Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA) Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register Evaluation of the Quality of Prognosis Studies in Systematic Reviews Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab Infliximab in ankylosing spondylitis: alone or in combination with methotrexate? A pharmacokinetic comparative study TNFα blockade prevents the development of inflammatory bowel disease in HLA-B27 transgenic rats Erythrocyte sedimentation rate, C-reactive protein level, and serum amyloid a protein for patient selection and monitoring of anti-tumor necrosis factor treatment in ankylosing spondylitis. Remission in psoriatic arthritis: is it possible and how can it be predicted? Serum markers associated with clinical improvement in patients with ankylosing spondylitis treated with golimumab Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial. Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register. Obesity and the prediction of minimal disease activity: A prospective study in psoriatic arthritis Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial Prediction of major clinical response (ACR50) to infliximab in psoriatic arthritis refractory to methotrexate Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Baseline factors that influence ASAS 20 response in patients with ankylosing spondylitis treated with etanercept. Body mass index influences the response to infliximab in ankylosing spondylitis Risk factors for radiographic progression in psoriatic arthritis: subanalysis of the randomized controlled trial ADEPT Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial Response to one infusion predicts subsequent improvement as well as the rate of relapse of ankylosing spondylitis infused with three pulses of infliximab Increased efficacy of infliximab associated with methotrexate in ankylosing spondylitis. Time and predictors of response to tumour necrosis factor-alpha blockers in psoriatic arthritis: an analysis of a longitudinal observational cohort. Body mass does not affect the remission of psoriatic arthritis patients on anti-TNF-α therapy Clinical manifestations and responsiveness to adalimumab are similar in patients with ankylosing spondylitis with and without concomitant psoriasis. MRI in predicting a major clinical response to anti-tumour necrosis factor treatment in ankylosing spondylitis. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Effectiveness, Safety, and Predictors of Good Clinical Response in 1250 Patients Treated with Adalimumab for Active Ankylosing Spondylitis Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Efficacy and tolerability of anti-tumour necrosis factor therapy in psoriatic arthritis patients: results from the South Swedish Arthritis Treatment Group register Serum MMP-3 Level as a Biomarker for Monitoring and Predicting Response to Etanercept Treatment in Ankylosing Spondylitis Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years' surveillance in the Danish nationwide DANBIO registry ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Adalimumab or Cyclosporine as Monotherapy and in Combination in Severe Psoriatic Arthritis: Results from a Prospective 12-month Nonrandomized Unblinded Clinical Trial Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor α therapy: results from the nationwide Danish DANBIO registry.
Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-PsA ( NCT01087788 ) , an ongoing Phase 3 trial in patients with psoriatic arthritis ( PsA ) . Methods Patients were r and omised 1:1:1 to placebo  , 200 mg CZP every 2 weeks ( Q2W ) or 400 mg CZP every 4 weeks ( Q4W ) . Patients could have had exposure to one previous tumour necrosis factor ( TNF ) inhibitor therapy . Primary endpoints were American College of Rheumatology 20 % ( ACR20 ) response at week 12 and modified Total Sharp Score change from baseline at week 24 . Secondary endpoints included ; Psoriatic Arthritis Response Criteria ( PsARC ) score , Health Assessment Question naire Disability Index ( HAQ-DI ) , Psoriasis Area and Severity Index , Leeds Enthesitis Index , Leeds Dactylitis Index , and Modified Nail Psoriasis Severity Index . Results Of 409 patients r and omised , 368 completed 24 weeks of treatment .  ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo ( 58.0 % and 51.9 % vs 24.3 % ( p<0.001 ) ) at week 12 , with improvements observed by week 1 . There was a statistically significant improvement in physical function from baseline , measured by HAQ-DI in CZP patients compared with placebo ( −0.50 vs −0.19 , p<0.001 ) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo ( 78.3 % and 77.0 % vs 33.1 % ( p<0.001 ) ) . Sustained improvements were observed in psoriatic skin involvement , enthesitis , dactylitis and nail disease . Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure . No new safety signals were observed . Conclusions Rapid improvements in the signs and symptoms of PsA , including joints , skin , enthesitis , dactylitis and nail disease were observed across both CZP dosing regimens Objective . Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK . This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) and Bath Ankylosing Spondylitis Functional Index ( BASFI ) after 6 months of therapy in 261 patients enrolled in a national prospect i ve observational register . Methods . The British Society for Rheumatology Biologics Register ( BSRBR ) recruited patients starting anti-TNF therapy for AS between 2002 and 2006 . Multivariable linear regression models were used to estimate the predictors of absolute improvement in BASDAI and BASFI at 6 months . Covariates included age , gender , disease duration , baseline BASDAI and BASFI , presence of raised inflammatory markers ( defined as twice the upper limit of normal ) and DMARD therapy . Results . The cohort was young ( median age 43 years ) and 82 % were males .  Median baseline BASDAI was 7.6 and BASFI 7.9 . At 6 months , the mean improvements in BASDAI and BASFI were 3.6 and 2.6 U , respectively ; 52 % reached a BASDAI50 . Patients with raised inflammatory markers at the start of therapy had a 0.9-U ( 95 % CI 0.2 , 1.5 ) better improvement in BASDAI compared with those without . Lesser responses were seen in those with higher baseline BASFI scores . Women had a 1.1-U ( 95 % CI 0.3 , 2.0 ) greater improvement in BASFI at 6 months , as did those who were receiving concurrent DMARD therapy [ 0.9 U ( 95 % CI 0.2 , 1.7 ) ] . Conclusions . The majority of patients receiving anti-TNF therapy for AS during routine care demonstrated an improvement in disease activity . Raised inflammatory markers at the start of therapy predicted a greater improvement in BASDAI , identifying a group of patients who may be more responsive to anti-TNF therapies , although the results were not confined to this group Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Objective To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis ( PsA ) . Methods GO – REVEAL was a r and omised , placebo-controlled study of golimumab in patients with active PsA. Sample s were collected from 100 patients at baseline , week 4 and week 14 , and analysed for serum-based biomarkers and protein profiling ( total 92 markers ) ; data were correlated with clinical measures at week 14 . Results Serum levels of a subset of proteins ( apolipoprotein C III , ENRAGE , IL-16 , myeloperoxidase , vascular endothelial growth factor , pyridinoline , matrix metalloproteinase 3 , C-reactive protein ( CRP ) , carcinoembryonic antigen , intercellular adhesion molecule 1 and macrophage inflammatory protein 1α ) at baseline or week 4 were strongly associated with American College of Rheumatology 20 % improvement ( ACR20 ) response and /or disease activity score in 28 joints ( DAS28 ) at week 14 . A smaller subset of proteins was significantly associated with a 75 % improvement in the psoriasis area and severity index score ( PASI75 ) at week 14 , ( adiponectin , apolipoprotein CIII , serum glutamic oxaloacetic transaminase , and tumour necrosis factor α ) . Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures , and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone . Conclusions This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have  ACR20 , DAS28 , or PASI75  responses  following golimumab treatment Introduction Methotrexate ( MTX ) has been shown to modify infliximab pharmacokinetics in rheumatoid arthritis . However , its combination with infliximab in the treatment of ankylosing spondylitis ( AS ) is not recommended . The objective of this study was to examine the influence of MTX on infliximab exposure in patients with AS . Methods Patients with AS patients who had predominantly axial symptoms were r and omised to receive infliximab alone ( infusions of 5 mg/kg at weeks 0 , 2 , 6 , 12 and 18 ) or infliximab combined with MTX ( 10 mg/week ) .  