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: BACKGROUND Previous studies of infliximab in psoriasis have demonstrated rapid improvement with induction therapy and sustained response with regularly administered maintenance therapy . OBJECTIVE The efficacy and safety of continuous ( every-8-week ) and intermittent ( as-needed ) maintenance regimens were compared . METHODS Patients with moderate-to-severe psoriasis ( n = 835 ) were r and omized to induction therapy ( weeks 0 , 2 , and 6 ) with infliximab 3 mg/kg or 5 mg/kg or placebo . Infliximab-treated patients were r and omized again at week 14 to continuous or intermittent maintenance regimens at their induction dose . RESULTS At week 10 , 75.5 % and 70.3 % of patients in the infliximab 5 mg/kg and 3 mg/kg groups , respectively , achieved PASI 75 ; 45.2 % and 37.1 % achieved PASI 90 ( vs 1.9 % [ PASI 75 ] and 0.5 % [ PASI 90 ] for placebo ; P < .001 ) . Through week 50 , PASI responses were better maintained with continuous compared with intermittent therapy within each dose , and with 5 mg/kg compared with 3 mg/kg continuous therapy . LIMITATIONS Longer term ( > 1 year ) maintenance therapy and further study of  infliximab serum concentrations over this period , in both PASI 75 responders and non-responders , would be preferable . CONCLUSIONS Through week 50 , response was best maintained with continuous infliximab therapy . Infliximab was generally well-tolerated in most patients Abstract Apremilast , an oral , small‐molecule phosphodiesterase 4 inhibitor , works intracellularly within immune cells to regulate inflammatory mediators . This phase 2b r and omized , placebo‐controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis . In total , 254 patients were r and omized to placebo , apremilast 20 mg b.i.d . ( apremilast 20 ) or apremilast 30 mg b.i.d . ( apremilast 30 ) through week 16 ; thereafter , all placebo patients were re‐r and omized to apremilast 20 or 30 through week 68 . Efficacy assessment s included achievement of 75 % or more reduction from baseline in Psoriasis Area and Severity Index score ( PASI‐75 ; primary ) and achievement of static Physician Global Assessment ( sPGA ; secondary ) score of 0 ( clear ) or 1 ( minimal ) at week 16 . Safety was assessed through week 68 . At week 16 , PASI‐75 response rates were 7.1 % ( placebo ) , 23.5 % ( apremilast 20 ; P = 0.0032 vs placebo ) and 28.2 % ( apremilast 30 ; P = 0.0003 vs placebo ) ; sPGA response rates ( score of 0 or 1 ) were 8.8 % ( placebo ) , 23.9 % ( apremilast 20 ; P = 0.0165 vs placebo ) and 29.6 % ( apremilast 30 ; P = 0.0020 vs placebo ) . Responses were maintained with apremilast through week 68 . Most common adverse events ( AEs ) with placebo , apremilast 20 and apremilast 30 ( 0–16 weeks ) were nasopharyngitis ( 8.3 % , 11.8 % , 11.8 % ) , diarrhea ( 1.2 % , 8.2 % , 9.4 % ) , and abdominal discomfort ( 1.2 % , 1.2 % , 7.1 % ) , respectively . Exposure‐adjusted incidence of these AEs did not increase with continued apremilast treatment ( up to 68 weeks ) . Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies Background Apremilast , an oral , small‐molecule phosphodiesterase 4 inhibitor , has demonstrated efficacy in patients with moderate‐to‐severe psoriasis . Objective Evaluate efficacy and safety of apremilast vs. placebo in biologic‐naive patients with moderate‐to‐severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb , r and omized , double‐blind , placebo‐controlled study ( NCT01690299 ) . Methods Two hundred and fifty patients were r and omized to placebo ( n = 84 ) , apremilast 30 mg BID ( n = 83 ) or etanercept 50 mg QW ( n = 83 ) through Week 16 ; thereafter , all patients continued or switched to apremilast through Week 104 . The primary efficacy endpoint was achievement of PASI‐75 at Week 16 with apremilast vs. placebo . Secondary endpoints included achievement of PASI‐75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16 . Outcomes were assessed through Week 52 . This study was not design ed for apremilast vs. etanercept comparisons . Results At Week 16 , PASI‐75 achievement was greater with apremilast ( 39.8 % ) vs. placebo ( 11.9 % ; P < 0.0001 ) ; 48.2 % of patients achieved PASI‐75  with etanercept ( P < 0.0001 vs. placebo ) . PASI‐75 response was maintained in 47.3 % ( apremilast/apremilast ) , 49.4 % ( etanercept/apremilast ) and 47.9 % ( placebo/apremilast ) of patients at Week 52 . Most common adverse events ( ≥5 % ) with apremilast , including nausea , diarrhoea , upper respiratory tract infection , nasopharyngitis , tension headache and headache , were mild or moderate in severity ; diarrhoea and nausea generally resolved in the first month . No new safety or tolerability issues were observed through Week 52 with apremilast . Conclusion Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic‐naive patients with psoriasis , which was sustained over 52 weeks , and demonstrated safety consistent with the known safety profile of apremilast . Switching from etanercept to apremilast did not result in any new or clinical ly significant safety findings , and efficacy was maintained with apremilast through Week 52 Background The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies . The IL‐12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study BACKGROUND Inflammatory cytokines such as tumor necrosis factor ( TNF ) have been implicated in the pathogenesis of psoriasis . We evaluated the safety and efficacy of etanercept , a TNF antagonist , for the treatment of plaque psoriasis . METHODS In this 24-week , double-blind study , 672 patients underwent r and omization and 652 either received placebo or received etanercept subcutaneously at a low dose ( 25 mg once weekly ) , a medium dose ( 25 mg twice weekly ) , or a high dose ( 50 mg twice weekly ) . After 12 weeks , patients in the placebo group began twice-weekly treatment with 25 mg of etanercept . The primary measure of clinical response was the psoriasis area- and -severity index . RESULTS At week 12 , there was an improvement from base line of 75 percent or more in the psoriasis area- and -severity index in 4 percent of the patients in the placebo group , as compared with 14 percent of those in the low-dose -- etanercept group , 34 percent in the medium-dose -- etanercept group , and 49 percent in the high-dose-etanercept group ( P<0.001 for all three comparisons with the placebo group ) . The clinical responses continued to improve with longer treatment . At week 24 , there was at least a 75 percent improvement in the psoriasis area- and -severity index in 25 percent of the patients in the low-dose group , 44 percent of those in the medium-dose group , and 59 percent in the high-dose group . The responses as measured by improvements in the psoriasis area- and -severity index were paralleled by improvements in global assessment s by physicians and the patients and in quality -of-life measures .  Etanercept was generally well tolerated . CONCLUSIONS The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks BACKGROUND New therapeutic options are needed for patients with psoriasis .  Tofacitinib , an oral Janus kinase inhibitor , is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis . In this study , we aim ed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population . METHODS In this phase 3 , r and omised , multicentre , double-dummy , placebo-controlled , 12-week , non-inferiority trial , adult patients with chronic stable plaque psoriasis ( for ≥12 months ) who were c and i date s for systemic or phototherapy and had a Psoriasis Area and Severity Index ( PASI ) score of 12 or higher and a Physician 's Global Assessment ( PGA ) of moderate or severe , and had failed to respond to , had a contraindication to , or were intolerant to at least one conventional systemic therapy , were enrolled from 122 investigational dermatology centres worldwide . Eligible patients were r and omly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals , etanercept 50 mg subcutaneously twice weekly at about 3 - 4 day intervals , or placebo . R and omisation was done by a computer-generated r and omisation schedule , and all