months ) . The primary outcome was change in modified total Sharp-van der Heijde score ( mTSS ) at week 50 . Results The mean changes in mTSS score at week 50 in the IFX and intravenous steroid groups were 1.20 units and 2.81 units , respectively ( adjusted difference ( 95 % CI ) −1.45 ( −3.35 to 0.45 ) ; p=0.132 ) . Radiographic non-progression ( mTSS<2.0 ) occurred in 81 % vs 71 % ( OR 1.77 ( 0.56 to 5.61 ) ; p=0.328 ) . DAS44 remission was achieved at week 50 in 49 % and 36 % ( OR 2.13 ( 0.91 to 5.00 ) ; p=0.082 ) , and at week 78 in 48 % and 50 % ( OR 1.12 ( 0.47 to 2.68 ) ; p=0.792 ) . Exploratory analyses suggested higher DAS28 remission at week 6 and less ultrasound synovitis at week 50 in the IFX group . Of the IFX group , 25 % ( 14/55 ) achieved sustained remission and stopped IFX . No substantive differences in adverse events were seen . Conclusions In DMARD-naive early RA patients , initial therapy with MTX+high-dose intravenous steroid result ed in good disease control with little structural damage . MTX+IFX was not statistically superior to MTX+intravenous steroid when combined with a treat-to-target approach OBJECTIVE To compare work disability and job loss in early rheumatoid arthritis ( RA ) patients receiving adalimumab plus methotrexate ( adalimumab + MTX ) versus MTX alone .  METHODS In this multicenter , r and omized , controlled trial , patients with RA for < 2 years who had never taken MTX and who self-reported work impairment were r and omized to  adalimumab + MTX or placebo + MTX for 56 weeks . Primary outcome was job loss of any cause and /or imminent job loss at or after week 16 . Secondary outcomes included disease activity , function ( Health Assessment Question naire [ HAQ ] score ) , and RA quality of life ( RAQoL ) question naire score . Work was evaluated with work diaries and the RA Work Instability Scale . RESULTS Although job loss during the 56-week study was significantly lower with adalimumab + MTX ( 14 of 75 patients ) compared with MTX alone ( 29 of 73 patients ; P=0.005 ) , the primary end point was not met ( 12 of 75 versus 20 of 73 patients ; P=0.092 ) , likely owing to early drop out in the MTX group . There were significant improvements in American College of Rheumatology 20 % response criteria , 28-joint Disease Activity Score , DeltaHAQ , DeltaRAQoL , and working time lost in the adalimumab + MTX group . Twenty-four serious adverse events were reported in 17 participants , with no differences between groups . CONCLUSION Adalimumab + MTX reduced job loss and improved productivity in early RA when compared with MTX alone , which supports the early use of anti-tumor necrosis factor therapy and suggests its cost efficacy At least 30 % of patients with rheumatoid arthritis ( RA ) do not respond to biologic agents , which emphasizes the need of predictive biomarkers . We aim ed to identify microRNAs ( miRNAs ) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA ( OPERA ) Study , an investigator-initiated , prospect i ve , double-blind placebo-controlled study . Patients were r and omized to adalimumab 40 mg ( n=89 ) or placebo – adalimumab ( n=91 ) subcutaneously in combination with methotrexate .  Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA , A Card v2.0 ( Applied Biosystems ) . Associations between miRNAs and treatment response were tested using interaction analyses . MiRNAs with a P-value < 0.05 using three different normalizations were included in a multivariate model . After backwards elimination , the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response . Future studies to assess the utility of these miRNAs as predictive biomarkers are needed 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 Objective YKL-40 , a chitinase-like glycoprotein associated with inflammation and tissue remodeling , is produced by joint tissues and recognized as a c and i date auto-antigen in rheumatoid arthritis ( RA ) . In the present study , we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aim ing for early remission . Methods Ninety-nine patients with early DMARD-naïve RA participated in the NEO-RACo study . For the first four weeks , the patients were treated with the combination of sulphasalazine , methotrexate , hydroxychloroquine and low dose prednisolone ( FIN-RACo DMARD combination ) , and subsequently r and omized to receive placebo or infliximab added on the treatment for further 22 weeks . Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay . Results At the baseline , plasma YKL-40 concentration was 57 ± 37 ( mean ± SD ) ng/ml . YKL-40 was significantly associated with the disease activity score , interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks ’ treatment . The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment , and there was no further reduction when the tumour necrosis factor-α antagonist infliximab was added on the combination treatment . Conclusions High YKL-40 levels were found to be associated with disease activity in early DMARD-naïve RA and during intensive treat-to-target therapy . The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission Objective To compare clinical and radiological outcomes of four dynamic treatment strategies in recent-onset rheumatoid arthritis ( RA ) after 5 years follow-up . Methods 508 patients with recent-onset RA were r and omly assigned into four treatment strategies : sequential monotherapy ; step-up combination therapy ; initial combination with prednisone ; initial combination with infliximab . Treatment adjustments were made based on 3-monthly disease activity score ( DAS ) measurements ( if DAS > 2.4 next treatment step ; if DAS ≤2.4 during ≥6 months taper to maintenance dose ; if DAS < 1.6 during ≥6 months stop antirheumatic treatment ) . Primary and secondary outcomes were functional ability , joint damage progression , health-related quality of life and ( drug-free ) remission percentages . Results After 5 years , 48 % of patients were in clinical remission ( DAS < 1.6 ) and 14 % in drug-free remission , irrespective of initial treatment . After an earlier improvement in functional ability and quality of life with initial combination therapy , from 1 year onwards clinical outcomes were comparable across the groups and stable during 5 years . The initial combination groups showed less joint damage in year 1 . In years 2–5 annual progression was comparable across the groups . After 5 years , initial combination therapy result ed in significantly less joint damage progression , reflecting the earlier clinical response . Conclusion Irrespective of initial treatment , an impressive improvement in clinical and radiological outcomes of RA patients can be achieved with dynamic treatment aim ed at reducing disease activity , leading to 48 % remission , 14 % drug-free remission and sustained functional improvement . Starting with combination