Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study Comparison of effectiveness and safety of infliximab, etanercept, and adalimumab in psoriatic arthritis patients who experienced an inadequate response to previous disease-modifying antirheumatic drugs Clinical efficacy, radiographic and safety findings through 2 years of golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of the randomised, placebo-controlled GO-REVEAL study The TICOPA protocol (TIght COntrol of Psoriatic Arthritis): a randomised controlled trial to compare intensive management versus standard care in early psoriatic arthritis 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. Factors Associated with Findings of Published Trials of Drug–Drug Comparisons: Why Some Statins Appear More Efficacious than Others Treatment of Psoriatic Arthritis with Tumor Necrosis Factor Inhibitors: Longer-term Outcomes Including Enthesitis and Dactylitis with Golimumab Treatment in the Longterm Extension of a Randomized, Placebo-controlled Study (GO-REVEAL) Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. Severe psoriasis--oral therapy with a new retinoid. Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Patient-Reported Outcomes and the Association With Clinical Response in Patients With Active Psoriatic Arthritis Treated With Golimumab: Findings Through 2 Years of a Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: Results from the induction and maintenance psoriatic arthritis clinical trial 2. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): results of radiographic analyses after 1 year Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Infliximab improves health related quality of life and physical function in patients with psoriatic arthritis Two-year efficacy and safety of infliximab treatment in patients with active psoriatic arthritis: findings of the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT). Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Adalimumab improves joint-related and skin-related functional impairment in patients with psoriatic arthritis: patient-reported outcomes of the Adalimumab Effectiveness in Psoriatic Arthritis Trial Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. 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.
Objective To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis ( PsA ) . Methods In this open-label study , patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy ( N=115 ) were r and omly assigned ( 1:1 ) to receive either infliximab ( 5 mg/kg ) at weeks 0 , 2 , 6 and 14 plus methotrexate ( 15 mg/week ) ; or methotrexate ( 15 mg/week ) alone . The primary assessment was American College of Rheumatology ( ACR ) 20 response at week 16 . Secondary outcome measures included psoriasis area and severity index ( PASI ) , disease activity score in 28 joints ( DAS28 ) and dactylitis and enthesitis assessment s. Results At week 16 , 86.3 % of patients receiving infliximab plus methotrexate and 66.7 % of those receiving methotrexate alone achieved an ACR20 response ( p<0.02 ) . Of patients whose baseline PASI was 2.5 or greater , 97.1 % receiving infliximab plus methotrexate compared with 54.3 % receiving methotrexate alone experienced a 75 % or greater improvement in PASI ( p<0.0001 ) . Improvements in C-reactive protein levels , DAS28 response and remission rates , dactylitis , fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab . In the infliximab plus methotrexate group , 46 % ( 26/57 ) had treatment-related adverse events ( AE ) and two patients had serious AE , compared with 24 % with AE ( 13/54 ) and no serious AE in the methotrexate-alone group . Conclusions Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated . This trial is registered in the US National Institutes of Health clinical trials.gov data base , identifier NCT00367237 The aim of this study is to compare effectiveness and safety of Infliximab ( INF ) , Etanercept ( ETN ) , and Adalimumab ( ADA ) in patients with psoriatic arthritis ( PsA ) with inadequate response to a previous disease-modifying antirheumatic drug ( DMARD ) . One hundred consecutive PsA patients with inadequate response to a previous DMARD entered this study . Clinical and laboratory assessment at baseline ( T0 ) and 12 ( T12 ) months were performed and included physical examination , vital signs , global Psoriasis Area and Severity Index ( PASI ; extension of psoriasis ) , tender joints count ( TJC ) , swollen joint count , health assessment question naire ( HAQ ; question naire for measuring disability ) , and monitoring of adverse events ( AEs ) . After enrolment , all patients were r and omly given INF 5 mg/Kg every 6–8 weeks , ETN 50 mg weekly , or ADA 40 mg every other week . Baseline therapy with DMARD remained unchanged . Effectiveness was defined as percentage of ACR20 responders and as clinical remission