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 Ixekizumab , a monoclonal antibody that selectively targets interleukin-17A , has been established as safe and effective in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis . The lifetime incidence of psoriatic nail disease is 80%-90 % of patients , and approximately 50 % of patients with psoriasis have nail involvement . MATERIAL S AND METHODS The design of UNCOVER-3 , a Phase 3 , multicenter , double-blind , placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab for moderate to severe psoriasis , has been published previously . Patients were r and omized to receive blinded placebo , etanercept ( 50 mg twice weekly ) or 80 mg ixekizumab every 2 weeks ( IXEQ2W ) or every 4 weeks ( IXEQ4W ) for 12 weeks . At week 12 , all patients were assigned to open-label ixekizumab 80 mg every 4 weeks through week 60 . In this 60-week post hoc subset analysis , we evaluated only those patients with significant baseline nail involvement , defined as fingernail NAPSI ≥16 and at least 4 fingernails involved .  RESULTS Ixekizumab Q2W or Q4W result ed in greater improvement in nail psoriasis than placebo or etanercept by week 12 of administration , as measured by percent NAPSI reduction ( IXEQ2W 39 % improvement , IXEQ4W 40 % , etanercept 28 % , placebo -4.7 % ) . At week 24 , significantly more patients receiving ixekizumab exhibited no signs of nail involvement ( IXEQ2W/Q4W 34 % , IXEQ4W/Q4W 30 % ) . Similar gains were observed at 60 weeks in all treatment groups . CONCLUSION Ixekizumab led to improvement in fingernail psoriasis by week 12 compared with placebo . Continued improvement in fingernail psoriasis with ixekizumab was observed , with > 50 % of patients achieving complete fingernail psoriasis resolution ( NAPSI=0 ) at week 60 . J Drugs Dermatol . 2016;15(8):958 - 961 BACKGROUND Brodalumab ( anti-interleukin-17-receptor antibody ) was effective in treating moderate to severe psoriasis in a 12-week , dose-ranging , placebo-controlled trial . OBJECTIVE We sought to evaluate efficacy and safety of long-term brodalumab treatment . METHODS In this interim analysis at week 120 of an open-label extension study , patients received brodalumab 210 mg every 2 weeks . Protocol amendments reduced the dose ( 140 mg ) in patients weighing 100 kg or less and subsequently increased the dose ( 210 mg ) in patients with inadequate responses . Efficacy was measured by static physician global assessment and 75 % or greater , 90 % or greater , or 100 % improvement in Psoriasis Area and Severity Index score ( PASI-75 , PASI-90 , and PASI-100 , respectively ) . RESULTS Of 181 patients , 144 completed week 120 .  Static physician global assessment scores of clear/almost clear and clear were achieved by 90 % and 63 % of patients , respectively , at week 12 and by 72 % and 51 % at week 120 . The PASI-75 , PASI-90 , and PASI-100 response rates at week 12 ( 95%/85%/63 % ) were sustained through week 120 ( 86%/70%/51 % ) . Most commonly reported adverse events were nasopharyngitis ( 26.5 % ) , upper respiratory tract infection ( 19.9 % ) , arthralgia ( 16.0 % ) , and back pain ( 11.0 % ) . Four patients had grade -2 absolute neutrophil count . LIMITATIONS There was no control group in this open-label extension . CONCLUSION Brodalumab demonstrated sustained clinical response and an acceptable safety profile through 120 weeks in patients with moderate to severe psoriasis BACKGROUND Tildrakizumab is a high-affinity , humanised , IgG1 κ antibody targeting interleukin 23 p19 that represents an evolving treatment strategy in chronic plaque psoriasis . Previous research suggested clinical improvement with inhibition of interleukin 23 p19 . We did two phase 3 trials to investigate whether tildrakizumab is superior to placebo and etanercept in the treatment of chronic plaque psoriasis . METHODS We did two three-part , parallel group , double-blind , r and omised controlled studies , reSURFACE 1 ( at 118 sites in Australia , Canada , Japan , the UK , and the USA ) and reSURFACE 2 ( at 132 sites in Europe , Israel , and the USA ) . Participants aged 