therapy result ed in earlier clinical improvement and less joint damage without more toxicity OBJECTIVES Rheumatoid arthritis ( RA ) is a chronic autoimmune disease where TNF-α is a central mediator of inflammation , and is cleaved from the cell surface by TACE/ADAM17 . This metalloproteinase is also responsible for the release of soluble ( s ) CD163 . Soluble CD163 reflects macrophage activation . In RA , sCD163 has been suggested as a marker of disease activity and progression . Our aim is to investigate sCD163 levels in early RA patients . METHODS Soluble CD163 was measured by ELISA from 150 RA plasma sample s from the OPERA trial . Averaged  disease duration was three months , prior to r and omisation with methotrexate ( MTX ) and adalimumab ( DMARD+ADA ) or MTX and placebo ( DMARD+PLA ) . Soluble CD163 levels were evaluated in relation to clinical disease parameters . RESULTS Plasma sCD163 at baseline was 2.39 mg/l ( 1.74 mg/l-3.18 mg/l ) , mean ( 95 % CI ) , vs healthy controls : 1.63 mg/l ( 1.54 mg/l - 1.73 mg/l ) , ( p<0.001 ) . After three months of treatment sCD163 levels decreased significantly ( average 23.5 % ) in both treatment groups . Significant incremental sCD163 levels followed withdrawal of ADA after 12 months of treatment . Baseline sCD163 correlated with CRP and all investigated disease activity markers ( ρ=0.16 - 0.28 , p<0.05 ) . In the DMARD+PLA group baseline sCD163 also correlated with CRP during the follow-up period . CONCLUSIONS Soluble CD163 correlated with disease activity markers in early RA before treatment . Plasma sCD163 may add to currently available disease measures by specifically reflecting changes in macrophage activity as evidence d by increasing levels following anti-TNF withdrawal , despite maintenance of a stable clinical condition achieved by conventional remedies . It remains to be determined whether sCD163 is an early predictor of disease flare Objective . To evaluate the efficacy and safety of initial combination treatment with adalimumab ( ADA ) and methotrexate ( MTX ) versus monotherapy with ADA or MTX during an open-label extension of PREMIER . Methods . Patients with early rheumatoid arthritis ( RA ) received blinded ADA plus MTX , ADA alone , or MTX alone for 2 years in PREMIER . At Year 2 , patients could enroll in an open-label extension and receive ADA monotherapy ; MTX could be added at the investigator ’s discretion . Longterm efficacy results are presented as observed data . Results . In the open-label period , 497 of the original 799 r and omized patients had ≥ 1 dose of ADA  ( by original r and omization : ADA plus MTX , n = 183 ; ADA , n = 159 ; MTX , n = 155 ) . In the completers cohort [ patients with available Year-5 ACR responses and modified total Sharp scores ( mTSS ) ] , the Year-5 mean change from baseline in mTSS for the ADA+MTX arm ( n = 124 ) was 2.9 , compared with 8.7 and 9.7 in the ADA ( n = 115 ) and MTX ( n = 115 ) arms . Comprehensive disease remission , defined as the combination of DAS28 remission , normal function ( Health Assessment Question naire ≤ 0.5 ) , and radiographic nonprogression ( ΔmTSS ≤ 0.5 ) , was achieved by more patients in the initial ADA+MTX arm ( 35 % ) than in the ADA ( 13 % ) or MTX ( 14 % ) arms . Conclusion . Initial combination treatment with ADA plus MTX , followed by open-label ADA , led to better longterm clinical , functional , and radiographic outcomes than either initial ADA or MTX monotherapy during 5 years of treatment Identifying prognostic factors for remission in early rheumatoid arthritis ( ERA ) patients is of key clinical importance . We studied patient-reported outcomes ( PROs ) as predictors of remission in a clinical trial . We r and omized 99 untreated ERA patients to receive  remission-targeted  treatment with three disease-modifying antirheumatic drugs and prednisolone for 24 months , and infliximab or placebo for the initial 6 months . At baseline , we measured following PROs : eight Short Form 36 question naire ( SF-36 ) dimensions , patient ’s global assessment [ PGA , visual analogue scale ( VAS ) ] , Health Assessment Question naire ( HAQ ) , and pain VAS . We used multivariable-adjusted regression models to identify PROs that independently predicted modified American College of Rheumatology remission at 2 years . Follow-up data at 2 years were available for 93 patients ( 92 % ) , and 58 patients ( 62 % ) were in remission . At baseline , patients who achieved remission had higher radiological score ( p = 0.04 ) , lower tender joint count ( p = 0.001 ) , lower PGA ( p = 0.005 ) and physician ’s global assessment ( p = 0.019 ) , lower HAQ ( p = 0.016 ) , less morning stiffness ( p = 0.009 ) , and significantly higher scores in seven out of eight SF-36 dimensions compared with patients who did not . In multivariable models that included all PROs , remission was associated with SF-36 dimensions higher vitality ( odds ratio 2.01 ; 95 % confidence interval 1.19–3.39 ) and better emotional role functioning ( odds ratio 1.64 ; 95 % confidence interval 1.01–2.68 ) . PGA , pain VAS , HAQ , and other SF-36 dimensions were not associated with remission . We conclude that self-reported vitality and better emotional role functioning are among the most important PROs for the prediction of remission in ERA BACKGROUND Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis . The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis ( COMET ) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept . METHODS 542 out patients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3 - 24 months were r and omly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate ( same titration ) plus etanercept 50 mg a week . Co primary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints ( DAS28 ) and radiographic non-progression measured with modified total Sharp score . Treatment was allocated with a computerised r and omisation and enrolment system , which masked both participants and carers . Analysis was done by modified intention to treat with last observation carried forward for missing data . This study is registered with Clinical Trials.gov , number NCT00195494 ) . FINDINGS 274 participants were r and omly assigned to receive combined treatment and 268  methotrexate alone . 132 of 265 ( 50 % , 95 % CI 44 - 56 % ) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 ( 28 % , 23 - 33 % ) taking methotrexate alone ( effect difference 22.05 % , 95%CI 13.96 - 30.15 % , p<0.0001 ) . 487 evaluable patients had severe disease ( DAS28>5.1 ) . 