Infliximab concentrations were measured before and 2 hours after each infusion and at 1 , 3 , 4 , 5 , 8 , 10 , 14 and 18 weeks . We estimated individual cumulative area under the concentration versus time curves ( AUC ) for  infliximab concentration between baseline and week 18 ( AUC0 - 18 ) . Clinical and laboratory evaluations were performed at each visit . The Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score was the primary end point for clinical response . Results Twenty-six patients were included  ( infliximab group : n = 12 , infliximab + MTX group : n = 14 ) , and 507 serum sample s were available for measurement of  infliximab concentration . The two groups did not differ with regard to AUC0 - 18 or evolution of BASDAI scores and biomarkers of inflammation . Conclusions The combination of MTX and infliximab does not increase the exposure to infliximab over infliximab alone in patients with AS.Trial registration Clinical Trials.gov : Abstract Rats transgenic for HLA-B27 and human β2microglobulin ( B27TR ) develop a multi-systemic disease resembling inflammatory bowel disease ( IBD ) and spondyloarthritis . TNFα has a crucial role in chronic inflammation . Our objective was to evaluate the effect of anti-TNFα treatment on spontaneous IBD in B27TR . Nine-week-old B27TR  received monoclonal anti-TNFα or an isotypic IgG2a , k up to age of 18 weeks . A second group was monitored up to 18 weeks and then r and omly assigned to anti-TNFα or IgG2 a , k treatment . Each rat was monitored for clinical IBD manifestations . After sacrifice , the colon was examined for pathological changes . TNFα receptors ( TNF-R1 , TNF-R2 ) , Fas/Fas-L expression and apoptosis were evaluated . IgG2a , k-treated and untreated B27TR presented signs of IBD at 11 weeks , whereas in anti-TNFα-treated B27TR no IBD signs were detected . In the late treatment , IBD signs improved after 1 week . Histopathological analysis of IgG2a , k-treated B27TR colon showed inflammatory signs that were widely prevented by early anti-TNFα treatment . Late treatment did not significantly reduce inflammation . TNF-R1 was weakly expressed in intestinal epithelial cells of IgG2a , k-treated B27TR , while it was comparable to controls in anti-TNFα-treated animals . TNF-R2 immunopositivity was strongly evident in IgG2a , k-treated B27TR , whereas was absent in anti-TNFα-treated rats . RT-PCR confirmed these results . IgG2a , k-treated B27TR showed , at 18 weeks , few Fas-positive cells and an increase of Fas-L-positive cells . At 27 weeks , Fas-/Fas-L-positive cell number was significantly low . Anti-TNFα  treatment increased Fas-L expression , whereas Fas increased only with the early treatment . TNFα blockade is effective in preventing inflammation in early phase of IBD , maintaining the homeostatic balance of apoptosis OBJECTIVE To study the usefulness of erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , and serum amyloid A ( SAA ) for response prediction and monitoring of anti-tumor necrosis factor ( anti-TNF ) treatment in ankylosing spondylitis ( AS ) patients . METHODS Patients were included consecutively before starting etanercept or infliximab treatment .  ASsessment in Ankylosing Spondylitis ( ASAS ) response , defined as a 50 % improvement or an absolute improvement of 2 points of the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ; 0 - 10 scale ) , was assessed at 3 months . Inflammatory markers and the BASDAI were collected at baseline and 1 and 3 months . Longitudinal data analysis was performed to compare associations between inflammatory markers and the BASDAI over time by calculating st and ardized betas . Predictive values of baseline levels of inflammatory markers for ASAS response were calculated . RESULTS In total , 155 patients were included , of whom , after 3 months of treatment , 70 % in the etanercept cohort and 71 % in the infliximab cohort responded . All markers , notably SAA , decreased significantly ( P < 0.0001 ) . St and ardized betas were 0.49 for ESR , 0.43 for CRP , and 0.39 for SAA . Normal baseline levels of CRP and SAA were significantly associated with nonresponse . A combination of elevated CRP and SAA levels at baseline revealed the highest predictive value ( 81 % ) for ASAS response . CONCLUSION ESR , CRP , and SAA were significantly associated with the BASDAI over 3 months , and the association with ESR was the strongest . Elevated baseline CRP and SAA levels revealed the highest predictive value for response . Together , this study demonstrates that inflammatory markers , and notably CRP and SAA , may facilitate patient selection and monitoring of efficacy of anti-TNF treatment in AS , and could be added to response criteria Introduction Since remission is now possible in psoriatic arthritis ( PsA ) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha ( TNFα ) therapy  and to examine possible predictors of response . Methods Analysis of a prospect i ve patient cohort attending a biologic clinic , between November 2004 and March 2008 , was performed prior to commencing therapy and at regular intervals . Baseline clinical characteristics including demographics , previous disease-modifying antirheumatic drug ( DMARD ) response , tender and swollen joint counts , early morning stiffness , pain visual analogue score , patient global assessment , C reactive protein ( CRP ) and health assessment question naire ( HAQ )  were collected . Results A total of 473 patients ( 152 PsA ; 321 rheumatoid arthritis ( RA ) ) were analyzed . At 12 months remission , defined according to the disease activity score using 28 joint count and CRP ( DAS28-CRP ) , was achieved in 58 % of PsA patients compared to 44 % of RA patients , significant improvement in outcome measures were noted in both groups ( P < 0.05 ) . Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission . Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients ( P < 0.001 ) . Conclusions DAS28 remission is possible in PsA patients at one year following anti-TNF therapy , at higher rates than in RA patients and is predicted by baseline HAQ Objective Identify serum biomarkers modulated by golimumab treatment and associated with clinical response in patients with ankylosing spondylitis ( AS ) . Methods Sera were collected at weeks 0 , 4 and 14 from 100 patients with active AS in the GO – RAISE study . Patients were r and omly assigned subcutaneous injections of placebo , golimumab 50 mg , or golimumab 100 mg every 4 weeks . Sample s were tested for select inflammatory , bone and cartilage markers , and protein profiling was also performed . Results Golimumab treatment result ed in significant decreases in several serum proteins at weeks 4 and 14 compared with placebo . Patients who achieved clinical response at week 14 , as assessed by a ≥20 % improvement in the Assessment in SpondyloArthitis international Society response criteria ( ASAS 20 ) , demonstrated a distinct biomarker profile with lower levels of acute phase reactants and inflammatory biomarkers compared with patients who did not . Notably , combinations of two or three biomarkers assessed at baseline were predictive of various clinical outcomes ( ASAS 20 , Bath ankylosing spondylitis disease activity index 50 or Bath ankylosing spondylitis functional index ) using a logistic regression analysis , and the overall predictive values for these combined biomarkers were greater than observed for C-reactive protein ( CRP ) alone . Conclusion Golimumab modulated acute phase reactants and inflammatory markers in patients with active AS . Specific combinations of biomarkers at baseline demonstrated a stronger prediction for clinical efficacy than CRP alone . These data provide insights into the mechanism of golimumab on inflammatory processes driving AS pathology , and may have utility in managing the treatment of patients with AS Objective : To evaluate the efficacy and safety of infliximab through 1 year in patients with psoriatic arthritis ( PsA ) enrolled in the IMPACT 2 trial . Methods : In this double blind , placebo controlled , phase III study , 200 patients with active PsA were r and omised to receive infusions of infliximab 5 mg/kg or placebo at weeks 0 , 2 , 6 , and every 8 weeks thereafter through 1 year . Patients with persistent disease activity could enter early escape at week 16 , and all remaining placebo patients crossed over to infliximab at week 24 . Patients r and omised to infliximab who had no response or who lost response could escalate their dose to 10 mg/kg starting at week 38 . Clinical efficacy was assessed based on the proportion of patients achieving ACR 20 and PASI 75 responses . Major clinical response ( that is , maintenance of ACR 70 response for 24 continuous weeks ) was assessed for the first time in PsA. Results : Through 1 year of treatment , 58.9 % and 61.4 % of patients in the r and omised infliximab and placebo/infliximab groups , respectively , achieved ACR 20 ; corresponding figures for PASI 75 were 50.0 % and 60.3 % . At week 54 , major clinical response was achieved by 12.1 % of patients in the infliximab group . The safety profile of infliximab through week 54 was consistent with that seen through week 24 . Two malignancies occurred : basal cell skin cancer ( placebo ) and stage I Hodgkin ’s lymphoma ( infliximab ) . Conclusion : Infliximab maintains a high degree of clinical efficacy and continues to be well tolerated in patients with PsA through 1 year of treatment OBJECTIVES To evaluate further in a phase III , double blind trial the efficacy of infliximab in patients with active psoriatic arthritis ( PsA ) , as observed in the smaller IMPACT trial . METHODS 200 patients with active PsA unresponsive to previous treatment were r and omised to infusions of infliximab 5 mg/kg or placebo at weeks 0 , 2 , 6 , 14 , and 22 . Patients with inadequate response entered early escape at week 16 . The primary measure of clinical response was ACR20 . Other measures included Psoriatic Arthritis Response Criteria ( PsARC ) , Psoriasis Area and Severity Index ( PASI ) , and dactylitis and enthesopathy assessment s. RESULTS At week 14 , 58 % of patients receiving infliximab and 11 % of those receiving placebo achieved an ACR20 response and 77 % of infliximab patients and 27 % of placebo patients achieved PsARC ( both p<0.001 ) . Among the 85 % of patients with at least 3 % body surface area psoriasis involvement at baseline , 53/83 ( 64 % ) patients receiving infliximab had at least 75 % improvement in PASI compared with 2/87 ( 2 % ) patients receiving placebo at week 14 ( p<0.001 ) . These therapeutic effects were maintained through the last evaluation ( week 24 ) . Fewer infliximab patients than placebo patients had dactylitis at week 14 ( 18 % v 30 % ; p = 0.025 ) and week 24 ( 12 % v 34 % ; p<0.001 ) . Fewer infliximab patients ( 22 % ) than placebo patients ( 34 % ) had active enthesopathy at week 14 ( p = 0.016 ) ; corresponding figures at week 24 were 20 % and 37 % ( p = 0.002 ) . Infliximab was generally well tolerated , with a similar incidence of adverse events in each group . CONCLUSIONS Infliximab 5 mg/kg through 24 weeks significantly improved active PsA , including dactylitis and enthesopathy , and associated psoriasis OBJECTIVE Golimumab , administered subcutaneously every 4 weeks , has been shown to be effective in reducing the signs and symptoms of active  psoriatic arthritis ( PsA ) through week 24 of the GO-REVEAL study . Herein we report 1-year clinical , radiographic , and safety findings . METHODS Adult patients with active PsA ( ≥3 swollen and ≥3 tender joints ) were r and omly assigned to receive subcutaneous placebo , golimumab 50 mg , or golimumab 100 mg every 4 weeks through week 20 . At week 16 , patients with < 10 % improvement from baseline  in swollen