and /or minimal disease activity at 12 months treatment . INF , ETN , and ADA all effectively controlled signs and symptoms of PsA. All variables tested showed at T12 for each treatment a significant variation from the baseline value . In particular , patients on INF and ADA showed the greatest improvement in terms of PASI , while patients on ETN showed the greatest improvement on TJC and HAQ . ACR response rates were 72 % of patients on ETN , 70 % of those on ADA , and 75 % of those patients on INF . Occurrence of AEs was reported in 15 % of the cases . Only two AEs in patients on INF were considered drug related , pneumonitis and thrombocytopenia , respectively . All tumor necrosis factor-α blockers significantly controlled signs and symptoms of PsA. An increased knowledge of the different profiles of these agents may help in optimizing their use Objectives To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis ( PsA ) . Methods Adult PsA patients ( ≥3 swollen , ≥3 tender joints , active psoriasis ) were r and omly assigned to subcutaneous injections of placebo , golimumab 50 mg or 100 mg every 4 weeks ( q4wks ) through week 20 . All patients received golimumab 50 or 100 mg beginning week 24 . Findings through 2 years are reported . Efficacy evaluations included ≥20 % improvement in American College of Rheumatology ( ACR20 ) response , good/moderate response in Disease Activity Scores incorporating 28 joints and C-reactive protein ( DAS28-CRP ) , ≥75 % improvement in Psoriasis Area and Severity Index ( PASI75 ) and changes in PsA-modified Sharp/van der Heijde scores ( SHS ) . Results Golimumab treatment through 2 years was effective in maintaining clinical response ( response rates : ACR20 63%–70 % , DAS28-CRP 77%–86 % , PASI75 56%–72 % ) and inhibiting radiographic progression ( mean change in PsA-modified SHS in golimumab-treated patients : −0.36 ) , with no clear difference between doses . No new safety signals were identified through 2 years . With the study 's tuberculosis screening and prophylactic measures , no patient developed active tuberculosis through 2 years . Conclusions Golimumab 50 and 100 mg for up to 2 years yielded sustained clinical and radiographic efficacy when administered to patients with active PsA. Increasing the golimumab dose from 50 to 100 mg q4wks added limited benefit . Golimumab safety through up to 2 years was consistent with other antitumour necrosis factor α agents used to treat PsA. Treatment of patients with latent tuberculosis identified at baseline appeared to be effective in inhibiting the development of active tuberculosis Background Psoriatic Arthritis ( PsA ) is estimated to occur in 10 - 15 % of people with psoriasis and accounts for 13 % of people attending early arthritis clinics . With an increasing awareness of the poor outcomes associated with PsA and the availability of new effective , but costly , treatments , there is an urgent need to research the optimal treatment for patients with PsA. The aim of the TICOPA study is to establish whether , in treatment naive early PsA patients , “ tight control ” intensive management with protocol driven therapies and pre-defined objective targets for treatment can improve clinical outcome compared to st and ard care alone . Methods / design TICOPA is a UK multicentre , open-label , r and omised controlled , parallel group trial of 206 patients with early PsA. Patients will be r and omised on a 1:1 basis to receive either st and ard care ( 12 weekly review ) or intensive management ( 4 weekly review ) for a period of 48 weeks . Patients assigned to the intensive management group will follow a strict treatment protocol whereby dose continuation/escalation is determined through the objective assessment of the minimal disease activity ( MDA ) criteria . Patients assigned to the st and ard care group will have treatment prescribed as felt appropriate by the treating clinician , with no set protocol . The primary objective of the trial is to compare intensive management with st and ard care  in terms of the proportion of patients achieving an ACR 20 response at 48 weeks post-r and omisation , in order to determine whether intensive management has superior clinical efficacy . Key secondary outcomes include ACR 50 and 70 , PASI 75 and X-ray Van der Heijde score at 48 weeks post-r and omisation along with cost-effectiveness at 12 , 24 and 28 weeks . Discussion The TICOPA trial will provide direct evidence as to whether the use of early and intensive treatment in PsA in routine clinical care leads to an improvement in patients ’ disease activity and a reduction in radiological joint damage . Trial registration IS RCT N30147736 , 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 Background Published pharmaceutical industry – sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favor drug over placebo . Little is known about potential biases in drug – drug comparisons . This study examined associations between research funding source , study design characteristics aim ed at reducing bias , and other factors that potentially influence results and conclusions in r and omized controlled trials ( RCTs ) of statin – drug comparisons . Methods and Findings This is a cross-sectional study of 192 published RCTs comparing a statin drug to another statin drug or non-statin drug .  