196 of 246 ( 80 % , 75 - 85 % ) and 135 of 230 ( 59 % , 53 - 65 % ) , respectively , achieved radiographic non-progression ( 20.98 % , 12.97 - 29.09 % , p<0.0001 ) . Serious adverse events were similar between groups . INTERPRETATION Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate . FUNDING Wyeth Research OBJECTIVE To compare the effects of methotrexate ( MTX ) , alone or in combination with intravenous ( IV ) methylprednisolone ( MP ) or infliximab , on magnetic resonance imaging (MRI)-detected synovitis , bone edema , and erosive changes in patients with early rheumatoid arthritis ( RA ) . METHODS Forty-four patients with early RA were r and omized to receive MTX alone ( MTX group ) , MTX plus IV MP ( IV MP group ) , or MTX plus infliximab ( infliximab group ) , infused on day 0 and weeks 2 , 6 , 14 , 22 , 30 , 38 , and 46 . Gadolinium-enhanced MRI scans of the metacarpophalangeal joints , wrists , and metatarsophalangeal joints were performed at baseline , week 18 , and week 52 . RESULTS Scores for MRI-detected synovitis and bone edema improved over time in the 3 groups , with significantly lower synovitis scores in the infliximab group compared with the MTX group and significantly lower bone edema scores in the infliximab group compared with the MTX and the IV MP groups . Scores for MRI-detected erosion significantly increased over time in all groups . There were no differences in erosion scores between the MTX group and the other groups . It is of note that patients treated with IV MP showed more significant progression in MRI-detected erosions compared with patients treated with infliximab . At week 22 , response rates according to the American College of Rheumatology 20 % improvement criteria ( ACR20 ) , the ACR50 , and the ACR70 were significantly higher in both the IV MP group and the infliximab group compared with the MTX group . At week 52 , remission was achieved in 40 % of patients in the MTX group and in 70 % of patients in the IV MP and infliximab groups . Health Assessment Question naire scores improved significantly over time in all groups , with patients receiving IV MP experiencing significantly more improvement compared with patients treated with MTX alone . No severe side effects were observed , except 1 case of MTX-related pneumonitis . CONCLUSION The combination of MTX and infliximab is superior to MTX alone for reducing MRI-detected signs of synovitis and bone edema in patients with early RA . Progression of MRI-detected erosion was greater in patients treated with MTX plus IV MP compared with that in patients who received MTX plus infliximab Objective To study whether adding initial infliximab to remission-targeted initial combination-DMARD treatment improves the long-term outcomes in patients with early rheumatoid arthritis ( RA ) . Methods Ninety-nine patients with early , DMARD-naïve RA were treated with a triple combination of DMARDs , starting with methotrexate ( max 25 mg/week ) , sulfasalazine ( max 2 g/day ) , hydroxychloroquine ( 35 mg/kg/week ) , and with prednisolone ( 7.5 mg/day ) , and r and omised to double blindly receive either infliximab ( 3 mg/kg ; FIN-RACo+INFL ) or placebo ( FIN-RACo+PLA ) infusions during the first 6 months . After 2 years the treatment strategies became unrestricted , but the treatment goal was strict ACR remission . At 5 years the clinical and radiographic outcomes were assessed . Results Ninety-one patients ( 92 % ) were followed up to 5 years , 45 in the FIN-RACo+INFL and 46 in the FIN-RACo+PLA groups . At 5 years , the respective proportions of patients in strict ACR and in disease activity score 28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 60 % ( 95 % CI 44 % to 74 % ) and 61 % ( 95 % CI 45 % to 75 % ) ( p=0.87 ) , and 84 % ( 95 % CI 71 % to 94 % ) and 89 % ( 95 % CI 76 % to 96 % ) ( p=0.51 ) . The corresponding mean ( SD ) total Sharp/van der Heijde scores at 5 years were 4.3 ( 7.6 ) , and 5.3 ( 7.3 ) , while the respective mean Sharp/van der Heijde scores changes from baseline to 5 years were 1.6 ( 95 % CI 0.0 to 3.4 ) and 3.7 ( 95 % CI 2.2 to 5.8 ) ( p=0.13 ) . Conclusions In early RA , targeted treatment with a combination of traditional DMARDs and prednisolone induces remission and minimises radiographic progression in most patients up to 5 years ; adding initial infliximab for 6 months does not improve these outcomes In disease‐modifying antirheumatic drug – naive patients with early rheumatoid arthritis ( RA ) who had achieved sustained low disease activity ( a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate of ≤3.2 at both week 40 and week 52 ) after 1 year of treatment with certolizumab pegol ( CZP ) at a st and ard dose ( 200 mg every 2 weeks plus optimized methotrexate [ MTX ] ) , we evaluated whether continuation of CZP treatment at a st and ard dose or at a reduced frequency ( 200 mg every 4 weeks plus MTX ) was superior to stopping CZP ( placebo plus MTX ) in maintaining low disease activity for 1 additional year Objectives To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis ( ERA ) , and whether adalimumab provides an additional effect . Methods In a double-blind , placebo-controlled trial , 85 disease-modifying antirheumatic drug-naïve patients with ERA were r and omised to receive methotrexate , intra-articular glucocorticosteroid injections and placebo/adalimumab ( 43/42 ) .  Contrast-enhanced MRI of the right h and was performed at months 0 , 6 and 12 . Synovitis , osteitis , tenosynovitis , MRI bone erosion and joint space narrowing ( JSN ) were scored with vali date d methods . Dynamic contrast-enhanced MRI ( DCE-MRI ) was carried out in 14 patients .  Results Synovitis , osteitis and tenosynovitis scores decreased highly significantly ( p<0.0001 ) during the 12-months ’ follow-up , with mean change scores of −3.7 ( median −3.0 ) , −2.2 ( −1 ) and −5.3 ( −4.0 ) , respectively . No overall change in MRI bone erosion and JSN scores was seen , with change scores of 0.1 ( 0 ) and 0.2 ( 0 ) . The tenosynovitis score at month 6 was significantly lower in the adalimumab group , 1.3 ( 0 ) , than in the placebo group , 3.9 ( 2 ) , Mann – Whitney : p<0.035 . Furthermore , the osteitis score decreased significantly during the 12-months ’ follow-up in the adalimumab group , but not in the placebo group , Wilcoxon : p=0.001–0.002 and p=0.062–0.146 . DCE-MRI parameters correlated closely with conventional MRI inflammatory parameters . Clinical measures decreased highly significantly during follow-up . Conclusions A treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid in patients with ERA effectively decreased synovitis , osteitis and tenosynovitis and halted structural damage progression as judged by MRI . The findings suggest that addition of adalimumab is associated with further suppression of osteitis and tenosynovitis BACKGROUND Biological agents offer good control of rheumatoid arthritis , but the long-term benefits of achieving low disease activity with a biological agent plus methotrexate or methotrexate alone are unclear . The OPTIMA trial assessed different treatment adjustment strategies in patients with early rheumatoid arthritis attaining ( or not ) stable low