and tender joint counts entered a blinded early escape phase , with placebo crossover to golimumab 50 mg , golimumab 50 mg increased to 100 mg , and golimumab 100 mg continued at 100 mg . Patients receiving placebo who did not enter the early escape phase crossed over to golimumab 50 mg at week 24 . Findings through 1 year are reported , including the second of 2 co primary end points ( i.e. , change from baseline to week 24 in PsA-modified Sharp/van der Heijde score [ SHS ] ) . RESULTS A total of 405 patients were r and omized : 113 to placebo and 146 each to the golimumab 50 mg and 100 mg groups . Mean changes in PsA-modified SHS from baseline to week 24 for the combined golimumab 50 mg and 100 mg group ( -0.09 ) and the golimumab 50 mg group ( -0.16 ) were significantly different versus placebo ( 0.27 ) ( P = 0.015 and P = 0.011 , respectively ) . Radiographic benefit was maintained through week 52 with  golimumab . Clinical efficacy , including improvement in joint and skin responses and physical function , was maintained through 1 year . The frequency/types of adverse events were similar to those reported through week 24 . CONCLUSION Treatment of PsA with golimumab inhibited structural damage progression and demonstrated continued clinical efficacy and safety through 1 year OBJECTIVE To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences . METHODS Patients with active RA initiating their first treatment course of TNF-blocking therapy  were enrolled . The study period was March 1999 through September 2006 . The prospect i ve protocol included information on demographics , clinical characteristics of patients and response measures . Fulfilment of ACR 50 - 70 % improvement and European League Against Rheumatism ( EULAR ) good response or remission [ 28-joint disease activity score ( DAS28 ) < 2.6 ] at 3 months were chosen as primary outcome measures . Potential predictors of responses were identified using multivariate binary logistic regression models . RESULTS In total , 1565 patients were included in the study . Gender did not influence treatment response . Consistently , concomitant methotrexate ( MTX ) was significantly associated with EULAR remission , EULAR good response , ACR50 response and ACR70 response with odds ratios ( ORs ) 1.97 , 2.13 , 2.10 and 1.75 , respectively . Concurrent treatment with other DMARDs was also significantly associated with EULAR remission , EULAR good response and ACR50 response ( OR : 1.96 , 2.24 and 1.94 , respectively ) . Likewise , low HAQ at baseline consistently predicted good clinical outcome . Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 ( OR : 1.59 and 1.60 , respectively ) , whereas DAS28 score at baseline was inversely associated with EULAR remission ( OR : 0.78 ) . CONCLUSIONS In this observational study of patients with established RA , gender did not predict response to anti-TNF therapy , whereas treatment with concomitant DMARDs , especially MTX and low disability were associated with good response . Choice of outcome measures may influence the predictive value of baseline features We prospect ively evaluated whether obesity impacts achievement of minimal disease activity ( MDA ) in subjects with psoriatic arthritis ( PsA ) OBJECTIVE The signs and symptoms of ankylosing spondylitis ( AS ) respond inadequately to nonsteroidal antiinflammatory drugs , corticosteroids , and disease-modifying antirheumatic drugs in quite a number of patients . Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials . The objective of this multicenter , r and omized , placebo-controlled study was to evaluate the efficacy and safety of infliximab in patients with AS . METHODS Patients were r and omly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0 , 2 , 6 , 12 , and 18 . Efficacy was assessed using the ASsessment in Ankylosing Spondylitis ( ASAS ) International Working Group criteria , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , night pain , patient 's global assessment , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , the Bath Ankylosing Spondylitis Metrology Index ( BASMI ) , chest expansion , the M and er enthesis index , the total swollen joint index , the C-reactive protein level , and the Short Form 36 ( SF-36 ) health survey question naire . The primary end point in this study was the proportion of patients with a 20 % improvement response according to the ASAS International Working Group criteria ( ASAS20 responders ) at week 24 . RESULTS Of the 357 patients screened , 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo . After 24 weeks , 61.2 % of patients in the infliximab group were ASAS20 responders compared with 19.2 % of patients in the placebo group ( P < 0.001 ) . Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24-week study period . Patients receiving infliximab also showed significant improvements in the BASDAI , BASFI , BASMI , chest expansion , and physical component summary score of the SF-36 . Adverse events were reported by 82.2 % of patients receiving infliximab and by 72.0 % of patients receiving placebo ; however , most adverse events in both treatment groups were mild or moderate in severity . CONCLUSION Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24-week study period Objectives : To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis ( PsA ) and identify predictors of good clinical response for joint and skin lesions . Methods : Patients received adalimumab 40 mg every other week in addition to st and ard therapy in this prospect i ve , 12-week , open-label , uncontrolled study . Four definitions of good clinical response were used : ⩾50 % improvement in American College of Rheumatology response criteria ( ACR50 ) , good response according to European League Against Rheumatism ( EULAR ) guidelines , a ⩾3- grade improvement in Physician Global Assessment of psoriasis ( PGA ) and a ⩾50 % improvement in the Nail Psoriasis Severity Index ( NAPSI ) . Response predictors were determined by logistic regression with backward elimination ( selection level was 5 % ) . Results : Of 442 patients , 94 % completed 12 weeks of treatment . At week 12 , 74 % , 51 % and 32 % of the patients had achieved ACR20 , 50 and 70 , respectively ; 87 % and 61 % experienced moderate and good responses according to EULAR criteria , respectively . The percentage of patients with PGA results of “ clear/almost clear ” increased from 34 % ( baseline ) to 68 % . The mean NAPSI score was reduced by 44 % . No new safety signals were detected . A lower Health Assessment Question naire Disability Index ( HAQ-DI ) score , greater pain assessment , male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria . In addition , greater C-reactive protein concentration and polyarthritis predicted ACR50 , and non-involvement of large joints predicted a good response according to EULAR criteria . Conclusions : Adalimumab was effective in patients with PsA. Lower impairment of physical function , greater pain , male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response Introduction Identifying ankylosing spondylitis ( AS ) patients who are likely to benefit from tumor necrosis factor-alpha ( TNF-α ) blocking therapy  is important , especially in view of the costs and potential side effects of these agents . Recently , the AS Disease Activity Score ( ASDAS ) has been developed to assess both subjective and objective aspects of AS disease activity . However , data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking . The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice . Methods AS out patients who started TNF-α blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis ( GLAS ) study , an ongoing prospect i ve longitudinal observational cohort study with follow-up visits according to a fixed protocol . For the present analysis , patients were excluded if they had previously received anti-TNF-α treatment .  Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models , respectively . Results Between November 2004 and April 2010 , 220 patients started treatment with infliximab ( n = 32 ) , etanercept ( n = 137 ) , or adalimumab ( n = 51 ) . At three and six months , 68 % and 63 % of patients were Assessment s in Ankylosing Spondylitis (ASAS)20 responders , 49 % and 46 % ASAS40 responders , and 49 % and 50 % Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders , respectively . Baseline predictors of response were younger age , male gender , higher ASDAS score , higher erythrocyte sedimentation rate ( ESR ) level , higher C-reactive protein ( CRP ) level , presence of peripheral arthritis , higher patient 's global assessment of disease activity , and lower modified Schober test . In August 2010 , 64 % of patients were still using their TNF-α blocking agent with a median follow-up of 33.1 months ( range 2.4 to 68.2 ) . Baseline predictors of discontinuation of TNF-α blocking therapy were female gender , absence of peripheral arthritis , higher BASDAI , lower ESR level , and lower CRP level . Conclusions Besides younger age and male gender , objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and /or continuation of TNF-α blocking therapy . In contrast , higher baseline BASDAI score was independently associated with treatment discontinuation . Based on these results , it seems clinical ly relevant to include more objective variables in the evaluation of anti-TNF-α treatment BACKGROUND Etanercept , a tumour-necrosis-factor inhibitor , has shown efficacy in the treatment of rheumatoid arthritis . Psoriatic arthritis and psoriasis are disease states in which tumour necrosis factor , a proinflammatory cytokine , is present in increased concentrations in joints and in the skin . Therefore , psoriatic arthritis and psoriasis may be appropriate therapeutic targets for etanercept . METHODS This r and omised , double-blind , placebo-controlled , 12 week study assessed the efficacy and safety of etanercept ( 25 mg twice-weekly subcutaneous injections ) or placebo in 60 patients with psoriatic arthritis and psoriasis . Psoriatic arthritis endpoints included the proportion of patients who met the Psoriatic Arthritis Response Criteria ( PsARC ) and who met the American College of Rheumatology preliminary criteria for improvement ( ACR20 ) . Psoriasis endpoints included improvement in the psoriasis area and severity