Data on concealment of allocation , selection bias , blinding , sample size , disclosed funding source , financial ties of authors , results for primary outcomes , and author conclusions were extracted by two coders ( weighted kappa 0.80 to 0.97 ) . Univariate and multivariate logistic regression identified associations between independent variables and favorable results and conclusions . Of the RCTs , 50 % ( 95/192 ) were funded by industry , and 37 % ( 70/192 ) did not disclose any funding source . Looking at the totality of available evidence , we found that almost all studies ( 98 % , 189/192 ) used only surrogate outcome measures . Moreover , study design weaknesses common to published statin – drug comparisons included inadequate blinding , lack of concealment of allocation , poor follow-up , and lack of intention-to-treat analyses . In multivariate analysis of the full sample , trials with adequate blinding were less likely to report results favoring the test drug , and sample size was associated with favorable conclusions when controlling for other factors . In multivariate analysis of industry-funded RCTs , funding from the test drug company was associated with results ( odds ratio = 20.16 [ 95 % confidence interval 4.37–92.98 ] , p < 0.001 ) and conclusions ( odds ratio = 34.55 [ 95 % confidence interval 7.09–168.4 ] , p < 0.001 ) that favor the test drug when controlling for other factors . Studies with adequate blinding were less likely to report statistically significant results favoring the test drug . Conclusions RCTs of head-to-head comparisons of statins with other drugs are more likely to report results and conclusions favoring the sponsor 's product compared to the comparator drug . This bias in drug – drug comparison trials should be considered when making decisions regarding drug choice Objective . To assess longer-term outcomes , including enthesitis and dactylitis , in patients with active psoriatic arthritis ( PsA ) , in a study of golimumab treatment . Methods . Adult patients with active PsA were r and omized 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 . All patients received golimumab 50 mg or 100 mg from Week 24 onward . Entheses tenderness was scored in 15 body sites using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score ( MASES ) . Dactylitis was assessed in 20 digits of the h and s and feet . Results . Among the 405 r and omized patients , 77 % presented with enthesitis and 34 % dactylitis at baseline . At Week 24 of the placebo-controlled study phase , significant differences were observed between golimumab 50 mg and /or 100 mg and placebo for mean percent improvement in the PsA-modified MASES [ 46 % ( p < 0.001 ) and 52 % ( p < 0.001 ) vs 13 % , respectively ] and the dactylitis score [ 66 % ( p = 0.09 ) and 82 % ( p < 0.001 ) vs 28 % , respectively ] . By Week 52 , improvements were maintained among patients r and omized to receive golimumab ( mean improvements of 54 % for PsA-modified MASES and 77 % for the dactylitis score ) . Those given placebo who had enthesitis or dactylitis at baseline and who crossed over to golimumab at Week 16 or 24 had somewhat less improvement at Week 52 ( i.e. , 39 % for the PsA-modified MASES , 57 % for dactylitis score ) . Conclusion . Treatment of PsA patients with the TNF inhibitor golimumab was effective across all components of disease , including enthesitis and dactylitis , and efficacy was maintained over longer-term followup Introduction Anti-TNF therapies represent a breakthrough in the treatment of severe psoriatic arthritis . However , little is known about long-term drug persistence with these treatments in patients with psoriatic arthritis in routine clinical practice . The aim of this study was to assess persistence with first-course and second-course treatment with anti-TNF agents in a prospect i ve cohort of psoriatic arthritis patients and to identify factors associated with and reasons for drug discontinuation . Methods A total of 566 patients with psoriatic arthritis were registered with the British Society for Rheumatology Biologics Register ( first anti-TNF agent : etanercept , n = 316 ; infliximab , n = 162 ; and adalimumab , n = 88 ) . Treating physicians completed 6-monthly follow-up question naires detailing changes to anti-TNF therapies .  