disease activity with adalimumab plus methotrexate or methotrexate monotherapy . METHODS This trial was done at 161 sites worldwide . Patients with early ( < 1 year duration ) rheumatoid arthritis naive to methotrexate  were r and omly allocated ( by interactive voice response system , in a 1:1 ratio , block size four ) to adalimumab ( 40 mg every other week ) plus methotrexate ( initiated at 7·5 mg/week , increased by 2·5 mg every 1 - 2 weeks to a maximum weekly dose of 20 mg by week 8) or placebo plus methotrexate for 26 weeks ( period 1 ) . Patients in the  adalimumab plus methotrexate  group who completed period 1 and achieved the stable low disease activity target ( 28-joint disease activity score with C-reactive protein [DAS28]<3·2 at weeks 22 and 26 ) were r and omised to adalimumab-continuation or adalimumab-withdrawal for an additional 52 weeks ( period 2 ) . Patients achieving the target with initial methotrexate continued methotrexate-monotherapy . Inadequate responders were offered adalimumab plus methotrexate . All patients and investigators were masked to treatment allocation in period 1 . During period 2 , treatment reallocation of patients who achieved the target was masked to patients and investigators ; patients who did not achieve the target remained masked to original r and omisation , but were aware of the subsequent assignment . The primary endpoint was a composite measure of DAS28 of less than 3·2 at week 78 and radiographic non-progression from baseline to week 78 , compared between adalimumab-continuation and methotrexate-monotherapy  . Adverse events were monitored throughout period 2 . This trial is registered with Clinical Trials.gov , number NCT00420927 . FINDINGS The study was done between Dec 28 , 2006 , and Aug 3 , 2010 . 1636 patients were assessed and 1032 were r and omised in period 1 ( 515 to adalimumab plus methotrexate ; 517 to placebo plus methotrexate ) . 466 patients in the adalimumab plus methotrexate group completed period 1 ; 207 achieved the stable low disease activity target , of whom 105 were rer and omised to adalimumab-continuation . 460 patients in the placebo plus methotrexate group completed period 1 ; 112 achieved the stable low disease activity target and continued methotrexate-monotherapy . 73 of 105 ( 70 % ) patients in the adalimumab-continuation group and 61 of 112 ( 54 % ) patients in the methotrexate-monotherapy group achieved the primary endpoint at week 78 ( mean difference 15 % [ 95 % CI 2 - 28 % ] , p=0·0225 ) . Patients achieving the stable low disease activity target on adalimumab plus methotrexate who withdrew adalimumab mostly maintained their good responses . Overall , 706 of 926 patients in period 2 had an adverse event , of which 82 were deemed serious ; however , distribution of adverse events did not differ between groups . INTERPRETATION Treatment to a stable low disease activity target result ed in improved clinical , functional , and structural outcomes , with both adalimumab-continuation and methotrexate-monotherapy . However , a higher proportion of patients treated with initial adalimumab plus methotrexate achieved the low disease activity target compared with those initially treated with methotrexate alone . Outcomes were much the same whether adalimumab was continued or withdrawn in patients who initially responded to adalimumab plus methotrexate . FUNDING AbbVie OBJECTIVE To evaluate safety , efficacy , and radiographic progression in patients with early rheumatoid arthritis ( RA ) undergoing longterm treatment with etanercept .  METHODS Patients with early RA ( disease duration of 3 years or less ) who had completed a 2-year efficacy study comparing etanercept and methotrexate ( MTX ) were followed in an extension where they received 25 mg etanercept twice weekly . Safety was summarized descriptively and compared with data from the efficacy study . Efficacy and radiographic progression were assessed using American College of Rheumatology response criteria , disease activity scores , and Total Sharp Score ( TSS ) . RESULTS Rates of serious adverse events and serious infections did not increase with longterm exposure to etanercept , and were similar to rates reported for the blinded portion of the efficacy study . Efficacy was sustained in patients who completed 5 years of etanercept treatment at the time of this report ( N = 201 ) , even in those who decreased or discontinued use of MTX or corticosteroids . No radiographic progression ( change in TSS < or = 0 ) was seen in 55 % of patients with 5-year radiographs ; negative change ( TSS < 0 ) was seen in 11 % . CONCLUSION Etanercept treatment in patients with early RA was generally well tolerated for up to 5 years . The results indicate sustained efficacy and decreased rate of radiographic progression . The rate of radiographic progression was low compared with other studies , emphasizing the benefit gained in patients with early aggressive RA who undergo longterm treatment with etanercept Objectives : It is well recognized that medication adherence of rheumatoid arthritis ( RA ) patients is often poor . As less attention has been paid to physicians ’ adherence to targeted treatment , we aim ed to investigate how it affects outcomes in aggressively treated early RA patients . Method : In the new Finnish RA Combination Therapy ( NEO-RACo ) trial , 99 patients with early active RA were treated , targeting remission , with a combination of methotrexate , sulfasalazine , hydroxychloroquine , and low-dose prednisolone for 2 years , and r and omized to receive infliximab or placebo for the initial 6 months . After 2 years , therapy was unrestricted while remission was still targeted . Patients were divided into tertiles by physicians ’ adherence to treat-to-target , which was evaluated with a scoring system during the initial 2 years . After 5 years of follow-up , the between-tertile differences in remission rates , 28-joint Disease Activity Score ( DAS28 ) levels , radiological changes , cumulative days off work , and the use of anti-rheumatic medication were assessed . Results : Follow-up data were available for 93 patients . Physicians ’ good adherence was associated with improved remission rates at 2–4 years and lower DAS28 levels throughout the follow-up . In a multivariable model , physicians ’ adherence was the most important predictor of remission at 3 months and 2 years ( p < 0.001 for both ) . Between 2 and 5 years , biologics were used more often in the tertile of low adherence compared with the other two groups ( p = 0.024 ) . No significant differences were observed in radiological progression and cumulative days off work . Conclusions : Physicians ’ good adherence is associated with improved remission rates and lesser use of biologics in early RA OBJECTIVES To study the effects of neglecting intra-articular glucocorticoid injections ( IAGCIs ) into swollen joints in early rheumatoid arthritis ( RA ) . METHODS Ninety-nine patients with early , DMARD naive RA were treated , aim ing at remission , with methotrexate , sulfasalazine , hydroxychloroquine , low-dose oral prednisolone and , when needed , IAGCIs for 2 years , and r and omised to receive infliximab or placebo from weeks 4 to 26 . During each of the 15 study visits , patients were scored retrospectively 0.2 - 0.4 points ( depending on the number of non-injected joints ) if IAGCIs to all swollen joints were not given . Patients were divided into tertiles by their cumulative scores for neglected injections ( CSNI ) over 24 months . 