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 evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis ( pcJIA ) . Methods This three-part , r and omised , placebo-controlled , double-blind withdrawal study ( NCT00988221 ) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate .  During part 1 , patients received open-label tocilizumab every 4 weeks ( 8 or 10 mg/kg for body weight ( BW ) < 30 kg ; 8 mg/kg for BW ≥30 kg ) . At week 16 , patients with ≥JIA-American College of Rheumatology ( ACR ) 30 improvement entered the 24-week , double-blind part 2 after r and omisation 1:1 to placebo or tocilizumab ( stratified by methotrexate and steroid background therapy ) for evaluation of the primary end point : JIA flare , compared with week 16 . Patients flaring or completing part 2 received open-label tocilizumab . Results In part 1 , 188 patients received tocilizumab  ( < 30 kg : 10 mg/kg ( n=35 ) or 8 mg/kg ( n=34 ) ; ≥30 kg : n=119 ) . In part 2 , 163 patients  received tocilizumab ( n=82 ) or placebo ( n=81 ) . JIA flare occurred in 48.1 % of patients on placebo versus 25.6 % continuing tocilizumab ( difference in means adjusted for stratification : −0.21 ; 95 % CI −0.35 to −0.08 ; p=0.0024 ) . At the end of part 2 , 64.6 % and 45.1 % of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses , respectively . Rates/100 patient-years ( PY ) of adverse events ( AEs ) and serious AEs ( SAEs ) were 480 and 12.5 , respectively ; infections were the most common SAE ( 4.9/100 PY ) . Conclusions Tocilizumab treatment results in significant improvement , maintained over time , of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis . Trial registration number : NCT00988221 Objective To investigate the efficacy and safety of etanercept ( ETN ) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods CLIPPER is an ongoing , Phase 3b , open-label , multicentre study ; the 12-week ( Part 1 ) data are reported here . Subjects with eoJIA ( 2–17 years ) , ERA ( 12–17 years ) , or PsA ( 12–17 years ) received ETN 0.8 mg/kg once weekly ( maximum 50 mg ) . Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology ( ACR ) 30 criteria at week 12 ; secondary outcomes included JIA ACR 50/70/90 and inactive disease . Results 122/127 ( 96.1 % ) subjects completed the study ( mean age 11.7 years ) . JIA ACR 30 ( 95 % CI ) was achieved by 88.6 % ( 81.6 % to 93.6 % ) of subjects overall ; 89.7 % ( 78.8 % to 96.1 % ) with eoJIA , 83.3 % ( 67.2 % to 93.6 % ) with ERA and 93.1 % ( 77.2 % to 99.2 % ) with PsA. For eoJIA , ERA , or PsA categories , the ORs of ETN vs the historical placebo data were 26.2 , 15.1 and 40.7 , respectively . Overall JIA ACR 50 , 70 , 90 and inactive disease were achieved by 81.1 , 61.5 , 29.8 and 12.1 % , respectively . Treatment-emergent adverse events ( AEs ) , infections , and serious AEs , were reported in 45 ( 35.4 % ) , 58 ( 45.7 % ) , and 4 ( 3.1 % ) , subjects , respectively . Serious AEs were one case each of abdominal pain , bronchopneumonia , gastroenteritis and pyelocystitis . One subject reported herpes zoster and another varicella . No differences in safety were observed across the JIA categories . Conclusions ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA , ERA and PsA , with no unexpected safety findings Introduction While adalimumab is licensed for ankylosing spondylitis ( AS ) , open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS ( JoAS ) . Methods A total of 32 patients aged 12 to 17 years with severe , active and refractory JoAS were enrolled in a multicenter , r and omized , double-blind , placebo-controlled parallel study of 12 weeks , followed by open-label adalimumab until week 24 for all patients . ASAS40 was used as the primary , and ASAS20 , PedACR and single items were used as the secondary outcome measures for the intention to treat population . Results A total of 17 patients were r and omized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo .  Two patients ( one of each group ) discontinued prematurely due to insufficient efficacy and were labeled as non-responders . In the double-blind part , more patients on adalimumab achieved an ASAS40 at week 4 ( 41 % ) , week 8 ( 53 % ) and week 12 ( 53 % ) than on placebo ( 20 % , 33 % , 33 % ) , while differences at week 8 only reached borderline significance ( P = 0.05 ) . Also , at 4 , 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group ( 53%/53%/29 % ; 59%/76%/41 % ; 53%/65%/53 % ) compared to placebo ( 27%/27%/7 % ; 27%/33%/13 % ; 33%/40%/27 % ) . In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24 . At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65 % ( P < 0.001 ) , the back pain score decreased by 50 % ( P < 0.005 ) , the Bath AS Functional Index ( BASFI ) score decreased by 47 % ( P < 0.02 ) , while the Childhood Health Assessment Question naire-Disability Index ( CHAQ-DI ) score improved by 65 % ( P < 0.005 ) . ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity , parents ' global assessment of subject 's overall well-being , active joint count ( all P < 0.05 ) and erythrocyte sedimentation rate ( ESR ) ( P < 0.01).During the 12-week controlled phase , 29 AEs occurred in 10 patients on placebo compared to 27 AEs in 11 patients on adalimumab . Injection site reactions were the most common adverse events . There were 17 various infections occurring in the double-blind phase , 8 on placebo , 9 on adalimumab and a further 19 in the open label period . Conclusions Adalimumab was well tolerated and highly effective in a double-blind r and omized trial in patients with JoAS . Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment . Trial registration EudraCT 2007 - 003358 - 27 Importance One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α ( TNF-α ) inhibitors ; little guidance on choosing the next treatment exists . Objective To compare the efficacy of a non-TNF-targeted biologic ( non-TNF ) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor . Design , Setting , and Participants A total of 300 patients ( conducted between 2009 - 2012 ) with rheumatoid arthritis , with persistent disease activity ( disease activity score in 28 joints-erythrocyte sedimentation rate [ DAS28-ESR ] ≥ 3.2 [ range , 0 - 9.3 ] ) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter , pragmatic , open-label r and omized clinical trial . The final follow-up date was in August 2013 . Interventions Patients were r and omly assigned ( 1:1 ) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment . The choice of the biologic prescribed within each r and omized group was left to the treating clinician . Main Outcomes and Measures The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism ( EULAR ) scale at week 24 . Secondary outcomes included the EULAR response at weeks 12 and 52 ; at weeks 12 , 24 , and 52 ; DAS28ESR , low disease activity ( DAS28 ≤3.2 ) , remission ( DAS28 ≤2.6 ) ; serious adverse events ; and serious infections . Results Of the 300 r and omized patients ( 243 [ 83.2 % ] women ; mean [ SD ] age , 57.1 [ 12.2 ] years ;  baseline DAS28-ESR , 5.1 [ 1.1 ] ) , 269 ( 89.7 % ) completed the study . At week 24 , 101 of 146 patients ( 69 % ) in the non-TNF group and 76 ( 52 % ) in the second anti-TNF group achieved a good or moderate EULAR response ( OR , 2.06 ; 95 % CI , 1.27 - 3.37 ; P = .004 , with imputation of missing data ; absolute difference , 17.2 % ; 95 % CI , 6.2 % to 28.2 % ) . The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group ( mean difference adjusted for baseline differences , -0.43 ; 95 % CI , -0.72 to -0.14 ; P = .004 ) . At weeks 24 and 52 , more patients in the non-TNF group vs the second anti-TNF group showed low disease activity ( 45 % vs 28 % at week 24 ; OR , 2.09 ; 95 % CI , 1.27 to 3.43 ; P = .004 and 41 % vs 23 % at week 52 ; OR , 2.26 ; 95 % CI , 1.33 to 3.86 ; P = .003 ) . Conclusions and Relevance Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response , a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication . Trial Registration clinical trials.gov Identifier : NCT01000441 To assess health‐related quality of life ( HRQOL ) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis ( JIA ) Objective . The main objective was to determine the 2-year clinical benefit and safety of  etanercept ( ETN ) in children with the juvenile idiopathic arthritis ( JIA ) categories of extended oligoarthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods . CLIPPER was a 96-week , phase IIIb , open-label , multicenter study . Patients with eoJIA , ERA , or PsA received ETN 0.8 mg/kg once weekly ( 50 mg max ) for up to 96 weeks . The proportions of patients reaching the JIA American College of Rheumatology ( ACR ) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated . Adverse events ( AE ) were collected throughout the study ( intention-to-treat sample ) . Results . There were 127 patients ( eoJIA n = 60 , ERA n = 38 , PsA n = 29 ) who received ≥ 1 dose of ETN .  The mean disease duration was 31.6 ( eoJIA ) , 23.0 ( ERA ) , and 21.8 ( PsA ) months . At Week 96 , JIA ACR  
    Output:
    
agent
Good disease control , with therapeutic escalation to achieve low disease activity , was recommended .