18 years or older with moderate-to-severe chronic plaque psoriasis ( body surface area involvement ≥10 % , Physician 's Global Assessment [ PGA ] score ≥3 , and Psoriasis Area and Severity Index [ PASI ] score ≥12 ) were r and omised ( via interactive voice and web response system ) to tildrakizumab 200 mg , tildrakizumab 100 mg , or placebo in reSURFACE 1 ( 2:2:1 ) , or to tildrakizumab 200 mg , tildrakizumab 100 mg , placebo , or etanercept 50 mg ( 2:2:1:2 ) . R and omisation was done by region and stratified for bodyweight ( ≤90 kg or > 90 kg ) and previous exposure to biologics therapy for psoriasis . Investigators , participants , and study personnel were blinded to group allocation and remained blinded until completion of the studies . Assigned medication was identical in appearance and packaging . Tildrakizumab was administered subcutaneously at weeks 0 and 4 during part 1 and at week 16 during part 2 ( weeks 12 and 16 for participants re-r and omised from placebo to tildrakizumab ; etanercept was given twice weekly in part 1 of reSURFACE 2 and once weekly during part 2 ) . The co- primary endpoints were the proportion of patients achieving PASI 75 and PGA response ( score of 0 or 1 with ≥2 grade score reduction from baseline ) at week 12 . Safety was assessed in the all- participants -as-treated population , and efficacy in the full- analysis set . These trials are registered with Clinical Trials.gov , numbers NCT01722331 ( reSURFACE 1 ) and NCT01729754 ( reSURFACE 2 ) . These studies are completed , but extension studies are ongoing . FINDINGS reSURFACE 1 ran from Dec 10 , 2012 , to Oct 28 , 2015 . reSURFACE 2 ran from Feb 12 , 2013 , to Sept 28 , 2015 . In reSURFACE 1 , 772 patients were r and omly assigned , 308 to tildrakizumab 200 mg , 309 to tildrakizumab 100 mg , and 155 to placebo . At week 12 , 192 patients ( 62 % ) in the 200 mg group and 197 patients ( 64 % ) in the 100 mg group achieved PASI 75 , compared with 9 patients ( 6 % ) in the placebo group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ) . 182 patients ( 59 % ) in the 200 mg group and 179 patients ( 58 % ) in the 100 mg group achieved PGA responses , compared with 11 patients ( 7 % ) in the placebo group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ) . In reSURFACE 2 , 1090 patients were r and omly assigned , 314 to tildrakizumab 200 mg , 307 to tildrakizumab 100 mg , 156 to placebo , and 313 to etanercept . At week 12 , 206 patients ( 66 % ) in the 200 mg group , and 188 patients ( 61 % ) in the 100 mg group achieved PASI 75 , compared with 9 patients ( 6 % ) in the placebo group and 151 patients ( 48 % ) in the etanercept group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ; p<0·0001 for 200 mg vs etanercept and p=0·0010 for 100 mg vs etanercept ) . 186 patients ( 59 % ) in the 200 mg group , and 168 patients ( 59 % ) [ corrected ] in the 100 mg group achieved a PGA response , compared with 7 patients ( 4 % ) in the placebo group and 149 patients ( 48 % ) in the etanercept group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ; p=0·0031 for 200 mg vs etanercept and p=0·0663 for 100 mg vs etanercept ) . Serious adverse events were similar and low in all groups in both trials . One patient died in reSURFACE 2 , in the tildrakizumab 100 mg group ; the patient had alcoholic cardiomyopathy and steatohepatitis , and adjudication was unable to determine the cause of death . INTERPRETATION In two phase 3 trials , tildrakizumab 200 mg and 100 mg were efficacious compared with placebo and etanercept and were well tolerated in the treatment of patients with moderate-to-severe chronic plaque psoriasis . FUNDING Merck & The interleukin‐17 cytokine family plays a central role in psoriasis pathogenesis Aims To assess safety , pharmacokinetics ( PK ) and clinical efficacy of bimekizumab ( formerly UCB4940 ) , a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)‐17A and IL‐17F , in subjects with mild plaque psoriasis . Methods R and omized , double‐blind , first‐in‐human study of bimekizumab in 39 subjects who received single‐dose intravenous bimekizumab ( 8–640 mg ) or placebo ( NCT02529956 ) .  