Persistence with treatment was examined using Kaplan – Meier survival analysis . Reasons for withdrawal were classified as due to inefficacy , adverse events or other reasons . Univariate and multivariate Cox proportional hazard models were developed to examine potential predictors of withdrawals due to inefficacy or adverse events , using a range of demographic , baseline disease-specific and therapeutic variables . Results At baseline , the mean ( st and ard deviation ) age of patients was 45.7 ( 11.1 ) years , 53 % were female and the mean disease duration was 12.4 ( 8.7 ) years . Persistence data were available for a mean ( st and ard deviation ) follow-up of 2.3 ( 0.9 ) person-years . In total , 422 patients had completed at least 12 months of follow-up , 75.5 % of whom remained on their first anti-TNF drug while 9.5 % discontinued due to inefficacy , 10.0 % due to adverse events and 5.0 % due to other reasons . During the period of follow-up , 178 patients received a second anti-TNF therapy . The survivor function on second anti-TNF  for switchers was 74 % at 12 months . Conclusions Psoriatic arthritis patients show high persistence rates with both initial and second anti-TNF therapies 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 OBJECTIVE To demonstrate the safety and efficacy of adalimumab for the treatment of active psoriatic arthritis ( PsA ) in patients with an inadequate response to disease modifying antirheumatic drugs ( DMARD ) . METHODS In a placebo controlled , double-blind , r and omized , multicenter study , patients were treated for 12 weeks with subcutaneous injections of adalimumab 40 mg every other week ( eow ) or placebo , followed by a period of open-label treatment with adalimumab 40 mg eow . The primary efficacy endpoint was the percentage of patients who met the American College of Rheumatology ( ACR20 ) core criteria at Week 12 . Secondary efficacy measures included the modified Psoriatic Arthritis Response Criteria ( PsARC ) and assessment s of disability , psoriatic lesions , and quality of life . For missing data , nonresponder imputation was used for ACR and PsARC scores and last observation carried forward for other measures . RESULTS A total of 100 patients received study drug ( 51  adalimumab  , 49 placebo )  . At Week 12 , an ACR20 response was achieved by 39 % of adalimumab patients versus 16 % of placebo patients ( p = 0.012 ) , and a PsARC response was achieved by 51 % with adalimumab versus 24 % with placebo ( p = 0.007 ) . At Week 12 , measures of skin lesions and disability were statistically significantly improved with adalimumab . After Week 12 , open-label adalimumab provided continued improvement for adalimumab patients and initiated rapid improvement for placebo patients , with ACR20 response rates of 65 % and 57 % , respectively , observed at Week 24 . Serious adverse events had similar frequencies during therapy with placebo ( 4.1 % ) , blinded adalimumab ( 2.0 % ) , and open-label adalimumab ( 3.1 % ) . No serious infections occurred during adalimumab therapy . CONCLUSION In this study of patients who had active PsA and a previous , inadequate response to DMARD therapy , adalimumab was well tolerated and significantly reduced the signs , symptoms , and disability of PsA during 12 weeks of blinded and 12 weeks of open-label therapy . Adalimumab also improved psoriasis in these patients Ro 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment OBJECTIVE Clinical and radiographic responses were evaluated in patients with psoriatic arthritis ( PsA ) treated for up to 2 years with etanercept .  METHODS Patients were previously r and omized to receive placebo or etanercept  in a double-blind study and chose to participate in the current open-label extension phase . All patients received etanercept 25 mg twice weekly . Radiographic progression was determined at baseline , 1 year , and 2 years using the Sharp method modified to include joints frequently affected in PsA. Arthritis and psoriasis responses were determined using American College of Rheumatology 20 % ( ACR20 ) improvement criteria , PsA response criteria ( PsARC ) , and the psoriasis area severity index ( PASI ) . RESULTS Of 205 patients r and omized , 169 entered open-label , and 141 [ 71 r and omized to receive placebo ( placebo/etanercept ) and 70 r and omized to receive etanercept ( etanercept/etanercept ) ]  had radiographic data available for analysis at 2 years . ACR20 criteria , PsARC , and PASI 50 criteria were met by 64 % , 84 % , and 62 % , respectively , of etanercept/etanercept patients at the end of the 48-week open-label period . Placebo/etanercept patients achieved comparable results within 12 weeks that were sustained at 48 weeks ( 63 % , 80 % , and 73 % ) . Radiographic progression was inhibited in the etanercept/ etanercept patients ( mean adjusted change in total Sharp score of -0.38 from baseline to 2 yrs ) . In placebo/etanercept patients , disease progression