28-joint disease activity score ( DAS28 ) area under the curve ( AUC ) between 0 - 24 months , remission rates , changes in quality of life , and radiological changes during the follow-up were assessed . Trends across tertiles of CSNI were tested with generalised linear models . RESULTS Higher CSNI was associated with lower strict remission rates ( p=0.005 ) , and lower quality of life ( p=0.004 ) at 24 months , and higher DAS28 AUC ( p<0.001 ) during the follow-up . At 24 months , DAS28 remission rates were 90 % , 93 % and 76 % ( p=0.081 ) , and strict remission rates were 74 % , 77 % and 39 % by tertiles of CSNI . No significant differences were observed in radiological progression ( p=0.089 ) . IAGCIs were well tolerated . CONCLUSIONS Neglecting IAGCIs into swollen joints is associated with lower remission rates , higher disease activity , and lower quality of life . Hence , IAGCIs should be used as an integral part of the targeted treatment of early RA 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 Objectives To study clinical and radiographic outcomes after withdrawing 1 year 's adalimumab induction therapy for early rheumatoid arthritis ( eRA ) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy ( NCT00660647 ) . Methods Disease-modifying antirheumatic drug (DMARD)-naive patients with eRA started methotrexate ( 20 mg/week ) and intra-articular triamcinolone ( 20 mg/ml ) for 2 years . In addition , they were r and omised to receive  placebo adalimumab ( DMARD group , n=91 ) or adalimumab (  40 mg/every other week ) ( DMARD+adalimumab group , n=89 ) during the first year . Sulfasalazine and hydroxychloroquine were added if disease activity persisted after 3 months . During year 2 , synthetic DMARDs continued . Adalimumab was (re)initiated if active disease reoccurred . Clinical response , remission , disability , quality of life and radiographic changes were assessed . Results One year after adalimumab withdrawal , treatment profiles and clinical responses did not differ between groups . In the DMARD/DMARD+adalimumab groups , the median 2-year methotrexate dose was 20/20 mg/week ( p=0.45 ) , triple DMARD therapy had been initiated in 33/27 patients ( p=0.49 ) , adalimumab was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg ( p=0.15 ) . The treatment target ( disease activity score , 4 variables , C-reactive protein ( DAS28CRP ) ≤3.2 or DAS28>3.2 without swollen joints ) was achieved at all visits in ≥85 % of patients in year 2 ; remission rates were DAS28CRP<2.6:69%/66 % ; Clinical Disease Activity Index ≤2.8:55%/57 % ; Simplified Disease Activity Index < 3.3:54%/49 % ; American College of Rheumatology/European League against Rheumatism ( 28 joints):44%/45 % ( p=0.66–1.00 ) . Radiographic progression ( Δtotal Sharp score/year ) was similar 1.31/0.53 ( p=0.12 ) . Erosive progression ( Δerosion score (ES)/year ) was year 1:0.57/0.06 ( p=0.02 ) ; year 2:0.38/0.05 ( p=0.005 ) . Proportion of patients without erosive progression ( ΔES≤0 ) was year 1 : 59%/76 % ( p=0.03 ) ; year 2:64%/79 % ( p=0.04 ) . Conclusions An aggressive triamcinolone and synthetic DMARD treat-to-target strategy in eRA provided excellent 2-year clinical and radiographic disease control independent of adalimumab induction therapy . ES progression was slightly less during and following adalimumab induction therapy . Trial registration number NCT00660647 Objective . Rheumatoid arthritis ( RA ) is associated with significant impairments in health-related quality of life ( HRQOL ) . We evaluated patient-reported outcomes including HRQOL outcomes following adalimumab plus methotrexate ( MTX ) therapy in patients with early RA . Methods . PREMIER was a phase III , multicenter , r and omized , double-blind , active-comparator clinical trial in early RA . Patients aged ≥ 18 years were r and omly assigned to receive adalimumab 40 mg every other week ( eow ) plus weekly MTX , weekly MTX , or adalimumab 40 mg eow for 104 weeks . American College of Rheumatology ( ACR ) criteria were used to evaluate clinical efficacy and response . Outcomes were assessed using the Health Assessment Question naire Disability Index ( HAQ-DI ) , Short-Form 36 Health Survey ( SF-36 ) , Short-Form 6 Dimension ( SF-6D ) , visual analog scale ( VAS ) assessment s of global disease activity ( patient ’s global assessment ; PtGA ) and pain , Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) , and Health Utility Index Mark 3 ( HUI-3 ) . Results . Of 799 patients enrolled , 268  received adalimumab plus MTX , 257 received MTX monotherapy , and 274 received adalimumab monotherapy . Patients treated with adalimumab plus MTX demonstrated significant baseline to Week 104 improvements in HAQ-DI ( p < 0.0001 ) , SF-36 Physical Component Summary ( p < 0.0001 ) , 4 SF-36 domains [ physical function ( p < 0.0001 ) , bodily pain ( p < 0.0001 ) , vitality ( p = 0.0139 ) , role limitations -physical ( p = 0.0005 ) ] , SF-6D ( p = 0.0152 ) , VAS-PtGA ( p < 0.0001 ) , VAS-pain ( p < 0.0001 ) , FACIT-F ( p < 0.0001 ) , and HUI-3 ( p = 0.0034 ) scores versus patients treated with MTX monotherapy . Both SF-6D and HUI-3 were found to be sensitive preference-based measures for assessing the effects of treatment on multidimensional function . No clinical ly meaningful differences between adalimumab and MTX monotherapy groups were observed for most measures . For each measure , there was significant association between HRQOL improvement and ACR clinical response . Conclusion . Adalimumab plus MTX significantly improved physical functioning and HRQOL in patients with early RA over 2 years of treatment . ( Clinical Trials.gov identifier NCT00195663 ) Objectives : To investigate the levels of interleukin (IL)-23 in patients with early rheumatoid arthritis ( eRA ) and the effect of anti-tumour necrosis factor (anti-TNF)-α treatment on IL-23 levels . Method : Treatment-naïve eRA patients from the OPERA cohort were included ( n = 151 ) . Patients were r and omized to methotrexate ( MTX ) plus adalimumab ( ADA ; n = 75 ) or MTX plus placebo-ADA ( PLA ; n = 76 ) . Plasma sample s were obtained at baseline and at months 3 , 6 , and 12 together with values for C-reactive protein ( CRP ) , the 