Results Bimekizumab demonstrated dose‐proportional linear PK and was tolerated across the dose range assessed . No subject discontinued due to treatment‐emergent adverse events and no severe adverse events were reported . Bimekizumab demonstrated fast onset of clinical ly‐meaningful effects on skin of patients with mild psoriasis  as early as Week 2 . Maximal improvements ( 100 % or near 100 % reductions from baseline ) in all measures of disease activity were observed between Weeks 8–12 in subjects receiving 160–640 mg bimekizumab . The duration of effect at doses ≥160 mg was evident up to Weeks 12–20 after a single intravenous dose , dependent on endpoint . Conclusions This is the first study to demonstrate the safety , tolerability and clinical efficacy of a dual IL‐17A and IL‐17F inhibitor , in subjects with mild psoriasis .  Bimekizumab showed fast onset of clinical ly‐meaningful efficacy by Week 2 , with a maximal or near‐maximal magnitude of response that was maintained up to study Weeks 12–20 . These findings support the continued clinical development of bimekizumab for diseases mediated by both IL‐17A and IL‐17F , including psoriasis Objective The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn 's disease . Design In a double-blind , r and omised , placebo-controlled proof-of-concept study , 59 patients with moderate to severe Crohn 's disease ( Crohn 's Disease Activity Index ( CDAI ) ≥220 to ≤450 ) were assigned in a 2:1 ratio to 2 × 10 mg/kg intravenous secukinumab or placebo . The primary end point , addressed by Bayesian statistics augmented with historical placebo information , was the probability that secukinumab reduces the CDAI by ≥50 points more than placebo at week 6 . Ancillary analyses explored associations of 35 c and i date genetic polymorphisms and faecal calprotectin response . Results 59 patients ( 39 secukinumab , 20 placebo , mean baseline CDAI 307 and 301 , respectively ) were recruited . 18/59 ( 31 % ) patients discontinued prematurely ( 12/39 ( 31 % ) sec 
    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 Ixekizumab , a monoclonal antibody that selectively targets interleukin-17A , has been established as safe and effective in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis . The lifetime incidence of psoriatic nail disease is 80%-90 % of patients , and approximately 50 % of patients with psoriasis have nail involvement . MATERIAL S AND METHODS The design of UNCOVER-3 , a Phase 3 , multicenter , double-blind , placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab for moderate to severe psoriasis , has been published previously . Patients were r and omized to receive blinded placebo , etanercept ( 50 mg twice weekly ) or 80 mg ixekizumab every 2 weeks ( IXEQ2W ) or every 4 weeks ( IXEQ4W ) for 12 weeks . At week 12 , all patients were assigned to open-label ixekizumab 80 mg every 4 weeks through week 60 . In this 60-week post hoc subset analysis , we evaluated only those patients with significant baseline nail involvement , defined as fingernail NAPSI ≥16 and at least 4 fingernails involved .  RESULTS Ixekizumab Q2W or Q4W result ed in greater improvement in nail psoriasis than placebo or etanercept by week 12 of administration , as measured by percent NAPSI reduction ( IXEQ2W 39 % improvement , IXEQ4W 40 % , etanercept 28 % , placebo -4.7 % ) . At week 24 , significantly more patients receiving ixekizumab exhibited no signs of nail involvement ( IXEQ2W/Q4W 34 % , IXEQ4W/Q4W 30 % ) . Similar gains were observed at 60 weeks in all treatment groups . CONCLUSION Ixekizumab led to improvement in fingernail psoriasis by week 12 compared with placebo . Continued improvement in fingernail psoriasis with ixekizumab was observed , with > 50 % of patients achieving complete fingernail psoriasis resolution ( NAPSI=0 ) at week 60 . J Drugs Dermatol . 