was inhibited once patients began receiving etanercept ( mean adjusted change of -0.22 from 1 year to 2 years ) . Adverse event rates were similar to those observed during r and omized phase , with only one serious adverse event deemed possibly related to etanercept . CONCLUSION These data demonstrate a sustained benefit of etanercept treatment , including inhibition of radiographic progression , in patients with 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 To evaluate the effect of golimumab on physical function , health‐related quality of life ( HRQOL ) , and productivity in psoriatic arthritis ( PsA ) OBJECTIVE To evaluate the effect of infliximab on progression of structural damage over 1 year in patients with active psoriatic arthritis ( PsA ) enrolled in the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2 . METHODS In this double-blind , placebo-controlled study , 200 patients with active PsA were r and omly assigned ( 1:1 ratio ) to receive infusions of infliximab ( 5 mg/kg ) or placebo at weeks 0 , 2 , and 6 , and every 8 weeks thereafter through week 54 . At week 24 , patients initially assigned to receive placebo crossed over to receive infliximab ( 5 mg/kg ) . Based on predefined criteria , patients r and omized to receive placebo could enter early escape by receiving infliximab ( 5 mg/kg ) starting at week 16 , and patients r and omized to receive infliximab could have the dose increased to 10 mg/kg starting at week 38 . Patients were analyzed according to the treatment they were r and omized to receive . Radiographs of h and s and feet were obtained at baseline and at weeks 24 and 54 . Two readers blinded to treatment assignment and radiograph sequence independently evaluated erosions and joint space narrowing using the Sharp/van der Heijde scoring method modified for PsA. RESULTS At week 24 , patients r and omized to receive infliximab 5 mg/kg had significantly less radiographic progression compared with patients r and omized to receive placebo , with mean + /- SD changes from baseline in the total Sharp/van der Heijde score of -0.70 + /- 2.53 and 0.82 + /- 2.62 , respectively ( P < 0.001 ) . At week 54 , mean + /- SD changes from baseline in the total Sharp/van der Heijde score were -0.94 + /- 3.40 in patients r and omized to receive infliximab and 0.53 + /- 2.60 in those receiving placebo/infliximab ( P = 0.001 ) . CONCLUSION Infliximab significantly inhibits radiographic progression in patients with PsA as early as 6 months after starting treatment , and the beneficial effect continues through 1 year of infliximab therapy Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist . However , the spectrum of spondylarthropathy is wider than the sum of these disorders suggests . Seronegative oligoarthritis , dactylitis or polyarthritis of the lower extremities , heel pain due to enthesitis , and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria . In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy , we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases . The diagnoses were based on the local clinical expert 's opinion . The 403 patients included 168 with ankylosing spondylitis , 68 with psoriatic arthritis , 41 with reactive arthritis , 17 with inflammatory bowel disease and arthritis , and 109 with unclassified spondylarthropathy . Based on statistical analysis and clinical reasoning , we propose the following classification criteria for spondylarthropathy : inflammatory spinal pain or synovitis ( asymmetric or predominantly in the lower limbs ) , together with at least 1 of the following : positive family history , psoriasis , inflammatory bowel disease , urethritis , or acute diarrhea , alternating buttock pain , enthesopathy , or sacroiliitis as determined from radiography of the pelvic region . These criteria result ed in a sensitivity of 87 % and a specificity of 87 % . The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers . However , we regard them as preliminary until they have been further evaluated in other setting Objective : Infliximab is effective in improving signs and symptoms of joint/skin involvement , functional status , and quality of life in patients with psoriatic arthritis ( PsA ) . Using IMPACT trial data , we assessed the effect of infliximab ( IFX ) on structural damage in PsA. Methods : Patients with active PsA were r and omly assigned to receive placebo ( PBO/IFX ) or infliximab 5 mg/kg ( IFX/IFX ) at weeks 0 , 2 , 6 , and 14 , with the primary endpoint at week 16 . The PBO group received infliximab loading doses at weeks 16 , 18 , and 22 . Thereafter , all patients received infliximab 5 mg/kg every 8 weeks through week 50 . H and /feet radiographs were obtained at weeks 0 and 50 . Total radiographic scores were determined using the PsA modified van der Heijde-Sharp ( vdH-S ) score . Projected annual rate of progression