index ( PASI ) and improvement in prospect ively-identified individual target lesions . FINDINGS In this 12 week study , 26 ( 87 % ) of etanercept-treated patients met the PsARC , compared with seven ( 23 % ) of placebo-controlled patients . The ARC20 was achieved by 22 ( 73 % ) of etanercept-treated patients compared with four ( 13 % ) of placebo-treated patients . Of the 19 patients in each treatment group who could be assessed for psoriasis ( > or = 3 % body surface area ) , five ( 26 % ) of etanercept-treated patients achieved a 75 % improvement in the PASI , compared with none of the placebo-treated patients ( p=0.015 ) . The median PASI improvement was 46 % in etanercept-treated patients versus 9 % in placebo-treated patients ; similarly , median target lesion improvements were 50 % and 0 , respectively . Etanercept was well tolerated . INTERPRETATION Etanercept offers patients with psoriatic arthritis and psoriasis a new therapeutic option for control of their disease Objectives : To determine the predictive factors of clinical response to infliximab in patients with refractory psoriatic polyarthritis . Methods : A multicentre open study which included 69 patients with psoriatic polyarthritis refractory to methotrexate ( 15 mg/week at least for 8 weeks ) . Patients were treated with infliximab 5 mg/kg every 8 weeks in addition to their stable doses of methotrexate . A major clinical response was defined by the ACR50 at week 38 . Logistic regression analysis was performed to analyse which of the following measures at the start of treatment were associated with an ACR50 response : demographic and clinical characteristics , duration of disease , tender and swollen joint counts , involvement of large joints ( knee or hip , or both ) , erythrocyte sedimentation rate , C reactive protein ( CRP ) , Health Assessment Question naire disability index , axial involvement , and the presence of erosions at baseline . Results : In an intention to treat analysis 30/69 ( 44 % ) patients achieved an ACR50 response . In the univariate analysis both the presence of large joint involvement and severe disability were associated with a poor clinical response . In a multivariate logistic regression analysis high CRP values were independently associated with a good therapeutic response ( odds ratio ( OR ) = 18.7 ; 95 % confidence interval ( CI ) 1.8 to 181.6 ; p = 0.011 ) . In contrast , large joint involvement and severe disability were associated with a poor response , which reached significance for large joint involvement ( OR = 29.3 ; 95 % CI 3.2 to 266.3 ; p = 0.003 ) . Conclusion : A lower disability and , in particular , the absence of large joint involvement and higher CRP serum levels at the start of infliximab treatment are factors that seem to influence the probability of achieving a good therapeutic response in patients with psoriatic arthritis OBJECTIVE Adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody , was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis ( PsA ) . METHODS Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were r and omized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks . Study visits were at baseline , weeks 2 and 4 , and every 4 weeks thereafter . The primary efficacy end points were the American College of Rheumatology 20 % improvement ( ACR20 ) response at week 12 and the change in the modified total Sharp score of structural damage at week 24 . Secondary end points were measures of joint disease , disability , and quality of life in all patients , as well as the severity of skin disease in those patients with psoriasis involving at least 3 % of body surface area . RESULTS At week 12 , 58 % of the adalimumab-treated patients ( 87 of 151 ) achieved an ACR20 response , compared with 14 % of the placebo-treated patients ( 23 of 162 ) ( P < 0.001 ) . At week 24 , similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo ( P < 0.001 ) . Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index ( PASI ) , 59 % achieved a 75 % PASI improvement response at 24 weeks , compared with 1 % of the 69 placebo-treated patients evaluated ( P < 0.001 ) . Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo . Adalimumab was generally safe and well-tolerated . CONCLUSION Adalimumab significantly improved joint and skin manifestations , inhibited structural changes on radiographs , lessened disability due to joint damage , and improved quality of life in patients with moderately to severely active OBJECTIVE To examine the baseline demographic and disease characteristics that might influence improvement as measured by the Assessment in Ankylosing Spondylitis Response Criteria ( ASAS 20 ) in patients with ankylosing spondylitis ( AS ) . METHODS A multicenter Phase 3 study was performed to compare the safety and efficacy of 24 weeks of etanercept 25 mg subcutaneous injection twice weekly ( n = 138 ) and placebo  ( n = 139 ) in patients with AS . The ASAS 20 was measured at multiple time points . Using a significance level of 0.05 , a repeated measures logistic regression model was used to determine which baseline factors influenced response in the etanercept-treated patients during the 24-week double blind portion of the trial . The following baseline factors were used in the model : demographic and disease severity variables , concomitant medications , extra-articular manifestations , and HLA-B27 status . The predictive capability of the model was then tested on the patients receiving placebo after they had received open-label etanercept treatment . RESULTS Baseline factors that were significant predictors of an ASAS 20 response in etanercept-treated patients were C-reactive protein ( CRP ) , back pain score , and Bath Ankylosing Spondylitis Functional Index ( BASFI ) score . Although clinical response to etanercept was seen at all levels of baseline disease activity , responses were consistently more likely with higher CRP levels or back pain scores and less likely with increased BASFI scores at baseline . CONCLUSIONS Higher CRP values and back pain scores and lower BASFI scores at baseline were significant predictors of a higher ASAS 20 response in patients with AS receiving etanercept but predictive value was of insufficient magnitude to determine treatment in individual patients Introduction The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences . The aim of this study was to determine whether body mass index ( BMI ) affects response to infliximab ( IFX ) in ankylosing spondylitis ( AS ) patients . Methods In 155 patients retrospectively included with active AS , the  BMI  was calculated before initiation of IFX treatment ( 5 mg/kg intravenously ) . After 6 months of treatment , changes from baseline in BASDAI , Visual Analogue Scale ( VAS ) pain , C-reactive protein ( CRP ) level , and total dose of nonsteroidal antiinflammatory drug ( NSAID  ) were dichotomized with a threshold corresponding to a decrease of 50 % of initial level of the measure , into binary variables assessing response to IFX ( BASDAI50 , VAS50 , CRP50 , NSAID50 ) . Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression . Results Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 ( P = 0.0003 ; OR , 0.87 ; 95 % CI ( 0.81 to 0.94 ) ) , VAS50 ( P < 0.0001 ; OR , 0.87 ; 95 % CI ( 0.80 to 0.93 ) ) ; CRP50 ( P = 0.0279 ; OR , 0.93 ; 95 % CI ( 0.88 to 0.99 ) ) , and NSAID50 ( P = 0.0077 ; OR , 0.91 ; 95 % CI ( 0.85 to 0.97 ) ) , criteria . According to the three WHO BMI categories , similar results were found for BASDAI50 ( 77.6 % , 48.9 % , and 26.5 % ; P < 0.0001 ) , VAS50 ( 72.6 % , 40.4 % , and 16.7 % ; P < 0.0001 ) ; CRP50 ( 87.5 % , 65.7 % , and 38.5 % ; P = 0.0001 ) , and NSAID50 ( 63.2 % , 51.5 % , and 34.6 % ; P = 0.06 ) . Conclusions This study provides the first evidence that a high BMI negatively influences the response to IFX in AS . Further prospect i ve studies , including assessment of the fat mass , pharmacokinetics , and adipokines dosages are m and atory to eluci date the role of obesity in AS IFX response Introduction To identify independent predictors of radiographic progression in psoriatic arthritis ( PsA ) for patients treated with adalimumab or placebo in the Adalimumab Effectiveness in PsA Trial ( ADEPT ) . Methods Univariate analyses and multivariate linear regression analyses assessed risk for radiographic progression ( change in modified total Sharp score , ΔmTSS > 0.5 ) from baseline to week 24 for C-reactive protein ( CRP ) and other baseline variables , and for 24-week time-averaged CRP ( univariate analysis only ) . Subanalyses determined mean ΔmTSS for CRP subgroups . Analyses were post hoc , with observed data . Results One hundred and forty-four adalimumab-treated patients and 152 placebo-treated patients were assessed . Mean CRP was 64 % lower by week 2 with adalimumab and essentially unchanged with placebo . Univariate analyses indicated that elevated CRP at baseline and time-averaged CRP were strongly associated with radiographic progression  for placebo-treated patients but not for adalimumab-treated patients . Multivariate analysis confirmed that elevated baseline CRP was the only strong independent risk factor for radiographic progression ( for CRP ≥1.0 mg/dl : odds ratio = 3.28 , 95 % confidence interval = 1.66 to 6.51 , P < 0.001 ) . Adalimumab treatment reduced risk of progression approximately fivefold . The difference between mean ΔmTSS  for adalimumab versus placebo was greatest for patients with baseline CRP ≥2.0 mg/dl ( -0.5 vs. 2.6 ) . Conclusions Systemic inflammation in PsA , as indicated by elevated baseline CRP , was the only strong independent predictor of radiographic progression . This association was observed predominantly for placebo-treated patients . Adalimumab treatment substantially reduced the overall risk of radiographic progression , and provided greatest radiographic benefit for patients with the greatest CRP concentrations at baseline . Trial Registration Trial registration : NCT00195689 Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-axSpA ( NCT01087762 ) , an ongoing Phase 3 trial in patients with axial spondyloarthritis ( axSpA ) , including patients with ankylosing spondylitis ( AS ) and non-radiographic axSpA ( nr-axSpA ) . Methods Patients with active axSpA were r and omised 1:1:1 to placebo , CZP 200 mg every 2 weeks  ( Q2W ) or  CZP 400 mg every 4 weeks ( Q4W ) . In total 325 patients were r and omised . Primary endpoint was ASAS20 ( Assessment of SpondyloArthritis international Society 20 ) response at week 12 . Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , and Bath Ankylosing Spondylitis Metrology Index ( BASMI ) linear . Results Baseline disease activity was similar between AS and nr-axSpA. At week 12 , ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo ( 57.7 and 63.6 vs 38.3 , p≤0.004 ) . At week 24 , combined CZP arms showed significant ( p<0.001 ) differences in change from baseline versus placebo in BASFI ( −2.28 vs −0.40 ) , BASDAI ( −3.05 vs −1.05 ) , and BASMI ( −0.52 vs −0.07 ) . Improvements were observed as early as week 1 . Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA sub population s. Adverse events were reported in 70.4 % vs 62.6 % , and serious adverse events in 4.7 % vs 4.7 % of All CZP versus  placebo groups . No deaths or malignancies were reported . Conclusions CZP rapidly reduced the signs and symptoms of axSpA , with no new safety signals observed compared to the safety profile of CZP in RA . Similar improvements were observed across CZP dosing regimens , and in AS and nr-axSpA patients UNLABELLED BACKGROUND Treatment options for patients with ankylosing spondylitis are few . We aim ed to assess the effectiveness of infliximab , an antibody to tumour necrosis factor (TNF)-alpha , in treatment of such patients . METHODS In this 12-week placebo-controlled multicentre study , we r and omly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab ( 5 mg/kg ) and 35 to placebo at weeks 0 , 2 , and 6 . One patient in the infliximab group was withdrawn from the study . Our primary outcome was regression of disease activity of at least 50 % . To assess response , we used vali date d clinical criteria from the ankylosing spondylitis assessment working group , including disease activity ( BASDAI ) , functional indices ( BASFI ) , metrology ( BASMI ) , and quality of life ( short form 36 ) . Analyses were done by intention to treat . FINDINGS 18 ( 53 % ) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50 % compared with three ( 9 % ) of 35 on placebo ( difference 44 % [ 95 % CI 23 - 61 ] , p<0.0001 ) . Function and quality of life also improved significantly on infliximab but not on placebo ( p<0.0001 and p<0.0001 , respectively ) . Treatment with infliximab was generally well tolerated , but three patients had to stop treatment because of systemic tuberculosis , allergic granulomatosis of the lung , or mild leucopenia . INTERPRETATION Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis . Since there are some potentially serious adverse effects , we recommend that this treatment mainly be used in co-operation with rheumatological centres The objective of this study was to evaluate if there are early clinical parameters in AS patients treated with three st and ard infusions of infliximab  , which would predict whether a patient will derive a significant improvement at the tenth week , or whether there will be a lengthy clinical response after discontinuing the infusions . Sixty three AS patients were given three infusions of 5 mg/kg of infliximab at weeks 0 , 2 , and 6 and evaluated serially before each infusion and also at week 10 . Afterwards , patients were followed up by telephone interview until their disease activities were > 60 % of the baseline values . At that point , disease was considered to have relapsed . Clinical parameters at baseline as well as at week 2 were used for analysis to identify factors that might predict an improvement at week 10 , or predict a delayed relapse . A predictor is regarded as being useful if the area under the curve ( AUC ) when analyzed by receiver operator calculations ( ROC ) exceeds 0.75 . No parameters at baseline have sufficient predictive values . However , ASAS20 ( Assessment in Ankylosing Spondylitis International Working Group criteria ) at week 2 predicts improvement at week 10 , and also duration of clinical response after discontinuing the infliximab at week 6 . The response to one pulse of  infliximab  is the best predictor of subsequent response as well as rate of relapse after discontinuing the infliximab OBJECTIVES The aims of this study were to assess the efficacy of infliximab ( IFX ) combined with methotrexate ( MTX ) versus IFX alone in the treatment of ankylosing spondylitis ( AS ) . METHODS The study was a 30weeks open label and prospect i ve study of parallel groups in 19 patients with active AS . These patients had shown incomplete therapeutic response to st and ard therapy ( full dose of non-steroidal anti-inflammatory drugs : NSAIDs ) and disease modifying antirheumatic drugs : DMARDs ( MTX or sulfasalazine : SLZ ) for a period of at least 12 weeks and were treated with IFX ( 5mg/kg ) . Patients were divided into two treatment groups according to the previous treatment : in Group A , 9 patients previously treated with 7.5mg/week of MTX  were treated with IFX in addition to MTX ( IFX+MTX ) ; in Group B , 10 patients previously treated only with NSAIDs  were treated with IFX ( 5mg/kg ) as monotherapy ( IFX ) . The primary outcome was improvement in disease activity shown by the BASDAI50 at week 30 ; the secondary outcome included comparison of the proportions of subjects in each group achieving response criteria proposed by the ASAS group . BASDAI , BASFI , ESR , CRP , pain , inflammation and Patient Global Assessment were also recorded . RESULTS Both groups were similar in sex ratio , clinical forms and B27 . Differences between groups occurred only in the disease duration and age of the patient . At 14 and 30 weeks only 50 % and 10 % respectively of the patients from the IFX group achieved BASDAI50 response compared to 89 % of patients from the IFX+MTX group . The difference between groups at 30 weeks was statistically significant ( p=0.001 ; percentage of difference : 79 % ; 95 % confidence interval ( CI ) : 26 - 93 % : ) . ASAS50 was reached in 67 % and 55.6 % of patients from the IFX+MTX group at 14 and 30 weeks respectively , compared with 30 % and 0 % of patients from the IFX group The difference between groups at 30 weeks was statistically significant ( p=0.011 ; percentage of difference : 57 % ; 95 % CI : 8 - 84.7 % ) . CONCLUSION Infliximab in combination with MTX seems to increase the efficacy of the therapeutic response in active AS patients , but more wide-ranging studies are necessary , mainly long-term studies OBJECTIVE To determine predictors and time to response to treatment with TNF-alpha blockers in patients with PsA in a longitudinal observational cohort . METHODS We performed a cohort analysis of patients who were followed prospect ively in a large PsA clinic . Response to treatment was defined as an improvement of at least 40 % in active ( tender and /or swollen ) and swollen joint count ( SJC ) and 50 % improvement in the Psoriasis Area and Severity Index ( PASI ) score . RESULTS Ninety-five patients were included in the analysis . Of the total patients , 72.6 and 77.9 % demonstrated 40 % improvement in active joint counts at 3 and 12 months , respectively . Also , 80.5 and 87.4 % of the patients showed 40 % improvement in SJC at 3 and 12 months , respectively . A PASI50 was achieved by 54 and 60.4 % after 3 and 12 months of treatment , respectively . Of 17 patients who did not achieve 40 % improvement in total SJC at 3 months , 11 ( 64.7 % ) responded at 12 months . In multivariate analysis , the number of swollen joints at baseline predicted response of total active joints at 12 months [ odds ratio ( OR ) 1.34 ; P = 0.02 ] , whereas past use of TNF-alpha blocker decreased odds of response ( OR 0.05 ; P = 0.01 ) . CONCLUSION TNF-alpha blockers are effective in most PsA patients with the majority responding within 3 months of treatment . A significant proportion of the early non-responders will have a delayed response to treatment . Higher SJC at baseline and no prior use of TNF-alpha blockers predict response Objectives : There is evidence that fat tissue may influence the response to therapy in patients with arthritis . The aim of this study was to assess whether the body mass index ( BMI ) affects rates of clinical remission in patients with psoriatic arthritis ( PsA ) treated with anti-tumour necrosis factor (TNF)-α biological drugs . Method : We retrospectively studied 135 patients with active peripheral PsA ( 45 obese , 47 overweight , and 43 normal-weight ) . Baseline BMI was correlated with the clinical response to adalimumab , etanercept , or infliximab . After 36 months ( median , range 6–79 ) of treatment , disease remission rates were assessed using the Disease Activity Score in 28 joints ( DAS28 ) or the Simplified Disease Activity Index ( SDAI ) . Possible predictors of clinical outcomes were assessed by multivariate analysis . Results : At baseline , BMI was significantly correlated only with the Health Assessment Question naire ( HAQ ) score ( r = 0.21 , p = 0.02 ) and not with disease activity . BMI did not predict disease remission or changes in HAQ score  following anti-TNF-α therapy . Obese patients showed a significantly higher HAQ score and took significantly lower doses of prednisone than normal-weight or overweight patients , but their disease remission rates on the DAS28 ( 37 % ) or the SDAI ( 21 % ) were not significantly different from those of the other two groups ( 44 % and 21 % , respectively ) , regardless of the TNF-α inhibitor prescribed . Conclusions : In our retrospective analysis , disease activity and clinical response  to anti-TNF-α therapy in PsA do not seem to be affected by BMI . Further prospect i ve studies are needed to confirm these preliminary results OBJECTIVES To compare the clinical manifestations of spinal disease , peripheral arthritis and enthesitis , and to evaluate the effectiveness of adalimumab in a large cohort of patients with AS in relation to the presence or absence of psoriasis . METHODS Patients aged > or = 18 years with active AS were enrolled in an open-label study of adalimumab 40 mg every other week . Clinical symptoms were measured at baseline and Week 12 using st and ard assessment criteria . Differences between patients with and those without psoriasis were assessed . The relationship