2016;15(8):958 - 961 BACKGROUND Brodalumab ( anti-interleukin-17-receptor antibody ) was effective in treating moderate to severe psoriasis in a 12-week , dose-ranging , placebo-controlled trial . OBJECTIVE We sought to evaluate efficacy and safety of long-term brodalumab treatment . METHODS In this interim analysis at week 120 of an open-label extension study , patients received brodalumab 210 mg every 2 weeks . Protocol amendments reduced the dose ( 140 mg ) in patients weighing 100 kg or less and subsequently increased the dose ( 210 mg ) in patients with inadequate responses . Efficacy was measured by static physician global assessment and 75 % or greater , 90 % or greater , or 100 % improvement in Psoriasis Area and Severity Index score ( PASI-75 , PASI-90 , and PASI-100 , respectively ) . RESULTS Of 181 patients , 144 completed week 120 .  Static physician global assessment scores of clear/almost clear and clear were achieved by 90 % and 63 % of patients , respectively , at week 12 and by 72 % and 51 % at week 120 . The PASI-75 , PASI-90 , and PASI-100 response rates at week 12 ( 95%/85%/63 % ) were sustained through week 120 ( 86%/70%/51 % ) . Most commonly reported adverse events were nasopharyngitis ( 26.5 % ) , upper respiratory tract infection ( 19.9 % ) , arthralgia ( 16.0 % ) , and back pain ( 11.0 % ) . Four patients had grade -2 absolute neutrophil count . LIMITATIONS There was no control group in this open-label extension . CONCLUSION Brodalumab demonstrated sustained clinical response and an acceptable safety profile through 120 weeks in patients with moderate to severe psoriasis BACKGROUND Tildrakizumab is a high-affinity , humanised , IgG1 κ antibody targeting interleukin 23 p19 that represents an evolving treatment strategy in chronic plaque psoriasis . Previous research suggested clinical improvement with inhibition of interleukin 23 p19 . We did two phase 3 trials to investigate whether tildrakizumab is superior to placebo and etanercept in the treatment of chronic plaque psoriasis . METHODS We did two three-part , parallel group , double-blind , r and omised controlled studies , reSURFACE 1 ( at 118 sites in Australia , Canada , Japan , the UK , and the USA ) and reSURFACE 2 ( at 132 sites in Europe , Israel , and the USA ) . Participants aged 18 years or older with moderate-to-severe chronic plaque psoriasis ( body surface area involvement ≥10 % , Physician 's Global Assessment [ PGA ] score ≥3 , and Psoriasis Area and Severity Index [ PASI ] score ≥12 ) were r and omised ( via interactive voice and web response system ) to tildrakizumab 200 mg , tildrakizumab 100 mg , or placebo in reSURFACE 1 ( 2:2:1 ) , or to tildrakizumab 200 mg , tildrakizumab 100 mg , placebo , or etanercept 50 mg ( 2:2:1:2 ) . R and omisation was done by region and stratified for bodyweight ( ≤90 kg or > 90 kg ) and previous exposure to biologics therapy for psoriasis . Investigators , participants , and study personnel were blinded to group allocation and remained blinded until completion of the studies . Assigned medication was identical in appearance and packaging . Tildrakizumab was administered subcutaneously at weeks 0 and 4 during part 1 and at week 16 during part 2 ( weeks 12 and 16 for participants re-r and omised from placebo to tildrakizumab ; etanercept was given twice weekly in part 1 of reSURFACE 2 and once weekly during part 2 ) . The co- primary endpoints were the proportion of patients achieving PASI 75 and PGA response ( score of 0 or 1 with ≥2 grade score reduction from baseline ) at week 12 . Safety was assessed in the all- participants -as-treated population , and efficacy in the full- analysis set . These trials are registered with Clinical Trials.gov , numbers NCT01722331 ( reSURFACE 1 ) and NCT01729754 ( reSURFACE 2 ) . These studies are completed , but extension studies are ongoing . FINDINGS reSURFACE 1 ran from Dec 10 , 2012 , to Oct 28 , 2015 . reSURFACE 2 ran from Feb 12 , 2013 , to Sept 28 , 2015 . In reSURFACE 1 , 772 patients were r and omly assigned , 308 to tildrakizumab 200 mg , 309 to tildrakizumab 100 mg , and 155 to placebo . At week 12 , 192 patients ( 62 % ) in the 200 mg group and 197 patients ( 64 % ) in the 100 mg group achieved PASI 75 , compared with 9 patients ( 6 % ) in the placebo group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ) . 