28-joint Disease Activity Score based on CRP ( DAS28CRP ) , scores on the Clinical Disease Activity Index ( CDAI ) and the Simplified Disease Activity Index ( SDAI ) , visual analogue scale ( VAS ) for pain/fatigue/physician global and total Sharp/van der Heijde score ( TSS ) . IL-23 was measured at each time point . Results : IL-23 levels decreased significantly in the ADA group from 20.6 pg/mL ( IQR 13.1–32.7 pg/mL ) at baseline to 18 pg/mL ( IQR 7.2–25.0 pg/mL ) at 12 months ( p < 0.01 ) . No significant decrease in IL-23 level was observed in the PLA group . No associations between baseline IL-23 levels and measures of disease activity ( DAS28CRP , CRP , CDAI , or SDAI ) at 12 or 24 months were present in the treatment groups . Baseline IL-23 correlated inversely with changes in TSS and symptom duration before diagnosis . Conclusions : Our data show increased baseline levels and a significant decrease in IL-23 levels in eRA patients  treated with anti-TNF-α . The inverse correlation with duration of symptoms before diagnosis supports the importance of IL-23 in the pre clinical disease development of RA Context A treat-to-target strategy , or treatment to achieve low disease activity , has been associated with improved outcomes among patients with early active rheumatoid arthritis ( RA ) . Long-term data on this approach are lacking . Contribution This r and omized , controlled trial compared 4 treat-to-target strategies for early active RA over 10 years . Most patients had persistently reduced disease activity scores , improved functional status , and limited joint damage during follow-up . They had survival similar to that of the general Dutch population . Caution The trial lacked a nontargeted treatment strategy . Implication Potential outcomes of a treat-to-target approach for early RA include sustained clinical improvement , drug-free remission , and normalized survival . Suppression of inflammation in patients with rheumatoid arthritis ( RA ) is associated with clinical improvement and prevention of radiographic joint damage . Rapid suppression can be achieved with initial combination therapy , including synthetic disease-modifying antirheumatic drugs and corticosteroids or a tumor necrosis factor- inhibitor ( 17 ) . In addition , tightly controlled targeted treatment ( that is , frequent measurements of disease activity with treatment adjustments aim ing to achieve a predefined target ) results in better outcomes than routine care ( 8 , 9 ) . The BeSt ( Beh and elStrategien in reumatode artritis ) study integrated a treat-to-target concept to achieve low disease activity ( defined as a disease activity score [ DAS ] 2.4 ) with a comparison of 4 dynamic treatment strategies . Patients with early active RA were r and omly assigned to sequential monotherapy , step-up combination therapy , or initial combination therapy with either prednisone or an antitumor necrosis factor- agent ( infliximab ) . Based on measurements of disease activity every 3 months , the medication dosage was increased when the DAS was higher than 2.4 and tapered if DAS was persistently 2.4 or less . The study compared the clinical , radiographic , and toxicity outcomes of these strategies over time . We report on these outcomes among participants during 10-year follow-up and compare their survival with that of the general population . Methods Design Overview The r and omized , multicenter , assessor-blinded BeSt study ( 2 ) was design ed by Dutch rheumatologists to determine in which order available antirheumatic medication could best be used to treat patients with newly diagnosed RA , aim ing at low disease activity over 10 years . The original study protocol and amendments for study extension after 2 and 5 years ( Supplements 1 through 3 ) were approved by the medical ethics committees of all participating hospitals . All patients gave written informed consent . Supplement . Data Supplement Setting and Participants The study enrolled 508 patients aged 18 years or older with early active RA according to the revised 1987 American College of Rheumatology criteria for RA ( 10 ) , with symptom duration of fewer than 2 years . They were recruited in 18 nonuniversity and 2 university hospitals in the Netherl and s between 2000 and 2002 . Exclusion criteria encompassed contraindications to the antirheumatic medications used in the study protocol ( Appendix 1 ) ( 2 , 11 ) . R and omization and Interventions Patients were allocated to 1 of 4 dynamic treatment strategies by variable block r and omization , stratified by center : strategy 1 , sequential monotherapy ; strategy 2 , step-up combination therapy ( both starting with methotrexate monotherapy ) ; strategy 3 ; initial combination therapy with methotrexate , sulfasalazine , and prednisone ; and strategy 4 , initial combination therapy with methotrexate and infliximab . For all strategies , subsequent treatment adjustments were specified in the study protocol for patients with an inadequate response ( Appendix Figure 1 ) . Over 10 years , treatment response was measured every 3 months using the DAS ( 12 ) based on a swollen joint count in 44 joints , a tender joint count in 53 joints ( Ritchie articular index ) ( 13 ) , erythrocyte sedimentation rate , and patient 's assessment of global health on a visual analogue scale ( 0 to 100 mm ) ( 12 ) . A DAS of 2.4 or less , indicating low disease activity ( 14 ) , was set as the treatment goal . Treatment was intensified ( medication changed or dosage increased , according to the treatment strategy ) at each study visit that the DAS was greater than 2.4 ( Appendix Figure 1 ) . In case of a continued good response ( DAS 2.4 for 6 months ) , dosage was tapered to a maintenance dose ( if DAS remained < 1.6 for 6 months ; defined as remission ) ( 15 ) and eventually discontinued ( defined as drug-free remission [ DFR ] ) ( Appendix 2 ) . Appendix Figure 1 . Flow diagram of treatment steps per strategy . The figure shows the required treatment intensification steps for each strategy as long as the DAS remained > 2.4 when measured every 3 mo . In all 4 strategies , patients may progress from one treatment step to the next at different times , depending on individual DAS results determined at observation every 3 mo . Patients receiving infliximab ( who receive their dose every 8 wk ) had additional DAS measurements 1 wk before each infusion . These measurements dictated if the next dose needed to be increased . Doses started at 3 mg/kg of body weight . If the DAS was greater than 2.4 , the dose was increased in a stepwise manner to 6 mg/kg , then 7.5 mg/kg , and finally 10 mg/kg ( always rounded to the nearest hundredth ) . The dosage could be tapered if DAS calculations determined every 3 mo were 2.4 or less for at least 6 mo consecutively . Medication dosages were as follows : azathioprine , 2 mg/kg to 3 mg/kg per day ; cyclosporine A , 2.5 mg/kg per day ; methylprednisolone , 3 doses of 120 mg in weeks 1 , 4 , and 8 ; gold , 50 mg/wk ; hydroxychloroquine , 200 mg/d ; infliximab , dose as indicated every 8 wk ; leflunomide , 20 mg/d ; methotrexate , dose as indicated every week ; prednisone , 7.5 mg/d unless indicated otherwise ; sulfasalazine , 2000 mg/d .  