between changes in skin and AS symptoms was also analysed . RESULTS Of 1250 patients with AS who were enrolled in the study , 148 ( 11.8 % ) had a history of psoriasis , including 108 patients with current ( active ) psoriasis at entry . Baseline disease characteristics , including spinal structural damage , peripheral arthritis ( > or = 1 swollen joints ) and enthesitis ( > or = 1 inflamed entheses ) , were similar in both groups . At Week 12 , Assessment of SpondyloArthritis international Society 40 % response was achieved by 46.7 and 54.7 % and Bath AS Disease Activity Index 50 % response by 58.6 and 57.0 % of patients with and without psoriasis , respectively . Median changes in swollen joint scores and Maastricht AS Enthesitis Scores were similar in both groups . Skin changes during adalimumab treatment in AS patients with a history of psoriasis did not correlate with changes in AS symptoms . CONCLUSIONS The presence of psoriasis had no influence on the other clinical manifestations of patients with AS . Treatment with adalimumab markedly improved axial disease , peripheral arthritis and enthesitis , regardless of history of psoriasis OBJECTIVE To evaluate the role of MRI in predicting a Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) improvement of at least 50 % ( BASDAI 50 ) upon anti-tumour necrosis factor ( TNF ) therapy of active ankylosing spondylitis ( AS ) . METHODS  MRIs from patients with active AS who participated in r and omised controlled trials were analysed with respect to presence and extent of active inflammatory lesions as detected in the spine ( n = 46 ) , sacroiliac ( SI ) joints ( n = 42 ) and both sites ( n = 26 ) . Univariate and multivariate logistic regression analyses were applied to evaluate MRI and clinical data in predicting a BASDAI 50 response . RESULTS The Berlin MRI spine score ( odds ratio ( OR ) 1.16 , 95 % CI 1.02 to 1.33 ) and disease duration ( OR 0.9 , 95 % CI 0.63 to 0.97 ) were statistically significant predictors of a BASDAI 50 response using regression analysis while there was only a trend for C-reactive protein ( CRP ) . The likelihood ratio ( LR ) for achievement of BASDAI 50 was increased in patients with a Berlin MRI spine score > /=11 ( LR 6.7 ) , disease duration < 10 years ( LR 4.2 ) and CRP > /=40 mg/litre ( LR 3.4 ) . All patients with two or three of these predictors improved clinical ly ( as assessed by BASDAI ) by at least 45 % . Disease duration > 20 years , normal CRP and no active inflammatory lesion in the spine were highly predictive of not achieving BASDAI 50 . A trend was only found for the MRI score of SI joints to be predictive . CONCLUSIONS Widespread inflammation in the spine as detected by MRI contributes to predicting a BASDAI 50 response in active patients with AS treated with anti-TNF agents OBJECTIVE To evaluate the efficacy and safety of golimumab in patients with ankylosing spondylitis ( AS ) in the GO-RAISE study . METHODS Patients with active AS , a Bath AS Disease Activity Index ( BASDAI ) score > or = 4 , and a back pain score of > or = 4 were r and omly assigned in a 1.8:1.8:1 ratio to receive subcutaneous injections of golimumab ( 50 mg or 100 mg ) or placebo every 4 weeks . The primary end point was the proportion of patients with at least 20 % improvement in the ASsessment in AS ( ASAS20 ) criteria at week 14 . RESULTS At r and omization , 138 , 140 , and 78 patients were assigned to the 50-mg , 100-mg , and placebo groups , respectively . After 14 weeks , 59.4 % , 60.0 % , and 21.8 % of patients , respectively , were ASAS20 responders ( P < 0.001 ) . A 40 % improvement in the ASAS criteria at week 24 occurred in 43.5 % , 54.3 % , and 15.4 % of patients , respectively . Patients receiving golimumab also showed significant improvement in the physical and mental component summary scores of the Short Form 36 Health Survey , the Jenkins Sleep Evaluation Question naire score , the BASDAI score , and the Bath AS Functional Index score , but not the Bath AS Metrology Index score . Through week 24 , 85.6 % of golimumab-treated patients and 76.6 % of patients in the placebo group had > or = 1 adverse event , and 5.4 % and 6.5 % of patients , respectively , had > or = 1 serious adverse event . Eight golimumab-treated patients and 1 placebo-treated patient had markedly abnormal liver enzyme values ( > or = 100 % increase from baseline and a value > 150 IU/liter ) , which were transient . CONCLUSION Golimumab was effective and well tolerated in a large cohort of patients with AS during a 24-week study period BACKGROUND TNFalpha blockers have been shown to be highly efficacious in patients with active ankylosing spondylitis ( AS ) . OBJECTIVE To identify parameters predicting the clinical response to TNF blockers in AS . METHODS Patients with active AS participated in two placebo controlled , r and omised trials conducted in Germany with infliximab ( n = 69 ) and etanercept ( n = 30 ) , respectively . For inclusion in either trial patients had to have high disease activity ( BASDAI > or=4 ) and a spinal pain score ( numerical rating scale 0 - 10 ) > or=4 despite treatment with NSAIDs . A major clinical response was defined as a 50 % improvement of the initial BASDAI ( BASDAI 50 ) after 12 weeks ' treatment with active drug . Logistic regression likelihood ratio tests ( univariate and multivariate ) , Student 's t test , and chi(2 ) tests were performed . RESULTS Univariate analysis showed the following to be predictors of a major response ( BASDAI 50 ) to treatment : shorter disease duration ( p = 0.003 ) ; lower BASFI ( p = 0.007 ) ; younger age ( p = 0.009 ) ; raised ESR ( p = 0.033 ) ; raised CRP ( p = 0.035 ) . After adjustment for disease duration , BASFI , ESR , and CRP , but not age , remained significantly associated . After adjustment for disease duration and for BASFI , ESR , CRP , and in addition , a higher BASDAI were significantly associated with response . The best multivariate model built by stepwise regression contained the covariables disease duration , BASFI , BASDAI , and CRP . CONCLUSION A shorter disease duration , younger age , and a lower BASFI are predictors of a major clinical response to TNF blockers in active AS . Raised CRP and a higher BASDAI may also be valuable predictors . These data need to be confirmed in further studies Objective . We evaluated the effectiveness and safety of adalimumab in a large cohort of patients with active ankylosing spondylitis ( AS ) and identified clinical predictors of good clinical response . Methods . Patients with active AS [ Bath AS Disease Activity Index ( BASDAI ) ≥4 ] received adalimumab 40 mg every other week in addition to their st and ard antirheumatic therapies in a multinational 12-week , open-label study . We used 3 definitions of good clinical response : 50 % improvement in the BASDAI ( BASDAI = 50 ) , 40 % improvement in the ASsessment s of SpondyloArthritis International Society criteria ( ASAS40 ) , or ASAS partial remission . Response predictors were determined by logistic regression with backward elimination ( selection level 5 % ) . Results . Of 1250 patients , 1159 ( 92.7 % ) completed 12 weeks of adalimumab treatment . At Week 12 , 57.2 % of patients achieved BASDAI 50 , 53.7 % achieved ASAS40 , and 27.7 % achieved ASAS partial remission . Important predictors of good clinical response ( BASDAI 50 , ASAS40 , and partial remission ) were younger age ( p < 0.001 ) , and greater C-reactive protein ( CRP ) concentration ( p ≤ 0.001 ) , HLA-B27 positivity ( p ≤ 0.01 ) , and tumor necrosis factor ( TNF ) antagonist naivety ( p < 0.001 ) . Conclusion . Adalimumab was effective in this large cohort of patients with AS , with more than half of patients achieving a BASDAI 50 or ASAS40 response and more than a quarter of patients reaching partial remission at Week 12.Younger age , greater CRP concentrations , HLA-B27 positivity , and TNF antagonist naivety were strongly associated with BASDAI 50 , ASAS40 , and partial remission responses . Clinical Trials.gov identifier : NCT00478660 OBJECTIVE To evaluate the efficacy and safety of apremilast , a novel , orally available small molecule that specifically targets phosphodiesterase 4 , in the treatment of active psoriatic arthritis ( PsA ) . METHODS This phase II , multicenter , r and omized , double-blind , placebo-controlled study included the following : a 12-week treatment phase , with patients receiving placebo , apremilast 20 mg twice per day , or apremilast 40 mg once per day ; a 12-week treatment-extension phase , with patients in the placebo group re-r and omized to receive apremilast ; and a 4-week observational phase after treatment cessation . The primary end point was the proportion of patients achieving the American College of Rheumatology criteria for 20 % improvement ( ACR20 ) at week 12 . Safety assessment s included adverse events ( AEs ) , physical examinations , vital signs , laboratory parameters , and electrocardiograms . RESULTS Of the 204 patients with PsA who were r and omized to a treatment group , 165 completed the treatment phase . At the end of the treatment phase ( week 12 ) , 43.5 % of patients receiving apremilast 20 mg twice per day ( P < 0.001 ) and 35.8 % of those receiving 40 mg once per day ( P = 0.002 ) achieved an ACR20 response , compared with 11.8 % of those receiving placebo . At the end of the treatment-extension phase ( week 24 ) , > 40 % of patients in each group ( patients receiving apremilast 20 mg twice per day , patients receiving apremilast 40 mg once per day , and patients in the placebo group re-r and omized to receive apremilast ) achieved the ACR20 level of improvement . Most patients in the treatment phase ( 84.3 % ) and treatment-extension phase ( 68.3 % ) reported ≥ 1 AE . Diarrhea , headache , nausea , fatigue , and nasopharyngitis were reported most frequently ; most events were mild or moderate . No clinical ly relevant laboratory or electrocardiographic abnormalities were reported . CONCLUSION Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. The balance of efficacy , tolerability , and safety supports further study of apremilast in OBJECTIVE To evaluate the efficacy and safety of the tumor necrosis factor ( TNF ) antagonist adalimumab in patients with axial spondylarthritis ( SpA ) without radiographically defined