was calculated by dividing x ray score by disease duration ( years ) . Results : As reported previously , 65 % of infliximab treated patients versus 10 % of PBO treated patients achieved an ACR20 response at week 16 ( p<0.001 ) . At week 50 , 69 % of patients achieved an ACR20 response . Radiographs ( baseline and week 50 ) were available for 72/104 patients . At baseline , estimated mean annual rate of progression was 5.8 modified vdH-S points/year . Mean ( median ) changes from baseline to week 50 in the total modified vdH-S score were −1.95 ( −0.50 ) for PBO/IFX and −1.52 ( −0.50 ) for IFX/IFX patients ( p = NS ) . At week 50 , 85 % and 84 % of patients in the PBO/IFX and IFX/IFX groups had no worsening in the total modified vdH-S score . Conclusion : Infliximab inhibits radiographic progression in patients with PsA through week 50 OBJECTIVE To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis ( PsA ) and to construct new criteria from observed data . METHODS Data were collected prospect ively from consecutive clinic attendees with PsA and other inflammatory arthropathies . Subjects were classified by each of 7 criteria . Sensitivity and specificity were compared using conditional logistic regression analysis . Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold st and ard definition of " case"-ness . Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria , which were then constructed using a receiver operating characteristic curve . RESULTS Data were collected on 588 cases and 536 controls with rheumatoid arthritis ( n = 384 ) , ankylosing spondylitis ( n = 72 ) , undifferentiated arthritis ( n = 38 ) , connective tissue disorders ( n = 14 ) , and other diseases ( n = 28 ) . The specificity of each set of criteria was high . The sensitivity of the Vasey and Espinoza method ( 0.97 ) was similar to that of the method of McGonagle et al ( 0.98 ) and greater than that of the methods of Bennett ( 0.44 ) , Moll and Wright ( 0.91 ) , the European Spondylarthropathy Study Group ( 0.74 ) , and Gladman et al ( 0.91 ) . The CASPAR ( ClASsification criteria for Psoriatic ARthritis ) criteria consisted of established inflammatory articular disease with at least 3 points from the following features : current psoriasis ( assigned a score of 2 ; all other features were assigned a score of 1 ) , a history of psoriasis ( unless current psoriasis was present ) , a family history of psoriasis ( unless current psoriasis was present or there was a history of psoriasis ) , dactylitis , juxtaarticular new bone formation , rheumatoid factor negativity , and nail dystrophy . These criteria were more specific ( 0.987 versus 0.960 ) but less sensitive ( 0.914 versus 0.972 ) than those of Vasey and Espinoza . CONCLUSION The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria Objectives : To evaluate the effect of infliximab on health related quality of life ( HRQoL ) and physical function in patients with active psoriatic arthritis ( PsA ) in the IMPACT 2 trial . Methods : 200 patients with PsA unresponsive to conventional treatment were r and omised to intravenous 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 .  HRQoL was assessed using the Short Form-36 ( SF-36 ) at weeks 0 , 14 , and 24 . Functional disability was assessed using the Health Assessment Question naire ( HAQ ) at every visit through week 24 . Associations between changes in quality of life ( SF-36 ) and articular ( American College of Rheumatology ( ACR ) ) and dermatological ( Psoriasis Area and Severity Index ( PASI ) ) responses were examined . Results : Mean percentage improvement from baseline in HAQ was 48.6 % in the infliximab group compared with worsening of 18.4 % in the placebo group at week 14 ( p<0.001 ) . Furthermore , 58.6 % and 19.4 % of infliximab and placebo treated patients , respectively , achieved a clinical ly meaningful improvement in HAQ ( that is , ⩾0.3 unit decrease ) at week 14 ( p<0.001 ) . Increases in physical and mental component summary ( PCS and MCS ) scores and all eight scales of the SF-36 in the infliximab group were greater than those in the placebo group at week 14 ( p⩽0.001 ) . These benefits were sustained through week 24 . Patients achieving ACR20 and PASI75 responses had the greatest improvements in PCS and MCS scores . Conclusions : In patients with PsA  , infliximab 5 mg/kg significantly improved HRQoL and physical function compared with placebo through 24 weeks OBJECTIVE To investigate longterm efficacy/safety of infliximab over 2 years in patients with active psoriatic arthritis ( PsA ) . METHODS Initially , 104 patients were r and omized to receive blinded infusions of infliximab 5 mg/kg or placebo at Weeks 0 , 2 , 6 , and 14 . At Week 16 , all patients received infliximab 5 mg/kg every 8 weeks through Week 46 . Seventy-eight of the 87 patients completing the first year continued into the