DAS= disease activity score . Outcomes and Follow-up The patients were clinical ly assessed every 3 months at study visits during the 10-year follow-up . Functional status , laboratory tests , and adverse events ( AEs ) were assessed . Functional ability was measured using the Health Assessment Question naire ( HAQ ) ( range , 0 [ best ] to 3 [ worst ] ) ( 16 ) . Conventional radiography of h and s and feet were performed annually to assess joint damage progression . All radiographs from baseline to year 10 were scored by 2 independent blinded readers using the modified Sharpvan der Heijde score ( SHS ) ( range 0 [ best ] to 448 [ worst ] ) ( 17 ) in 1 session in r and om order . The intraclass correlation coefficient between the 2 readers was 0.96 ( 95 % CI , 0.95 to 0.97 ) . The mean score of the 2 readers was used for the analysis . The AEs , either reported during visits or apparent in continued laboratory assessment s every 3 months , and serious AEs ( SAEs ) , which also included death during follow-up , were recorded during the trial . For patients who dropped out of the study , life and death status from inclusion to year 10 was obtained from the hospital ( where they enrolled ) , general practitioner , or municipality of the patient 's residence . Those who emigrated and could not be traced thereafter were censored from the date of emigration ( n= 6 ) . One patient could not be located after loss to follow-up and was also censored from the last moment of contact . Survival data of the general Dutch population were acquired from Statistics Netherl and s. Statistical Analysis For each analysis , patients were analyzed in their allocated treatment strategy at baseline , regardless of the number of treatment steps during follow-up . Time to dropout was compared among the treatment strategies with the log-rank test . The HAQ score , low disease activity , remission rate , DFR , SHS , and initial treatment step at year 10 ( intention-to-treat and completer analyses ) were reported separately for each strategy . After multiple imputation of the DAS , the percentages of low disease activity ( DAS 2.4 ) and remission ( DAS < 1.6 ) at year 10 were estimated and compared among the strategies . The imputation model included terms for observed DAS , HAQ score , r and omization strategy , age , sex , anticitrullinated peptide antibody , rheumatoid factor , SHS , and treatment step ; 10 data sets were imputed ( Supplement 4 ) . The imputation method assumed the missing values to be missing at r and om . Sensitivity analyses using controlled imputation methods ( 18 ) tested the robustness of this assumption against violations ( Supplement 4 ) . The HAQ score was analyzed over time using a linear mixed model , taking into account repeated measurements , with a Toeplitz covariance type under the assumption of equally spaced visits ( scheduled every 3 months ) . This model included time as a continuous variable , treatment , and a time-by-treatment interaction term . Sensitivity analyses were also performed for this outcome ( Supplement 4 ) . Radiographic progression at 10 years ( defined as an increase in SHS from baseline to year 10 ) was observed in patients who completed the study using a cumulative probability plot . Radiographic progression over time was analyzed by using a weighted generalized estimating equation ( GEE ) with a negative binomial working distribution , AR1 ( that is , autoregressive ) working correlation , and robust estimation of SEs . This analysis is valid under the missing-at-r and om assumption and was chosen because of the skewed nature of the SHS ( 18 ) . Weights per patient per year were found by using a logistic regression that modeled the inverse probability of a patient having radiographic data available at that measurement time ( Supplement 5 ) . Survival in the study population was compared with the general population ( matched by sex , age , and calendar year ) using the st and ardized mortality ratio : ( observed deathsexpected deaths ) ( 19 ) . KaplanMeier curves and the log-rank test were used to compare survival among the treatment strategies . Cox regression analysis was used to identify Objective . The aim was to identify plasma ( i.e. , cell-free ) microRNA ( miRNA ) predicting  antitumor necrosis and /or methotrexate ( MTX )  treatment response in patients enrolled in an investigator-initiated , prospect i ve , double-blinded , placebo-controlled trial ( The OPERA study , NCT00660647 ) . Methods . We included 180 disease-modifying antirheumatic drug – naive patients with early rheumatoid arthritis ( RA ) r and omized to adalimumab ( ADA ; n = 89 ) or placebo ( n = 91 ) in combination with MTX .  Plasma sample s before and 3 months after treatment initiation were analyzed for 91 specific miRNA by quantitative reverse transcriptase-polymerase chain reaction on microfluidic dynamic arrays . A linear mixed-effects model was used to test for associations between pretreatment miRNA and changes in miRNA expression and American College of Rheumatology/European League Against Rheumatism ( ACR/EULAR ) Boolean ( 28 joints ) remission at 3 and 12 months , applying false discovery rate correction for multiple testing . Using leave-one-out cross validation , we built predictive multivariate miRNA models and estimated classification performances using receiver-operating characteristics ( ROC ) curves . Results . In the ADA group , a higher pretreatment level of miR-27a-3p was significantly associated with remission at 12 months . The level decreased in remitting patients between pretreatment and 3 months , and increased in nonremitting patients . No associations were found in the placebo group receiving only MTX . Two multivariate miRNA models were able to predict response to ADA treatment after 3 and 12 months , with 63 % and 82 % area under the ROC curves , respectively . Conclusion . We identified miR-27a-3p as a potential predictive biomarker of ACR/EULAR remission in patients with early RA treated with ADA in combination with MTX . We conclude that pretreatment plasma-miRNA profiles may be of predictive value , but the results need confirmation in independent cohorts Objectives : Measurement of serum biomarkers at disease onset may improve prediction of disease course in patients with early rheumatoid arthritis ( RA ) . We evaluated the multi-biomarker disease activity ( MBDA ) score and early changes in MBDA score for prediction of 28-joint Disease Activity Score based on C-reactive