sacroiliitis refractory to conventional treatment . METHODS Patients with active axial SpA ( n = 46 ) were r and omized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks , followed by an open-label extension that continued up to week 52 . The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria , including 2 of the following 3 criteria : inflammatory back pain , HLA-B27 positivity , or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging , in the absence of radiographic evidence of sacroiliitis . The primary end point was a 40 % response according to the improvement criteria of the Assessment of SpondyloArthritis international Society ( ASAS40 ) . RESULTS All 46 patients ( 22 receiving adalimumab and 24 receiving placebo ) completed the 12-week trial ; 38 patients completed the extension period to week 52 . At week 12 , an ASAS40 response was achieved by 54.5 % of the adalimumab-treated patients , as compared with 12.5 % of the placebo-treated patients ( P = 0.004 ) . After switching to adalimumab , a similar degree of efficacy was also achieved by the patients who were initially treated with placebo . Efficacy was maintained in all patients until week 52 . Young age at study entry and an elevated C-reactive protein concentration were the best predictors of achieving an ASAS40 response . Serious adverse events occurred in 5 patients , none of which was related to the study drug . CONCLUSION Adalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis Background : The use of tumour necrosis factor ( TNF ) blocking agents in psoriatic arthritis ( PsA ) is increasing , and the SSATG register has followed patients with PsA for more than 5 years . The aim of the present work therefore was to present efficacy and tolerability data of TNF-blocking agents on PsA in clinical practice , and to study potential predictors for drug survival ( the length of time a patient continues to take a particular drug ) . Material s and methods : Patients ( n = 261 ) with active PsA , starting anti-TNF therapy for the first time in southern Sweden , were included . Basal characteristics , disease activity measures , and termination reason for blockers were prospect ively collected during the period April 1999 to September 2006 . Cox proportional hazard models were used to investigate predictors for treatment termination . Results : Overall , response rates at 3–12 months for global visual analogue scale ( VASglobal50 ) and pain VAS ( VASpain50 ) were about 50 % , whereas response rates for European League Against Rheumatism ( EULAR ) scoring “ overall ” and EULAR “ good ” were around 75 % and 55 % , respectively . Concomitant methotrexate ( MTX ) ( hazard ratio ( HR ) 0.64 , 95 % CI 0.39–0.95 , p = 0.03 ) , etanercept ( HR 0.49 , 95 % CI 0.28–0.86 , p = 0.01 ) , and high C-reactive protein ( CRP ) levels ( HR 0.77 , 95 % CI 0.61–0.97 , p = 0.03 ) at treatment initiation were associated with better overall drug survival . The improved drug survival of concomitant MTX appeared to be related to significantly fewer dropouts because of adverse events ( HR = 0.24 ( 0.11–0.52 ) , p<0.01 ) . The blockers were well tolerated with a rate of serious adverse events of 5–6 % per year . No unexpected serious adverse events were observed . Conclusion : Concomitant MTX and high CRP levels are associated with treatment continuation of anti-TNF therapy in patients with PsA regardless of joint distribution . The positive effect of MTX was primarily linked to fewer dropouts because of adverse events Objective . To investigate whether level of serum matrix metalloproteinase-3 ( MMP-3 ) can serve as a biomarker for monitoring and predicting response to etanercept treatment in patients with ankylosing spondylitis ( AS ) in daily clinical practice . Methods . Ninety-two consecutive AS out patients with active disease who started etanercept treatment were included in this longitudinal observational study . Clinical data were collected prospect ively at baseline and after 3 and 12 months of treatment . At the same timepoints , serum MMP-3 levels were measured retrospectively by ELISA . Results . Since baseline serum MMP-3 levels were significantly higher in male compared to female patients with AS , data analysis was split for gender . Changes in serum MMP-3 levels after etanercept treatment correlated positively with changes in clinical assessment s of disease activity and physical function in both male and female patients . Receiver operating characteristic analysis in male patients showed that baseline serum MMP-3 levels had poor accuracy ( AUC < 0.7 ) to discriminate between Assessment s in Ankylosing Spondylitis 20 ( ASAS20 ) or ASAS40 responders and nonresponders after 3 or 12 months of treatment . The accuracy of change in serum MMP-3 levels from baseline to 3 months in predicting response after 3 or 12 months of treatment was poor for ASAS40 ( AUC < 0.7 ) or moderate for ASAS20 ( AUC = 0.752 and 0.744 , respectively ) , and was not superior to the accuracy of change in the currently used objective biomarkers , erythrocyte sedimentation rate and C-reactive protein . Conclusion . Although significant changes in serum MMP-3 levels were found after etanercept treatment , data analysis indicates that serum MMP-3 levels are not very useful for monitoring and predicting response to etanercept treatment in patients with AS in daily clinical practice Objectives To use prospect ively registered data from the Danish nationwide rheumatological data base ( DANBIO ) to describe disease activity , clinical response , treatment duration and predictors of drug survival ( ie , number of days individual patients maintained treatment ) and clinical response among patients with ankylosing spondylitis ( AS ) receiving their first treatment series with a tumour necrosis factor α ( TNFα ) inhibitor .  Methods 842 TNFα inhibitor naive patients with AS were identified in DANBIO .  Clinical response , drug survival and predictors thereof were investigated . ‘ Clinical response ’ was defined as a 50 % or 20 mm reduction in Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) within 6 months compared with baseline . Achievement of a BASDAI < 40 mm within 6 months was used as a second response parameter . Results 603 patients ( 72 % ) were men , disease duration 5 ( 1–13 ) years ( median ( IQR ) , age 41 ( 32–50 ) years . 445 ( 53 % ) received infliximab , 247 ( 29 % ) adalimumab and 150 ( 18 % ) etanercept . Parameters at baseline/1-year follow-up were : C-reactive protein ( CRP ) : 14 (7–27)/5 ( 2–10 ) mg/l , BASDAI 59 (44–72)/21 ( 8–39 ) mm , Bath Ankylosing Spondylitis Functional Index ( BASFI ) 50 (34–67)/24 ( 9–45 ) mm , Bath Ankylosing Spondylitis Metrology Index 40 (20–50)/20 ( 10–40 ) mm . Within 6 months , 407/644 patients ( 63 % ) achieved a clinical response . Median drug survival was 4.3 years . One- and 2-year survival rates were 74 % and 63 % , respectively . Baseline characteristics associated with longer drug survival were male gender , CRP > 14 mg/l and low visual analogue scale fatigue ( Cox regression analysis ) . Age , TNFα inhibitor and methotrexate use were insignificant . CRP > 14 mg/l , lower BASFI and younger age at baseline was associated with clinical response and achievement of a BASDAI < 40 mm ( logistic regression analysis ) . Conclusion TNFα inhibitors provide a rapid and sustained decrease of disease activity among patients with AS in clinical practice . Factors associated with continued treatment , clinical response and achievement of a BASDAI < 40 mm were identified Objectives To investigate the relation between ankylosing spondylitis disease activity score ( ASDAS ) , Bath ankylosing spondylitis disease activity index ( BASDAI ) and treatment response and biomarkers of inflammation ( C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , YKL-40 ) , angiogenesis ( vascular endothelial growth factor ( VEGF ) ) , cartilage ( C-terminal crosslinking telopeptide of type II collagen ( CTX-II ) , matrix metalloproteinase-3 ( MMP-3 ) , total aggrecan , cartilage oligomeric matrix protein ) and bone ( C-terminal crosslinking telopeptide of type I collagen , osteocalcin ) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha ( TNFα ) inhibitor therapy . Methods ASDAS ( CRP-based ) , BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy . Results Very high ASDAS were associated with high levels of inflammatory biomarkers , while high BASDAI were not related to any biomarkers . Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6 , VEGF , MMP-3 and osteocalcin and between BASDAI and CRP , IL-6 and VEGF . Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation , angiogenesis , MMP-3 and increases in aggrecan and osteocalcin . BASDAI response was associated with larger decreases in CRP and IL-6 . Biomarkers with moderate/high differences in responsiveness for major versus no/ clinical ly important improvement in ASDAS were CRP , IL-6 , VEGF , aggrecan and osteocalcin , and VEGF and CTX-II for BASDAI response versus non-response . Conclusion Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented . Construct validity and responsiveness of IL-6 , VEGF , MMP-3 , total aggrecan and osteocalcin were demonstrated . ASDAS was more associated with these biomarkers than BASDAI , and may better reflect the inflammatory disease processes . Clinical Trials.gov identifier NCT00133315 OBJECTIVE There is increasing evidence that tumor necrosis factor alpha ( TNFalpha ) is central ly involved in the pathogenesis of ankylosing spondylitis ( AS ) and other spondylarthritides . This study was design ed to investigate the efficacy of anti-TNFalpha therapy with etanercept , a 75-kd receptor fusion protein , in active AS . METHODS This multicenter trial had 2 phases : an initial placebo-controlled period of 6 weeks ' duration and an observational phase lasting 24 weeks . Thirty patients with active AS were included . They were r and omized into 2 groups , which received either etanercept ( 25 mg twice weekly ) ( n = 14 ) or placebo ( n = 16 ) for 6 weeks . Then both groups were treated with etanercept . Nonsteroidal antiinflammatory drug ( NSAID ) treatment could be continued , but disease-modifying antirheumatic drugs ( DMARDs ) and steroids had to be withdrawn prior to the study . All patients received etanercept for a total of 12 