patients and study personnel were masked to treatment assignment . The co- primary endpoints were the proportion of patients at week 12 with at least a 75 % reduction in the PASI score from baseline ( PASI75 response ) and the proportion of patients achieving a PGA score of " clear " or " almost clear " ( PGA response ) , analysed in the full analysis set ( all patients who were r and omised and received at least one dose of study drug ) . This study is registered with Clinical Trials.gov , number NCT01241591 . FINDINGS Between Nov 29 , 2010 , and Sept 13 , 2012 , we enrolled 1106 eligible adult patients with chronic plaque psoriasis and r and omly assigned them to the four treatment groups ( 330 to tofacitinib 5 mg twice daily , 332 to tofacitinib 10 mg twice daily , 336 to etanercept 50 mg twice weekly , and 108 to placebo ) . Of these patients , 1101 actually received their assigned study medication ( 329 in the tofactinib 5 mg group , 330 in the tofacitinib 10 mg group , 335 in the etanercept group , and 107 in the placebo group ) . At week 12 , PASI75 responses were recorded in 130 ( 39·5 % ) of 329 patients in the tofacitinib 5 mg group , 210 ( 63·6 % ) of 330 in the tofacitinib 10 mg group , 197 ( 58·8 % ) of 335 in the etanercept group , and six ( 5·6 % ) of 107 in the placebo group . A PGA response was achieved by 155 ( 47·1 % ) of 329 patients in the tofacitinib 5 mg group , 225 ( 68·2 % ) of 330 in the tofacitinib 10 mg group , 222 ( 66·3 % ) of 335 in the etanercept group , and 16 ( 15·0 % ) of 107 in the placebo group . The rate of adverse events was similar across the four groups , with serious adverse events occurring in seven ( 2 % ) of 329 patients in the tofacitinib 5 mg group , five ( 2 % ) of 330 in the tofacitinib 10 mg group , seven ( 2 % ) of 335 in the etanercept group , and two ( 2 % ) of 107 in the placebo group . Three ( 1 % ) of 329 patients in the tofacitinib 5 mg group , ten ( 3 % ) of 330 in the tofacitinib 10 mg group , 11 ( 3 % ) of 335 in the etanercept group , and four 
    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: BACKGROUND Previous studies of infliximab in psoriasis have demonstrated rapid improvement with induction therapy and sustained response with regularly administered maintenance therapy . OBJECTIVE The efficacy and safety of continuous ( every-8-week ) and intermittent ( as-needed ) maintenance regimens were compared . METHODS Patients with moderate-to-severe psoriasis ( n = 835 ) were r and omized to induction therapy ( weeks 0 , 2 , and 6 ) with infliximab 3 mg/kg or 5 mg/kg or placebo . Infliximab-treated patients were r and omized again at week 14 to continuous or intermittent maintenance regimens at their induction dose . RESULTS At week 10 , 75.5 % and 70.3 % of patients in the infliximab 5 mg/kg and 3 mg/kg groups , respectively , achieved PASI 75 ; 45.2 % and 37.1 % achieved PASI 90 ( vs 1.9 % [ PASI 75 ] and 0.5 % [ PASI 90 ] for placebo ; P < .001 ) . Through week 50 , PASI responses were better maintained with continuous compared with intermittent therapy within each dose , and with 5 mg/kg compared with 3 mg/kg continuous therapy . LIMITATIONS Longer term ( > 1 year ) maintenance therapy and further study of  infliximab serum concentrations over this period , in both PASI 75 responders and non-responders , would be preferable . CONCLUSIONS Through week 50 , response was best maintained with continuous infliximab therapy . Infliximab was generally well-tolerated in most patients Abstract Apremilast , an oral , small‐molecule phosphodiesterase 4 inhibitor , works intracellularly within immune cells to regulate inflammatory mediators . This phase 2b r and omized , placebo‐controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis . In total , 254 patients were r and omized to placebo , apremilast 20 mg b.i.d . ( apremilast 20 ) or apremilast 30 mg b.i.d . ( apremilast 30 ) through week 16 ; thereafter , all placebo patients were re‐r and omized to apremilast 20 or 30 through week 68 . Efficacy assessment s included achievement of 75 % or more reduction from