protein ( DAS28-CRP ) remission and radiographic progression in the double-blinded OPERA trial . Method : Treatment-naïve RA patients ( N = 180 ) with moderate or high DAS28 were r and omized to methotrexate ( MTX ) + adalimumab ( n = 89 ) or MTX + placebo ( n = 91 ) in combination with glucocorticoid injection into swollen joints . X-rays of h and s and feet were evaluated at months 0 and 12 ( n = 164 ) by the total Sharp van der Heijde score ( TSS ) . The smallest detectable change ( 1.8 TSS units ) defined radiographic progression ( ∆TSS ≥ 2 ) . Clinical remission ( DAS28-CRP < 2.6 ) was assessed at baseline and 6 months . MBDA score was determined at 0 and 3 months and tested in a multivariable logistic regression model for predicting DAS28 remission at 6 months and radiographic progression at 1 year . Results : Baseline MBDA score was independently associated with radiographic progression at 1 year [ odds ratio ( OR ) = 1.03/unit , 95 % confidence interval ( CI ) = 1.01–1.06 ] , and changes in MBDA score from baseline to 3 months with clinical remission at 6 months [ OR = 0.98/unit , 95 % CI 0.96–1.00 ) . In anti-cyclic citrullinated peptide antibody (anti-CCP)-positive patients , 35 of 89 with high MBDA score ( > 44 ) showed radiographic progression ( PPV = 39 % ) , compared with 0 of 15 patients ( NPV = 100 % ) with low/moderate MBDA score ( ≤ 44 ) ( p = 0.003 ) . Conclusion : Early changes in MBDA score were associated with clinical remission based on DAS28-CRP at 6 months . In anti-CCP-positive patients , a non-high baseline MBDA score ( ≤ 44 ) had a clinical value by predicting very low risk of radiographic progression at 12 months Background In the present study , we explored the effects of immediate induction therapy with the anti-tumour necrosis factor (TNF)α antibody infliximab ( IFX ) plus methotrexate ( MTX ) compared with MTX alone and with placebo ( PL ) in patients with very early inflammatory arthritis . Methods In an investigator-initiated , double-blind , r and omised , placebo-controlled , multi-centre trial ( IS RCT N21272423 , http://www.is rct n.com/IS RCT N21272423 ) , patients with synovitis of 12 weeks duration in at least two joints underwent 1 year of treatment with IFX  in combination with MTX , MTX monotherapy , or PL r and omised in a 2:2:1 ratio . The primary endpoint was clinical remission after 1 year ( sustained for at least two consecutive visits 8 weeks apart ) with remission defined as no swollen joints , 0–2 tender joints , and an acute-phase reactant within the normal range . Results Ninety patients participated in the present study . At week 54 ( primary endpoint ) , 32 % of the patients in the IFX + MTX group achieved sustained remission compared with 14 % on MTX alone and 0 % on PL . This difference ( p < 0.05 over all three groups ) was statistically significant for IFX + MTX vs PL ( p < 0.05 ) , but not for IFX + MTX vs MTX ( p = 0.10 ) , nor for MTX vs PL ( p = 0.31 ) . Remission was maintained during the second year on no therapy in 75 % of the IFX + MTX patients compared with 20 % of the MTX-only patients . Conclusions These results indicate that patients with early arthritis can benefit from induction therapy with anti-TNF plus MTX compared with MTX alone , suggesting that intensive treatment can alter the disease evolution . Trial registration The trial was registered at http://www.is rct n.com/IS RCT N21272423 on 4 October 2007 ( date applied)/12 December 2007 ( date assigned ) . The first patient was included on 24 October 2007 OBJECTIVES To evaluate the effects of adalimumab plus MTX ( ADA + MTX ) vs MTX monotherapy on work-related outcomes in early RA patients with elevated risk of employment loss . METHODS A post hoc analysis at weeks 26 and 24 from the Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab ( OPTIMA ) and PRevention Of Work Disability ( PROWD ) trials , respectively , was conducted in  MTX-naïve RA patients r and omized to ADA + MTX or placebo ( PBO ) + MTX .  Work instability was assessed using the RA-Work Instability Scale ( RA-WIS ) and work productivity was measured with the Work Productivity and Activity Impairment Question naire . Employed patients with a baseline RA-WIS score ⩾10 , indicating medium to high risk for job loss , were included ( OPTIMA , n = 320 ; PROWD , n = 124 ) . RESULTS Patients receiving ADA + MTX in OPTIMA had significantly greater improvements in RA-WIS compared with PBO + MTX ( mean change -7.22 vs -5.23 , respectively ) . Significantly higher percentages of patients in the ADA + MTX group experienced improvements in one or more risk category ( 58 vs 47 % ) and ⩾5 ( 55 vs 43 % ) , ⩾7 ( 47 vs 35 % ) and ⩾9 ( 42 % vs 26 % ) points in their RA-WIS score . These trends were seen in PROWD but were not significant . In OPTIMA , patients receiving ADA + MTX showed significant changes in percentage points from baseline vs PBO + MTX  in activity impairment , presenteeism and overall work impairment ( -32.0 vs -23.7 , -24.6 vs -17.1 , -27.3 vs -18.3 , respectively ) . CONCLUSIONS Among early RA patients with elevated risk of employment loss , ADA + MTX therapy was associated with a significant reduction in work  instability vs PBO + MTX . Significantly greater percentages of patients receiving ADA + MTX therapy achieved clinical ly meaningful improvements in their RA-WIS scores Objective To evaluate the construct validity of the rheumatoid arthritis MRI score ( RAMRIS ) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials . Methods In a r and omised trial of early methotrexate-naïve RA ( GO-BEFORE ) , RAMRIS scores were determined from MRIs and van der Heijde-Sharp ( vdHS ) scores from radiographs , at baseline , week 12 , week 24 and week 52 . Progression in damage scores was defined as change > 0.5 . Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity . Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy ( methotrexate+golimumab ) and methotrexate-monotherapy arms in ( A ) change in damage score and ( B ) proportion of patients progressing . Results Patients with early MRI progression had higher DAS28 , C reactive protein ( CRP ) and vdHS at baseline , and higher 2-year HAQ . Associations were similar to those with 1-year vdHS progression . Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome ( 150 patients ; 100 among an enriched sample with baseline-synovitis > 5 ) compared with the 52-week vdHS ( 275 patients ) . Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects . Conclusions Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials
Introduction Synthesis of evidence on the long-term use of first-line biologic therapy in patients with early rheumatoid arthritis ( RA ) is required .
We compared the efficacy of up to 5 years ’ treatment with first-line tumor necrosis factor inhibitors ( TNFis ) versus other treatment strategies in this population .