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 assess the safety and efficacy of ixekizumab , a monoclonal antibody that inhibits interleukin-17A , in a double-blind phase III trial enrolling patients with active psoriatic arthritis ( PsA ) . Methods Patients naive to biologic therapy with active PsA were r and omised to subcutaneous injections of placebo ( N=106 ) , adalimumab 40 mg once every 2 weeks ( active reference ; N=101 ) , ixekizumab 80 mg once every 2 weeks ( IXEQ2W ) ( N=103 ) , or ixekizumab 80 mg once every 4 weeks ( IXEQ4W ) ( N=107 ) . Both ixekizumab regimens included a 160-mg starting dose . The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 ( ACR20 ) response at week 24 . Results Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W ( 62.1 % ) or IXEQ4W ( 57.9 % ) than placebo ( 30.2 % ) ( p≤0.001 ; non-responder imputation method ) . Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24 , and there was significantly less progression of structural damage at week 24 ( p≤0.01 ) . Clearance of plaque psoriasis was greater with ixekizumab than placebo ( p≤0.001 ) . Efficacy results with adalimumab , the active reference arm , showed significant improvements versus placebo . Treatment-emergent adverse events were more frequent with ixekizumab ( 65.7–66.4 % ) and adalimumab ( 64.4 % ) than placebo ( 47.2 % ) ( p<0.05 ) . Conclusions In biologic-naive patients with active PsA  , ixekizumab treatment result ed in improvements in disease activity and physical function , as well as in the inhibition of structural damage progression . Overall , adverse events were more frequent in all active groups compared with placebo . Trial registration number NCT01695239 ; EudraCT2011 - 002326 - 49 ; Results Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-PsA ( NCT01087788 ) , an ongoing Phase 3 trial in patients with psoriatic arthritis ( PsA ) . Methods Patients were r and omised 1:1:1 to placebo  , 200 mg CZP every 2 weeks ( Q2W ) or 400 mg CZP every 4 weeks ( Q4W ) . Patients could have had exposure to one previous tumour necrosis factor ( TNF ) inhibitor therapy . Primary endpoints were American College of Rheumatology 20 % ( ACR20 ) response at week 12 and modified Total Sharp Score change from baseline at week 24 . Secondary endpoints included ; Psoriatic Arthritis Response Criteria ( PsARC ) score , Health Assessment Question naire Disability Index ( HAQ-DI ) , Psoriasis Area and Severity Index , Leeds Enthesitis Index , Leeds Dactylitis Index , and Modified Nail Psoriasis Severity Index . Results Of 409 patients r and omised , 368 completed 24 weeks of treatment .  ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo ( 58.0 % and 51.9 % vs 24.3 % ( p<0.001 ) ) at week 12 , with improvements observed by week 1 . There was a statistically significant improvement in physical function from baseline , measured by HAQ-DI in CZP patients compared with placebo ( −0.50 vs −0.19 , p<0.001 ) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo ( 78.3 % and 77.0 % vs 33.1 % ( p<0.001 ) ) . Sustained improvements were observed in psoriatic skin involvement , enthesitis , dactylitis and nail disease . Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure . No new safety signals were observed . Conclusions Rapid improvements in the signs and symptoms of PsA , including joints , skin , enthesitis , dactylitis and nail disease were observed across both CZP dosing regimens BACKGROUND In a phase 2 study , the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis . We sought to evaluate the efficacy and safety of secukinumab , an anti-interleukin-17A monoclonal antibody , in such patients . METHODS In this double-blind , phase 3 study , 606 patients with psoriatic arthritis were r and omly assigned in a 1:1:1 ratio to receive intravenous secukinumab ( at a dose of 10 mg per kilogram ) at weeks 0 , 2 , and 4 , followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks , or placebo . Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24 , depending on clinical response . The primary end point was the proportion of patients with an American College of Rheumatology 20 ( ACR20 ) response at week 24 , defined as a 20 % improvement from baseline in the number of tender and swollen joints and at least three other important domains . RESULTS ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg ( 50.0 % ) and 75 mg ( 50.5 % ) than in those receiving placebo ( 17.3 % ) ( P<0.001 for both comparisons with placebo ) . Secondary end points , including the ACR50 response and joint structural damage , were significantly better in the secukinumab groups than in the placebo group . Improvements were sustained through 52 weeks . Infections , including c and ida , were more common in the secukinumab groups . Throughout the study ( mean secukinumab exposure , 438.5 days ; mean placebo exposure , 128.5 days ) , four patients in the secukinumab groups had a stroke ( 0.6 per 100 patient-years ; 95 % confidence interval [ CI ] , 0.2 to 1.5 ) , and two had a myocardial infa rct ion ( 0.3 per 100 patient-years ; 95 % CI , 0.0 to 1.0 ) , as compared with no patients in the placebo group . CONCLUSIONS Secukinumab was more effective than placebo in patients with psoriatic arthritis , which vali date s interleukin-17A as a therapeutic target . Infections were more common in the secukinumab groups than