182 patients ( 59 % ) in the 200 mg group and 179 patients ( 58 % ) in the 100 mg group achieved PGA responses , compared with 11 patients ( 7 % ) in the placebo group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ) . In reSURFACE 2 , 1090 patients were r and omly assigned , 314 to tildrakizumab 200 mg , 307 to tildrakizumab 100 mg , 156 to placebo , and 313 to etanercept . At week 12 , 206 patients ( 66 % ) in the 200 mg group , and 188 patients ( 61 % ) in the 100 mg group achieved PASI 75 , compared with 9 patients ( 6 % ) in the placebo group and 151 patients ( 48 % ) in the etanercept group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ; p<0·0001 for 200 mg vs etanercept and p=0·0010 for 100 mg vs etanercept ) . 186 patients ( 59 % ) in the 200 mg group , and 168 patients ( 59 % ) [ corrected ] in the 100 mg group achieved a PGA response , compared with 7 patients ( 4 % ) in the placebo group and 149 patients ( 48 % ) in the etanercept group ( p<0·0001 for comparisons of both tildrakizumab groups vs placebo ; p=0·0031 for 200 mg vs etanercept and p=0·0663 for 100 mg vs etanercept ) . Serious adverse events were similar and low in all groups in both trials . One patient died in reSURFACE 2 , in the tildrakizumab 100 mg group ; the patient had alcoholic cardiomyopathy and steatohepatitis , and adjudication was unable to determine the cause of death . INTERPRETATION In two phase 3 trials , tildrakizumab 200 mg and 100 mg were efficacious compared with placebo and etanercept and were well tolerated in the treatment of patients with moderate-to-severe chronic plaque psoriasis . FUNDING Merck & The interleukin‐17 cytokine family plays a central role in psoriasis pathogenesis Aims To assess safety , pharmacokinetics ( PK ) and clinical efficacy of bimekizumab ( formerly UCB4940 ) , a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)‐17A and IL‐17F , in subjects with mild plaque psoriasis . Methods R and omized , double‐blind , first‐in‐human study of bimekizumab in 39 subjects who received single‐dose intravenous bimekizumab ( 8–640 mg ) or placebo ( NCT02529956 ) .  Results Bimekizumab demonstrated dose‐proportional linear PK and was tolerated across the dose range assessed . No subject discontinued due to treatment‐emergent adverse events and no severe adverse events were reported . Bimekizumab demonstrated fast onset of clinical ly‐meaningful effects on skin of patients with mild psoriasis  as early as Week 2 . Maximal improvements ( 100 % or near 100 % reductions from baseline ) in all measures of disease activity were observed between Weeks 8–12 in subjects receiving 160–640 mg bimekizumab . The duration of effect at doses ≥160 mg was evident up to Weeks 12–20 after a single intravenous dose , dependent on endpoint . Conclusions This is the first study to demonstrate the safety , tolerability and clinical efficacy of a dual IL‐17A and IL‐17F inhibitor , in subjects with mild psoriasis .  Bimekizumab showed fast onset of clinical ly‐meaningful efficacy by Week 2 , with a maximal or near‐maximal magnitude of response that was maintained up to study Weeks 12–20 . These findings support the continued clinical development of bimekizumab for diseases mediated by both IL‐17A and IL‐17F , including psoriasis Objective The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn 's disease . Design In a double-blind , r and omised , placebo-controlled proof-of-concept study , 59 patients with moderate to severe Crohn 's disease ( Crohn 's Disease Activity Index ( CDAI ) ≥220 to ≤450 ) were assigned in a 2:1 ratio to 2 × 10 mg/kg intravenous secukinumab or placebo . The primary end point , addressed by Bayesian statistics augmented with historical placebo information , was the probability that secukinumab reduces the CDAI by ≥50 points more than placebo at week 6 . Ancillary analyses explored associations of 35 c and i date genetic polymorphisms and faecal calprotectin response . Results 59 patients ( 39 secukinumab , 20 placebo , mean baseline CDAI 307 and 301 , respectively ) were recruited . 18/59 ( 31 % ) patients discontinued prematurely ( 12/39 ( 31 % ) sec 
    Output:
    