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 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 Background This study was part of a large national cost‐effectiveness analysis , and was funded by the National Fund for Investigational Medicine of the Health Care Insurance Board . Objective To develop new composite disease activity indices for psoriatic arthritis ( PsA ) . Methods Data from routine clinic visits at multiple centres were collected in a systematic manner . Data included all domains identified as important in r and omised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity . New indices were developed by multiple linear regression ( psoriatic arthritis disease activity score : PASDAS ) and empirically , utilising physician-defined cut-offs for disease activity ( arithmetic mean of desirability functions : AMDF ) . These were compared with existing composite measures : Composite Psoriatic arthritis Disease Activity Index ( CPDAI ) , Disease Activity for PSoriatic Arthritis ( DAPSA ) , and Disease Activity Score for rheumatoid arthritis ( DAS28 ) . Results 161/503 ( 32 % ) subjects had treatment changes . Although all measures performed well , compared with existing indices , PASDAS was better able to discriminate between high and low disease activity ( area under receiver operating curves ( ROC ) ) curve with 95 % CI : PASDAS 0.773 ( 0.723 , 0.822 ) ; AMDF 0.730 ( 0.680 , 0.780 ) ; CPDAI 0.719 ( 0.668 , 0.770 ) ; DAPSA 0.710 ( 0.654 , 0.766 ) ; DAS28 0.736 ( 0.680 , 0.792 ) . All measures were able to discriminate between disease activity states in patients with oligoarthritis , although area under the receiver operating curves ( AUC ) were generally smaller . In patients with severe skin disease ( psoriasis area and severity index > 10 ) both nonparametric and AUC curve statistics were nonsignificant for all measures . Conclusions Two new composite measures to assess disease activity in PsA have been developed . Further testing in other data sets , including comparison with existing measures , is required to vali date these instruments 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 Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed 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 
    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 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 Background This study was part of a large national cost‐effectiveness analysis , and was funded by the National Fund for Investigational Medicine of the Health Care Insurance Board . Objective To develop new composite disease activity indices for psoriatic arthritis ( PsA ) . Methods Data from routine clinic visits at multiple centres were collected in a systematic manner . Data included all domains identified as important in r and omised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity . New indices were developed by multiple linear regression ( psoriatic arthritis disease activity score : PASDAS ) and empirically , utilising physician-defined cut-offs for disease activity ( arithmetic mean of desirability functions : AMDF ) . These were compared with existing composite measures : Composite Psoriatic arthritis Disease Activity Index ( CPDAI ) , Disease Activity for PSoriatic Arthritis ( DAPSA ) , and Disease Activity Score for rheumatoid arthritis ( DAS28 ) . Results 161/503 ( 32 % ) subjects had treatment changes . Although all measures performed well , compared with existing indices , PASDAS was better able to discriminate between high and low disease activity ( area under receiver operating curves ( ROC ) ) curve with 95 % CI : PASDAS 0.773 ( 0.723 , 0.822 ) ; AMDF 0.730 ( 0.680 , 0.780 ) ; CPDAI 0.719 ( 0.668 , 0.770 ) ; DAPSA 0.710 ( 0.654 , 0.766 ) ; DAS28 0.736 ( 0.680 , 0.792 ) . All measures were able to discriminate between disease activity states in patients with oligoarthritis , although area under the receiver operating curves ( AUC ) were generally smaller . In patients with severe skin disease ( psoriasis area and severity index > 10 ) both nonparametric and AUC curve statistics were nonsignificant for all measures . Conclusions Two new composite measures to assess disease activity in PsA have been developed . Further testing in other data sets , including comparison with existing measures , is required to vali date these instruments 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 Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed 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 
    Output:
    