open-label longterm extension and received infliximab 5 mg/kg at Weeks 54 , 62 , 70 , 78 , 86 , and 94 . The primary efficacy endpoint for the study extension was the proportion of patients with at least 20 % improvement in the American College of Rheumatology response criteria ( ACR20 ) at Week 98 . Radiographic progression was assessed by the PsA-modified van der Heijde-Sharp score in patients with radiographs available at baseline and Week 98 ( n = 43 ) . RESULTS At Week 98 , 62 % ( 48/78 ) of infliximab-treated patients achieved an ACR20 response ; 45 % ( 35/78 ) and 35 % ( 27/78 ) of patients achieved ACR50 and ACR70 responses , respectively . Among patients with baseline Psoriasis Area and Severity Index scores > or= 2.5 , 64 % ( 16/25 ) achieved > 75 % improvement from baseline to Week 98 . The average estimated annual radiographic progression with infliximab treatment was significantly reduced versus the estimated baseline rate of progression . No new safety issues were observed during the second year of the study . CONCLUSION Therapy with infliximab 5 mg/kg through Week 94 produced sustained improvement in joint and skin symptoms , inhibited radiographic progression , and continued to exhibit a favorable benefit-risk ratio in this population with treatment-refractory OBJECTIVE To determine whether sulfasalazine ( SSZ ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis ( PsA ) resistant to nonsteroidal antiinflammatory drug therapy . METHODS Two hundred twenty-one patients with PsA were recruited from 15 clinics , r and omized ( double-blind ) to SSZ or placebo treatment , and followed up for 36 weeks . Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessment s. RESULTS Longitudinal analysis revealed a trend favoring SSZ treatment ( P = 0.13 ) . At the end of treatment , response rates were 57.8 % for SSZ compared with 44.6 % for placebo ( P = 0.05 ) . The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo ( P < 0.0001 ) . Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints , including dyspepsia , nausea , vomiting , and diarrhea . CONCLUSION SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with An investigation of clinical and laboratory variables which might form the basis for judging disease activity in clinical practice was made by six rheumatologists in a prospect i ve study of up to three years ' duration of 113 patients with early rheumatoid arthritis . Decisions to start treatment with slow acting antirheumatic drugs were equated with moments of high disease activity . If treatment with slow acting antirheumatic drugs was not started or if the slow acting antirheumatic drug remained unchanged for at least one year or if treatment was stopped because of disease remission , this was equated with periods of low disease activity . Two groups , one with high and one with low disease activity according to the above criteria , were formed . Factor analysis was performed to enable easy h and ling of the large number of clinical and laboratory variables without loss of information ; this result ed in five factors . Next , discriminant analysis was done to determine to what extent each factor contributed to discrimination between the two groups of differing disease activity . Finally , a multiple regression analysis was carried out to determine which laboratory and clinical variables underlie the factors of the discriminant function , result ing in a ' disease activity score ' . This score consisted of the following variables : Ritchie index , swollen joints , erythrocyte sedimentation rate , and general health , in declining importance . The rheumatologists ' decisions to prescribe slow acting antirheumatic drugs , or not , were mainly based on articular symptoms Objective : To evaluate the effects of adalimumab on patient-reported outcomes of joint-related and skin-related functional impairment , health-related quality of life , fatigue and pain in patients with psoriatic arthritis ( PsA ) . Methods : Patients with moderately- to severely- active PsA were treated with adalimumab , 40 mg , every other week , or placebo , in this 24-week , r and omised , controlled trial . Patient-reported outcomes included the Health Assessment Question naire Disability Index ( HAQ DI ) , Short-Form 36 Health Survey ( SF-36 ) , the Functional Assessment of Chronic Illness Therapy — Fatigue ( FACIT-Fatigue ) Scale and the Dermatology Life Quality Index ( DLQI ) . Results : Adalimumab ( n = 151 ) and placebo ( n = 162 ) groups were comparable with respect to baseline demographics and disease severity . Significant changes from baseline in HAQ DI were reported for adalimumab v placebo ( −0.4 v −0.1 , p<0.001 ) at both 12 and 24 weeks . At week 24 , significant improvements in the SF-36 domains of physical functioning , role-physical , bodily pain , general health , vitality and social functioning , as well as the physical component summary score , were observed for adalimumab versus placebo ( p<0.01 ) . These reported changes in HAQ DI and SF-36 were also clinical ly important . Significantly more patients treated with adalimumab had complete resolution of functional loss ( HAQ DI = 0 ) and dermatological-related functional limitations ( DLQI = 0 ) compared with placebo at weeks 12 and 24 ( p⩽0.001 ) . Adalimumab led to significantly greater improvements in FACIT-Fatigue scores , pain scores , and disease activity measures versus placebo at 12 and 24 weeks ( p<0.001 for all ) . Conclusions : Adalimumab improved physical-related and dermatological-related functional limitations , HRQOL , fatigue and pain in patients with PsA treated for 24 weeks OBJECTIVE To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis ( PsA ) . METHODS One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug ( DMARD ) had failed were recruited into this investigator-initiated , multicenter , r and omized , double-blind , placebo-controlled clinical trial . During the initial blinded portion of the study , patients received infusions of infliximab ( 5 mg/kg ) or placebo at weeks 0 , 2 , 6 , and 14 . After week 16 , patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50 , while patients initially r and omized to infliximab continued to receive active treatment at the same dose through week 50 . The primary efficacy outcome was achievement of the American College of Rheumatology 20 % criteria for improvement in rheumatoid arthritis ( ACR20 ) at week 16 . Additional predefined clinical efficacy assessment s included the Psoriasis Area and Severity Index ( PASI ) score , the ACR50 and ACR70 criteria , the Disease Activity Score in 28 joints , the Health Assessment Question naire , ratings of enthesitis and dactylitis , and the Psoriatic Arthritis Response Criteria score . RESULTS The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 ( 65 % ) was significantly higher than the proportion of placebo-treated patients who achieved this response ( 10 % ) . In addition , 46 % of infliximab-treated patients achieved an ACR50 response , and 29 % achieved an ACR70 response ; no placebo-treated patient achieved these end points . Among patients who had PASI scores of > /=2.5 at baseline , 68 % of infliximab-treated patients achieved improvement of > /=75 % in the PASI score at week 16 compared with none of the placebo-treated patients . Continued therapy with infliximab result ed in sustained improvement in articular and dermatologic manifestations of PsA through week 50 . The incidence of adverse events was similar between the treatment groups . CONCLUSION Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis , psoriasis , dactylitis , and enthesitis in patients with active PsA that had been resistant to DMARD therapy . With continued infliximab treatment , benefits were sustained through 50 weeks . The benefit-to-risk ratio appeared favorable in this study population OBJECTIVE Etanercept has been shown to improve the articular and cutaneous manifestations of psoriatic arthritis ( PsA ) . In this study , we further evaluated the safety , efficacy , and effect on radiographic progression of etanercept in patients with PsA. METHODS Patients with PsA ( n = 205 ) were r and omized to receive placebo or 25 mg etanercept subcutaneously twice weekly for 24 weeks . Patients continued to receive blind-labeled therapy in a maintenance phase until all had completed the 24-week phase , then could receive open-label etanercept in a 48-week extension . Efficacy and safety were evaluated at 4 , 12 , and 24 weeks and at 12-week intervals thereafter . Radiographs of the h and s and wrists were assessed at baseline and 24 weeks , at entry to the open-label phase , and after 48 weeks in the study . RESULTS Etanercept significantly reduced the signs and symptoms of PsA and psoriasis . At 12 weeks , 59 % of etanercept patients met the American College of Rheumatology 20 % improvement criteria for joint response , compared with 15 % of placebo patients ( P < 0.0001 ) , and results were sustained at 24 and 48 weeks . At 24 weeks , 23 % of etanercept patients eligible for psoriasis evaluation achieved at least 75 % improvement in the Psoriasis Area and Severity Index , compared with 3 % of placebo patients ( P = 0.001 ) . Radiographic disease progression was inhibited in the etanercept group at 12 months ; the mean annualized rate of change in the modified total Sharp score was -0.03 unit , compared with + 1.00 unit in the placebo group ( P = 0.0001 ) . Etanercept was well tolerated . CONCLUSION Etanercept reduced joint symptoms , improved psoriatic lesions , inhibited radiographic progression , and was well tolerated in patients with 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
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