baseline in Psoriasis Area and Severity Index score ( PASI‐75 ; primary ) and achievement of static Physician Global Assessment ( sPGA ; secondary ) score of 0 ( clear ) or 1 ( minimal ) at week 16 . Safety was assessed through week 68 . At week 16 , PASI‐75 response rates were 7.1 % ( placebo ) , 23.5 % ( apremilast 20 ; P = 0.0032 vs placebo ) and 28.2 % ( apremilast 30 ; P = 0.0003 vs placebo ) ; sPGA response rates ( score of 0 or 1 ) were 8.8 % ( placebo ) , 23.9 % ( apremilast 20 ; P = 0.0165 vs placebo ) and 29.6 % ( apremilast 30 ; P = 0.0020 vs placebo ) . Responses were maintained with apremilast through week 68 . Most common adverse events ( AEs ) with placebo , apremilast 20 and apremilast 30 ( 0–16 weeks ) were nasopharyngitis ( 8.3 % , 11.8 % , 11.8 % ) , diarrhea ( 1.2 % , 8.2 % , 9.4 % ) , and abdominal discomfort ( 1.2 % , 1.2 % , 7.1 % ) , respectively . Exposure‐adjusted incidence of these AEs did not increase with continued apremilast treatment ( up to 68 weeks ) . Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies Background Apremilast , an oral , small‐molecule phosphodiesterase 4 inhibitor , has demonstrated efficacy in patients with moderate‐to‐severe psoriasis . Objective Evaluate efficacy and safety of apremilast vs. placebo in biologic‐naive patients with moderate‐to‐severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb , r and omized , double‐blind , placebo‐controlled study ( NCT01690299 ) . Methods Two hundred and fifty patients were r and omized to placebo ( n = 84 ) , apremilast 30 mg BID ( n = 83 ) or etanercept 50 mg QW ( n = 83 ) through Week 16 ; thereafter , all patients continued or switched to apremilast through Week 104 . The primary efficacy endpoint was achievement of PASI‐75 at Week 16 with apremilast vs. placebo . Secondary endpoints included achievement of PASI‐75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16 . Outcomes were assessed through Week 52 . This study was not design ed for apremilast vs. etanercept comparisons . Results At Week 16 , PASI‐75 achievement was greater with apremilast ( 39.8 % ) vs. placebo ( 11.9 % ; P < 0.0001 ) ; 48.2 % of patients achieved PASI‐75  with etanercept ( P < 0.0001 vs. placebo ) . PASI‐75 response was maintained in 47.3 % ( apremilast/apremilast ) , 49.4 % ( etanercept/apremilast ) and 47.9 % ( placebo/apremilast ) of patients at Week 52 . Most common adverse events ( ≥5 % ) with apremilast , including nausea , diarrhoea , upper respiratory tract infection , nasopharyngitis , tension headache and headache , were mild or moderate in severity ; diarrhoea and nausea generally resolved in the first month . No new safety or tolerability issues were observed through Week 52 with apremilast . Conclusion Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic‐naive patients with psoriasis , which was sustained over 52 weeks , and demonstrated safety consistent with the known safety profile of apremilast . Switching from etanercept to apremilast did not result in any new or clinical ly significant safety findings , and efficacy was maintained with apremilast through Week 52 Background The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies . The IL‐12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study BACKGROUND Inflammatory cytokines such as tumor necrosis factor ( TNF ) have been implicated in the pathogenesis of psoriasis . We evaluated the safety and efficacy of etanercept , a TNF antagonist , for the treatment of plaque psoriasis . METHODS In this 24-week , double-blind study , 672 patients underwent r and omization and 652 either received placebo or received etanercept subcutaneously at a low dose ( 25 mg once weekly ) , a medium dose ( 25 mg twice weekly ) , or a high dose ( 50 mg twice weekly ) . After 12 weeks , patients in the placebo group began twice-weekly treatment with 25 mg of etanercept . The primary measure of clinical response was the psoriasis area- and -severity index . RESULTS At week 12 , there was an improvement from base line of 75 percent or more in the psoriasis area- and -severity index in 4 