in the placebo group . The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use . ( Funded by Novartis Pharma ; Clinical Trials.gov number , NCT01392326 . ) Introduction Secukinumab and adalimumab are approved for adults with active psoriatic arthritis ( PsA ) . In the absence of direct r and omized controlled trial ( RCT ) data , matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve population s. Methods Individual patient data from the FUTURE 2 RCT ( secukinumab vs. placebo ; N = 299 ) were adjusted to match baseline characteristics of the ADEPT RCT ( adalimumab vs. placebo ; N = 313 ) . Logistic regression determined adjustment weights for age , body weight , sex , race , methotrexate use , psoriasis affecting ≥ 3 % of body surface area , Psoriasis Area and Severity Index score , Health Assessment Question naire Disability Index score , presence of dactylitis and enthesitis , and previous anti-TNF therapy . Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 ( placebo-adjusted ) , 16 , 24 , and 48 ( nonplacebo-adjusted ) . Results After matching , the effective sample size for FUTURE 2 was 101 . Week 12 American College of Rheumatology ( ACR ) response rates were not significantly different between secukinumab and adalimumab . Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab ( P = 0.017 , P = 0.033 ) , as was ACR 50 for secukinumab 300 mg ( P = 0.030 ) . Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab ( P = 0.001 , P = 0.019 ) , as was ACR 20 for secukinumab 300 mg ( P = 0.048 ) . Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab ( P = 0.002 , P = 0.027 ) , as was ACR 50 for secukinumab 300 mg ( P = 0.032 ) . Conclusions In our analysis , patients with PsA receiving secukinumab  were more likely to achieve higher ACR responses through 1 year ( weeks 16–48 ) than those treated with adalimumab . Although informative , these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can vali date these findings . Funding Novartis Pharma AG 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 Objectives Apremilast , an oral phosphodiesterase 4 inhibitor , regulates inflammatory mediators . Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 ( PALACE 1 ) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug ( DMARD ) and /or biologic therapy . Methods In the 24-week , placebo-controlled phase of PALACE 1 , patients ( N=504 ) were r and omised ( 1:1:1 ) to placebo , apremilast 20 mg twice a day ( BID ) or apremilast 30 mg BID . At week 16 , patients without ≥20 % reduction in swollen and tender joint counts  were required to be re-r and omised equally to either apremilast dose if initially r and omised to placebo or 
    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 assess the safety and efficacy of ixekizumab , a monoclonal antibody that inhibits interleukin-17A , in a double-blind phase III trial enrolling patients with active psoriatic arthritis ( PsA ) . Methods Patients naive to biologic therapy with active PsA were r and omised to subcutaneous injections of placebo ( N=106 ) , adalimumab 40 mg once every 2 weeks ( active reference ; N=101 ) , ixekizumab 80 mg once every 2 weeks ( IXEQ2W ) ( N=103 ) , or ixekizumab 80 mg once every 4 weeks ( IXEQ4W ) ( N=107 ) . Both ixekizumab regimens included a 160-mg starting dose . The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 ( ACR20 ) response at week 24 . Results Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W ( 62.1 % ) or IXEQ4W ( 57.9 % ) than placebo ( 30.2 % ) ( p≤0.001 ; non-responder imputation method ) . Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24 , and there was significantly less progression of structural damage at week 24 ( p≤0.01 ) . Clearance of plaque psoriasis was greater with ixekizumab than placebo ( p≤0.001 ) . Efficacy results with adalimumab , the active reference arm , showed significant improvements versus placebo . Treatment-emergent adverse events were more frequent with ixekizumab ( 65.7–66.4 % ) and adalimumab ( 64.4 % ) than placebo ( 47.2 % ) ( p<0.05 ) . Conclusions In biologic-naive patients with active PsA  , ixekizumab treatment result ed in improvements in disease activity and physical function , as well as in the inhibition of structural damage progression . Overall , adverse events were more frequent in all active groups compared with placebo . Trial registration number NCT01695239 ; EudraCT2011 - 002326 - 49 ; Results Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-PsA ( NCT01087788 ) , an ongoing Phase 3 trial in patients with psoriatic arthritis ( PsA ) . Methods Patients were r and omised 1:1:1 to placebo  , 200 mg CZP every 2 weeks ( Q2W ) or 400 mg CZP every 4 weeks ( Q4W ) . Patients could have had exposure to one previous tumour necrosis factor ( TNF ) inhibitor therapy . Primary endpoints were American College of Rheumatology 20 % ( ACR20 ) response at week 12 and modified Total Sharp Score change from baseline at week 24 . Secondary endpoints included ; Psoriatic Arthritis Response Criteria ( PsARC ) score , Health Assessment Question naire Disability Index ( HAQ-DI ) , Psoriasis Area and Severity Index , Leeds Enthesitis Index , Leeds Dactylitis Index , and Modified Nail Psoriasis Severity Index . Results Of 409 patients r and omised , 368 completed 24 weeks of treatment .  ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo ( 58.0 % and 51.9 % vs 24.3 % ( p<0.001 ) ) at week 12 , with improvements observed by week 1 . There was a statistically significant improvement in physical function from baseline , measured by HAQ-DI in CZP patients compared with placebo ( −0.50 vs −0.19 , p<0.001 ) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo ( 78.3 % and 77.0 % vs 33.1 % ( p<0.001 ) ) . Sustained improvements were observed in psoriatic skin involvement , enthesitis , dactylitis and nail disease . Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure . No new safety signals were observed . Conclusions Rapid improvements in the signs and symptoms of PsA , including joints , skin , enthesitis , dactylitis and nail disease were observed across both CZP dosing regimens BACKGROUND In a phase 2 study , the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis . We sought to evaluate the efficacy and safety of secukinumab , an anti-interleukin-17A monoclonal antibody , in such patients . METHODS In this double-blind , phase 3 study , 606 patients with psoriatic arthritis were r and omly assigned in a 1:1:1 ratio to receive intravenous secukinumab ( at a dose of 10 mg per kilogram ) at weeks 0 , 2 , and 4 , followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks , or placebo . Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24 , depending on clinical response . The primary end point was the proportion of patients with an American College of Rheumatology 20 ( ACR20 ) response at week 24 , defined as a 20 % improvement from baseline in the number of tender and swollen joints and at least three other important domains . RESULTS ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg ( 50.0 % ) and 75 mg ( 50.5 % ) than in those receiving placebo ( 17.3 % ) ( P<0.001 for both comparisons with placebo ) . Secondary end points , including the ACR50 response and joint structural damage , were significantly better in the secukinumab groups than in the placebo group . Improvements were sustained through 52 weeks . Infections , including c and ida , were more common in the secukinumab groups . Throughout the study ( mean secukinumab exposure , 438.5 days ; mean placebo exposure , 128.5 days ) , four patients in the secukinumab groups had a stroke ( 0.6 per 100 patient-years ; 95 % confidence interval [ CI ] , 0.2 to 1.5 ) , and two had a myocardial infa rct ion ( 0.3 per 100 patient-years ; 95 % CI , 0.0 to 1.0 ) , as compared with no patients in the placebo group . CONCLUSIONS Secukinumab was more effective than placebo in patients with psoriatic arthritis , which vali date s interleukin-17A as a therapeutic target . Infections were more common in the secukinumab groups than in the placebo group . The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use . ( Funded by Novartis Pharma ; Clinical Trials.gov number , NCT01392326 . ) Introduction Secukinumab and adalimumab are approved for adults with active psoriatic arthritis ( PsA ) . In the absence of direct r and omized controlled trial ( RCT ) data , matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve population s. Methods Individual patient data from the FUTURE 2 RCT ( secukinumab vs. placebo ; N = 299 ) were adjusted to match baseline characteristics of the ADEPT RCT ( adalimumab vs. placebo ; N = 313 ) . Logistic regression determined adjustment weights for age , body weight , sex , race , methotrexate use , psoriasis affecting ≥ 3 % of body surface area , Psoriasis Area and Severity Index score , Health Assessment Question naire Disability Index score , presence of dactylitis and enthesitis , and previous anti-TNF therapy . Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 ( placebo-adjusted ) , 16 , 24 , and 48 ( nonplacebo-adjusted ) . Results After matching , the effective sample size for FUTURE 2 was 101 . Week 12 American College of Rheumatology ( ACR ) response rates were not significantly different between secukinumab and adalimumab . Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab ( P = 0.017 , P = 0.033 ) , as was ACR 50 for secukinumab 300 mg ( P = 0.030 ) . Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab ( P = 0.001 , P = 0.019 ) , as was ACR 20 for secukinumab 300 mg ( P = 0.048 ) . Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab ( P = 0.002 , P = 0.027 ) , as was ACR 50 for secukinumab 300 mg ( P = 0.032 ) . Conclusions In our analysis , patients with PsA receiving secukinumab  were more likely to achieve higher ACR responses through 1 year ( weeks 16–48 ) than those treated with adalimumab . Although informative , these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can vali date these findings . Funding Novartis Pharma AG 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 Objectives Apremilast , an oral phosphodiesterase 4 inhibitor , regulates inflammatory mediators . Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 ( PALACE 1 ) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug ( DMARD ) and /or biologic therapy . Methods In the 24-week , placebo-controlled phase of PALACE 1 , patients ( N=504 ) were r and omised ( 1:1:1 ) to placebo , apremilast 20 mg twice a day ( BID ) or apremilast 30 mg BID . At week 16 , patients without ≥20 % reduction in swollen and tender joint counts  were required to be re-r and omised equally to either apremilast dose if initially r and omised to placebo or 
    Output:
    