weeks and were followed up for at least 24 weeks . The Bath AS Disease Activity Index ( BASDAI ) , Bath AS Functional Index , Bath AS Metrology Index , pain level on a numeric rating scale , quality of life by the Short Form 36 , and C-reactive protein ( CRP ) level were assessed . The primary outcome parameter was a > or=50 % improvement in the BASDAI . RESULTS Treatment with etanercept result ed in at least a 50 % regression of disease activity in 57 % of these patients at week 6 , versus 6 % of the placebo-treated patients ( P = 0.004 ) . After the placebo-treated patients switched to etanercept , 56 % improved . The mean + /- SD BASDAI improved from 6.5 + /- 1.2 at baseline to 3.5 + /- 1.9 at week 6 in the etanercept group , with no improvement in the placebo group ( P = 0.003 between groups ) . Similarly , pain , function , mobility , and quality of life improved with etanercept but not with placebo at week 6 ( P < 0.05 ) . Mean CRP levels decreased significantly with etanercept but not with placebo ( P = 0.001 ) . There was ongoing improvement in all parameters in both groups until week 12 and week 18 , respectively ( i.e. , throughout the period of etanercept treatment ) . Disease relapses occurred a mean + /- SD of 6.2 + /- 3.0 weeks after cessation of etanercept . No severe adverse events , including major infections , were observed during the trial . CONCLUSION This study shows that on a short-term basis ( 3 months ) , treatment with etanercept is clearly efficacious in patients with active AS who are receiving NSAID therapy but not DMARDs or steroids .  After cessation of therapy , almost all patients experienced a relapse within a few weeks . Thus , it seems probable that etanercept must be administered continuously in most AS patients to achieve permanent inhibition of the inflammatory process OBJECTIVE To assess the efficacy and safety of golimumab in patients with active psoriatic arthritis ( PsA ) . METHODS Adult patients with PsA who had at least 3 swollen and 3 tender joints and active psoriasis were r and omly assigned to receive subcutaneous injections of placebo  ( n = 113 ) , golimumab 50 mg ( n = 146 ) , or golimumab 100 mg ( n = 146 ) every 4 weeks through week 20 . Efficacy assessment s through week 24 included the American College of Rheumatology 20 % improvement criteria ( ACR20 ) , the Psoriasis Area and Severity Index ( PASI ) in patients in whom at least 3 % of the body surface area was affected by psoriasis at baseline , the  Short Form 36 Health Survey ( SF-36 ) , the disability index of the Health Assessment Question naire ( HAQ ) , the Nail Psoriasis Severity Index ( NAPSI ) , the physician 's global assessment of psoriatic nail disease , and enthesitis ( using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score [ MASES ] index ) . RESULTS At week 14 , 48 % of all patients receiving golimumab , 51 % of patients receiving golimumab 50 mg , and 45 % of patients receiving golimumab 100 mg achieved an ACR20 response ( the primary end point ) , compared with 9 % of patients receiving placebo ( P < 0.001 for all comparisons ) . Among the 74 % of patients in whom at least 3 % of the body surface area was affected by psoriasis at baseline , 40 % of those in the golimumab 50 mg group and 58 % of those in the golimumab 100 mg group had at least 75 % improvement in the PASI at week 14 ( major secondary end point ) , compared with 3 % of placebo-treated patients ( P < 0.001 for both doses ) . Significant improvement was observed for other major secondary end points ( the HAQ and the SF-36 ) , the NAPSI , the physician 's global assessment of psoriatric nail disease , and the PsA-modified MASES index in each golimumab group compared with placebo . This efficacy was maintained through week 24 . Golimumab was generally well tolerated . CONCLUSION Treatment with golimumab at doses of 50 mg and 100 mg significantly improved active PsA and associated skin and nail psoriasis through week 24 Objective . To assess the efficacy and safety of adalimumab or cyclosporine ( CYC ) as monotherapy or combination therapy for patients with active psoriatic arthritis ( PsA ) , despite methotrexate ( MTX ) therapy . Methods . A prospect i ve 12-month , nonr and omized , unblinded clinical trial of 57 , 58 , and 55 patients who received CYC ( 2.5–3.75 mg/kg/day ) , adalimumab ( 40 mg every other week ) , or combination , respectively . Lowering of concomitant nonsteroidal antiinflammatory drugs ( NSAID ) and corticosteroids and reductions of adalimumab and /or CYC doses in responding patients were not restricted . Results . Mean numbers of tender/swollen joints at baseline were 9.7/6.7 in CYC-treated , 13.0/7.8 in adalimumab-treated , and 14.5/9.4 in combination-treated patients , indicating lesser disease severity of patients assigned to the first group . The Psoriatic Arthritis Response Criteria at 12 months were met by 65 % of CYC-treated ( p = 0.0003 in favor of combination treatment ) , 85 % of adalimumab-treated ( p = 0.15 vs combination treatment ) , and 95 % of combination-treated patients , while the American College of Rheumatology-50 response rates were 36 % , 69 % , and 87 % , respectively ( p < 0.0001 and p = 0.03 in favor of combination treatment ) . A significantly greater mean improvement in Health Assessment Question naire Disability Index was achieved by combination treatment ( −1.11 ) vs CYC ( −0.41 ) or adalimumab alone ( −0.85 ) . Combination therapy  significantly improved Psoriasis Area and Severity Index-50 response rates  beyond adalimumab , but not beyond the effect of CYC monotherapy . Doses of NSAID and corticosteroids were reduced in combination-treated patients ; CYC doses and frequency of adalimumab  injections were also reduced in 51 % and 10 % of them , respectively . No new safety signals were observed . Conclusion . The combination of adalimumab and CYC is safe and seemed to produce major improvement in both clinical and serological variables in patients with severely active PsA and inadequate response to MTX OBJECTIVE To evaluate the safety and efficacy of adalimumab , a fully human recombinant IgG1 monoclonal antibody that specifically targets human tumor necrosis factor , in patients with active ankylosing spondylitis ( AS ) . METHODS This was a multicenter , r and omized ( 2:1 ratio ) , double-blind , placebo-controlled study to evaluate a subcutaneous injection of adalimumab , 40 mg every other week , compared with placebo for 24 weeks . The primary efficacy end point was the percentage of patients with a 20 % response according to the ASsessment in Ankylosing Spondylitis International Working Group criteria for improvement ( ASAS20 ) at week 12 . Secondary outcome measures included the ASAS20 at week 24 and multiple measures of disease activity , spinal mobility , and function , as well as ASAS partial remission . RESULTS At week 12 , 58.2 % of adalimumab-treated patients ( 121 of 208 ) achieved an ASAS20 response , compared with 20.6 % of placebo-treated patients ( 22 of 107 ) ( P < 0.001 ) . More patients in the adalimumab group ( 45.2 % [ 94 of 208 ] ) than in the placebo group ( 15.9 % [ 17 of 107 ] ) had at least a 50 % improvement in the Bath Ankylosing Spondylitis Disease Activity Index at week 12 ( P < 0.001 ) . Significant improvements in the ASAS40 response and the response according to the ASAS5/6 criteria at weeks 12 and 24 were also demonstrated ( P < 0.001 ) . Partial remission was achieved by more adalimumab-treated patients than placebo-treated patients ( 22.1 % versus 5.6 % ; P < 0.001 ) . Adalimumab-treated patients reported more adverse events ( 75.0 % versus 59.8 % of placebo-treated patients ; P < 0.05 ) , but there was no statistically significant difference in the incidence of infections . Most adverse events were mild or moderate in severity . CONCLUSION Adalimumab was well-tolerated during the 24-week study period and was associated with a significant and sustained reduction in the signs and symptoms of active AS OBJECTIVE To investigate disease activity , treatment response , and drug survival , and predictors thereof , among Danish patients with psoriatic arthritis ( PsA ) receiving their first treatment series with a tumor necrosis factor α ( TNFα ) inhibitor .  METHODS Patients with PsA were identified from a prospect i ve nationwide rheumatologic data base , the Danish biologics registry DANBIO , using data registered from 2000 - 2009 . Information was obtained on the patients ' clinical response to anti-TNFα treatment ( defined as achievement of the American College of Rheumatology 20 % [ ACR20 ] , ACR50 , and ACR70 improvement criteria or a European League Against Rheumatism [ EULAR ] good response at least once during the first 6 months of treatment ) and duration and rate of drug adherence ( referred to as drug survival ) , as well as predictors thereof . RESULTS Of 764 patients with PsA , 320 received adalimumab , 260 infliximab , and 184 etanercept .  Median drug survival was 2.9 years , and 1-year and 2-year drug survival rates were 70 % and 57 % , respectively . Clinical parameters that showed improvement over 6 months were the C-reactive protein ( CRP ) level , Health Assessment Question naire score , and 28-joint Disease Activity Score . Male sex , CRP level > 10 mg/liter , concomitant methotrexate use , and low patient health visual analog scale score at baseline were associated with longer drug survival . Improvement was achieved by 59 % , 45 % , 24 % , and 54 % of patients according to the ACR20 , ACR50 , ACR70 response criteria and EULAR good response , respectively . A CRP level > 10 mg/liter was predictive of the improvement responses ( odds ratio [ OR ] 2.6 for ACR20 , OR 3.0 for ACR50 , OR 3.6 for ACR70 , and OR 2.2 for EULAR good response ) . CONCLUSION In these patients with PsA treated with their first TNFα inhibitor in clinical practice , high drug adherence and responder rates were observed . Moreover , increased levels of CRP at baseline were associated with both good treatment responses and continued treatment , which may be of clinical value in selecting the patients most likely to benefit from treatment with TNFα inhibitors
OBJECTIVE To identify predictors of response to tumor necrosis factor ( TNF ) antagonists  in ankylosing spondylitis ( AS ) and psoriatic arthritis ( PsA ) .