percent of the patients in the placebo group , as compared with 14 percent of those in the low-dose -- etanercept group , 34 percent in the medium-dose -- etanercept group , and 49 percent in the high-dose-etanercept group ( P<0.001 for all three comparisons with the placebo group ) . The clinical responses continued to improve with longer treatment . At week 24 , there was at least a 75 percent improvement in the psoriasis area- and -severity index in 25 percent of the patients in the low-dose group , 44 percent of those in the medium-dose group , and 59 percent in the high-dose group . The responses as measured by improvements in the psoriasis area- and -severity index were paralleled by improvements in global assessment s by physicians and the patients and in quality -of-life measures .  Etanercept was generally well tolerated . CONCLUSIONS The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks BACKGROUND New therapeutic options are needed for patients with psoriasis .  Tofacitinib , an oral Janus kinase inhibitor , is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis . In this study , we aim ed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population . METHODS In this phase 3 , r and omised , multicentre , double-dummy , placebo-controlled , 12-week , non-inferiority trial , adult patients with chronic stable plaque psoriasis ( for ≥12 months ) who were c and i date s for systemic or phototherapy and had a Psoriasis Area and Severity Index ( PASI ) score of 12 or higher and a Physician 's Global Assessment ( PGA ) of moderate or severe , and had failed to respond to , had a contraindication to , or were intolerant to at least one conventional systemic therapy , were enrolled from 122 investigational dermatology centres worldwide . Eligible patients were r and omly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals , etanercept 50 mg subcutaneously twice weekly at about 3 - 4 day intervals , or placebo . R and omisation was done by a computer-generated r and omisation schedule , and all patients and study personnel were masked to treatment assignment . The co- primary endpoints were the proportion of patients at week 12 with at least a 75 % reduction in the PASI score from baseline ( PASI75 response ) and the proportion of patients achieving a PGA score of " clear " or " almost clear " ( PGA response ) , analysed in the full analysis set ( all patients who were r and omised and received at least one dose of study drug ) . This study is registered with Clinical Trials.gov , number NCT01241591 . FINDINGS Between Nov 29 , 2010 , and Sept 13 , 2012 , we enrolled 1106 eligible adult patients with chronic plaque psoriasis and r and omly assigned them to the four treatment groups ( 330 to tofacitinib 5 mg twice daily , 332 to tofacitinib 10 mg twice daily , 336 to etanercept 50 mg twice weekly , and 108 to placebo ) . Of these patients , 1101 actually received their assigned study medication ( 329 in the tofactinib 5 mg group , 330 in the tofacitinib 10 mg group , 335 in the etanercept group , and 107 in the placebo group ) . At week 12 , PASI75 responses were recorded in 130 ( 39·5 % ) of 329 patients in the tofacitinib 5 mg group , 210 ( 63·6 % ) of 330 in the tofacitinib 10 mg group , 197 ( 58·8 % ) of 335 in the etanercept group , and six ( 5·6 % ) of 107 in the placebo group . A PGA response was achieved by 155 ( 47·1 % ) of 329 patients in the tofacitinib 5 mg group , 225 ( 68·2 % ) of 330 in the tofacitinib 10 mg group , 222 ( 66·3 % ) of 335 in the etanercept group , and 16 ( 15·0 % ) of 107 in the placebo group . The rate of adverse events was similar across the four groups , with serious adverse events occurring in seven ( 2 % ) of 329 patients in the tofacitinib 5 mg group , five ( 2 % ) of 330 in the tofacitinib 10 mg group , seven ( 2 % ) of 335 in the etanercept group , and two ( 2 % ) of 107 in the placebo group . Three ( 1 % ) of 329 patients in the tofacitinib 5 mg group , ten ( 3 % ) of 330 in the tofacitinib 10 mg group , 11 ( 3 % ) of 335 in the etanercept group , and four 
    Output:
    