human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Background : Psoriatic arthritis often affects patients with psoriasis . Objective : To examine the effect of adalimumab on psoriatic arthritis in patients with moderate to severe psoriasis . Methods : Data from patients with psoriasis and a reported history of comorbid psoriatic arthritis in 3 r and omized , placebo-controlled psoriasis trials of  adalimumab were analyzed . Results : Adalimumab ( n = 274 ) reduced the risk of psoriatic arthropathy adverse events by 75 % versus placebo ( 1.1 vs. 4.8 % ; p = 0.025 ) . Psoriasis/psoriatic arthritis-related pain was significantly reduced ( –31.3 vs. –5.6 visual analog scale units ; p < 0.0001 ) . At week 16 , adalimumab-treated patients were more likely to respond ( 56.9 vs. 4.5 % ; p < 0.001 ) and responded for a greater percentage of follow-up time ( 39.3 vs. 2.9 % ; p < 0.0001 ) than placebo-treated patients ( regression model for PASI 75 and ACR 20 responses ) . Conclusion : Adalimumab treatment of moderate to severe psoriasis reduced symptoms of comorbid psoriatic arthritis 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 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 DESIGN AND INTERVENTION This trial was an international multicenter phase III , double-blind , placebo-controlled , r and omized , parallel group study . Patients with active PsA were r and omly allocated to infusions of either 5 mg/kg infliximab or placebo at baseline and then at 2 , 6 , 14 and 22 weeks . R and omization was stratified by baseline methotrexate use . Dactylitis in the h and s and feet and enthesitis in the feet were assessed . Antinuclear-antibody ( ANA ) and antidouble-str and ed-DNA-antibody titers and the frequency of antibodies to infliximab were measured at baseline and at week 22 Objective : To determine which of the changes in synovial tissue correlates best with clinical response associated with effective therapy ( adalimumab ) to facilitate the planning of future studies with therapeutic agents for psoriatic arthritis ( PsA ) . Methods : A total of 24 patients with active PsA were r and omised to receive adalimumab ( n = 12 ) or placebo ( n = 12 ) for 4 weeks . Synovial biopsies were obtained before and after 4 weeks of treatment . Immunohistochemical analysis was performed to characterise the cell infiltrate , expression of cytokines and matrix metalloproteinases ( MMPs ) and vascularity . Sections were analysed by digital image analysis . Statistical analysis was performed using covariance analysis . Results : The mean Disease Activity Score in 28 joints ( DAS28 ) after 4 weeks was 1.92 units lower ( 95 % confidence interval ( CI ) 1.07 to 2.77 ) after adalimumab therapy compared with placebo . Paired pretreatment and post-treatment synovial sample s were available from 19 patients . Many cell types were reduced after adalimumab treatment compared to placebo . After applying a ranked analysis of covariance ( ANCOVA ) model to correct for baseline imbalances , a significant effect of treatment was observed on CD3-positive cells : there was a median reduction of 248 cells/mm2 after adalimumab versus placebo treatment ( p = 0.035 ) . In addition , the expression of MMP13 was significantly reduced after active treatment : the integrated optical density (IOD)/mm2 was 18 190 lower after adalimumab treatment as compared to placebo ( p = 0.033 ) . Conclusion : Adalimumab therapy in PsA is associated with a marked reduction in T cell infiltration and MMP13 expression in synovial tissue , suggesting that these parameters could be used as biomarkers that are sensitive to change after active treatment in small proof of concept studies in 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 , ps 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Background : Psoriatic arthritis often affects patients with psoriasis . Objective : To examine the effect of adalimumab on psoriatic arthritis in patients with moderate to severe psoriasis . Methods : Data from patients with psoriasis and a reported history of comorbid psoriatic arthritis in 3 r and omized , placebo-controlled psoriasis trials of  adalimumab were analyzed . Results : Adalimumab ( n = 274 ) reduced the risk of psoriatic arthropathy adverse events by 75 % versus placebo ( 1.1 vs. 4.8 % ; p = 0.025 ) . Psoriasis/psoriatic arthritis-related pain was significantly reduced ( –31.3 vs. –5.6 visual analog scale units ; p < 0.0001 ) . At week 16 , adalimumab-treated patients were more likely to respond ( 56.9 vs. 4.5 % ; p < 0.001 ) and responded for a greater percentage of follow-up time ( 39.3 vs. 2.9 % ; p < 0.0001 ) than placebo-treated patients ( regression model for PASI 75 and ACR 20 responses ) . Conclusion : Adalimumab treatment of moderate to severe psoriasis reduced symptoms of comorbid psoriatic arthritis 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 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 DESIGN AND INTERVENTION This trial was an international multicenter phase III , double-blind , placebo-controlled , r and omized , parallel group study . Patients with active PsA were r and omly allocated to infusions of either 5 mg/kg infliximab or placebo at baseline and then at 2 , 6 , 14 and 22 weeks . R and omization was stratified by baseline methotrexate use . Dactylitis in the h and s and feet and enthesitis in the feet were assessed . Antinuclear-antibody ( ANA ) and antidouble-str and ed-DNA-antibody titers and the frequency of antibodies to infliximab were measured at baseline and at week 22 Objective : To determine which of the changes in synovial tissue correlates best with clinical response associated with effective therapy ( adalimumab ) to facilitate the planning of future studies with therapeutic agents for psoriatic arthritis ( PsA ) . Methods : A total of 24 patients with active PsA were r and omised to receive adalimumab ( n = 12 ) or placebo ( n = 12 ) for 4 weeks . Synovial biopsies were obtained before and after 4 weeks of treatment . Immunohistochemical analysis was performed to characterise the cell infiltrate , expression of cytokines and matrix metalloproteinases ( MMPs ) and vascularity . Sections were analysed by digital image analysis . Statistical analysis was performed using covariance analysis . Results : The mean Disease Activity Score in 28 joints ( DAS28 ) after 4 weeks was 1.92 units lower ( 95 % confidence interval ( CI ) 1.07 to 2.77 ) after adalimumab therapy compared with placebo . Paired pretreatment and post-treatment synovial sample s were available from 19 patients . Many cell types were reduced after adalimumab treatment compared to placebo . After applying a ranked analysis of covariance ( ANCOVA ) model to correct for baseline imbalances , a significant effect of treatment was observed on CD3-positive cells : there was a median reduction of 248 cells/mm2 after adalimumab versus placebo treatment ( p = 0.035 ) . In addition , the expression of MMP13 was significantly reduced after active treatment : the integrated optical density (IOD)/mm2 was 18 190 lower after adalimumab treatment as compared to placebo ( p = 0.033 ) . Conclusion : Adalimumab therapy in PsA is associated with a marked reduction in T cell infiltration and MMP13 expression in synovial tissue , suggesting that these parameters could be used as biomarkers that are sensitive to change after active treatment in small proof of concept studies in 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 , ps 
    Output:
    