***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 evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis ( pcJIA ) . Methods This three-part , r and omised , placebo-controlled , double-blind withdrawal study ( NCT00988221 ) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate .  During part 1 , patients received open-label tocilizumab every 4 weeks ( 8 or 10 mg/kg for body weight ( BW ) < 30 kg ; 8 mg/kg for BW ≥30 kg ) . At week 16 , patients with ≥JIA-American College of Rheumatology ( ACR ) 30 improvement entered the 24-week , double-blind part 2 after r and omisation 1:1 to placebo or tocilizumab ( stratified by methotrexate and steroid background therapy ) for evaluation of the primary end point : JIA flare , compared with week 16 . Patients flaring or completing part 2 received open-label tocilizumab . Results In part 1 , 188 patients received tocilizumab  ( < 30 kg : 10 mg/kg ( n=35 ) or 8 mg/kg ( n=34 ) ; ≥30 kg : n=119 ) . In part 2 , 163 patients  received tocilizumab ( n=82 ) or placebo ( n=81 ) . JIA flare occurred in 48.1 % of patients on placebo versus 25.6 % continuing tocilizumab ( difference in means adjusted for stratification : −0.21 ; 95 % CI −0.35 to −0.08 ; p=0.0024 ) . At the end of part 2 , 64.6 % and 45.1 % of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses , respectively . Rates/100 patient-years ( PY ) of adverse events ( AEs ) and serious AEs ( SAEs ) were 480 and 12.5 , respectively ; infections were the most common SAE ( 4.9/100 PY ) . Conclusions Tocilizumab treatment results in significant improvement , maintained over time , of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis . Trial registration number : NCT00988221 Objective To investigate the efficacy and safety of etanercept ( ETN ) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods CLIPPER is an ongoing , Phase 3b , open-label , multicentre study ; the 12-week ( Part 1 ) data are reported here . Subjects with eoJIA ( 2–17 years ) , ERA ( 12–17 years ) , or PsA ( 12–17 years ) received ETN 0.8 mg/kg once weekly ( maximum 50 mg ) . Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology ( ACR ) 30 criteria at week 12 ; secondary outcomes included JIA ACR 50/70/90 and inactive disease . Results 122/127 ( 96.1 % ) subjects completed the study ( mean age 11.7 years ) . JIA ACR 30 ( 95 % CI ) was achieved by 88.6 % ( 81.6 % to 93.6 % ) of subjects overall ; 89.7 % ( 78.8 % to 96.1 % ) with eoJIA , 83.3 % ( 67.2 % to 93.6 % ) with ERA and 93.1 % ( 77.2 % to 99.2 % ) with PsA. For eoJIA , ERA , or PsA categories , the ORs of ETN vs the historical placebo data were 26.2 , 15.1 and 40.7 , respectively . Overall JIA ACR 50 , 70 , 90 and inactive disease were achieved by 81.1 , 61.5 , 29.8 and 12.1 % , respectively . Treatment-emergent adverse events ( AEs ) , infections , and serious AEs , were reported in 45 ( 35.4 % ) , 58 ( 45.7 % ) , and 4 ( 3.1 % ) , subjects , respectively . Serious AEs were one case each of abdominal pain , bronchopneumonia , gastroenteritis and pyelocystitis . One subject reported herpes zoster and another varicella . No differences in safety were observed across the JIA categories . Conclusions ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA , ERA and PsA , with no unexpected safety findings Introduction While adalimumab is licensed for ankylosing spondylitis ( AS ) , open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS ( JoAS ) . Methods A total of 32 patients aged 12 to 17 years with severe , active and refractory JoAS were enrolled in a multicenter , r and omized , double-blind , placebo-controlled parallel study of 12 weeks , followed by open-label adalimumab until week 24 for all patients . ASAS40 was used as the primary , and ASAS20 , PedACR and single items were used as the secondary outcome measures for the intention to treat population . Results A total of 17 patients were r and omized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo .  Two patients ( one of each group ) discontinued prematurely due to insufficient efficacy and were labeled as non-responders . In the double-blind part , more patients on adalimumab achieved an ASAS40 at week 4 ( 41 % ) , week 8 ( 53 % ) and week 12 ( 53 % ) than on placebo ( 20 % , 33 % , 33 % ) , while differences at week 8 only reached borderline significance ( P = 0.05 ) . Also , at 4 , 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group ( 53%/53%/29 % ; 59%/76%/41 % ; 53%/65%/53 % ) compared to placebo ( 27%/27%/7 % ; 27%/33%/13 % ; 33%/40%/27 % ) . In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24 . At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65 % ( P < 0.001 ) , the back pain score decreased by 50 % ( P < 0.005 ) , the Bath AS Functional Index ( BASFI ) score decreased by 47 % ( P < 0.02 ) , while the Childhood Health Assessment Question naire-Disability Index ( CHAQ-DI ) score improved by 65 % ( P < 0.005 ) . ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity , parents ' global assessment of subject 's overall well-being , active joint count ( all P < 0.05 ) and erythrocyte sedimentation rate ( ESR ) ( P < 0.01).During the 12-week controlled phase , 29 AEs occurred in 10 patients on placebo compared to 27 AEs in 11 patients on adalimumab . Injection site reactions were the most common adverse events . There were 17 various infections occurring in the double-blind phase , 8 on placebo , 9 on adalimumab and a further 19 in the open label period . Conclusions Adalimumab was well tolerated and highly effective in a double-blind r and omized trial in patients with JoAS . Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment . Trial registration EudraCT 2007 - 003358 - 27 Importance One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α ( TNF-α ) inhibitors ; little guidance on choosing the next treatment exists . Objective To compare the efficacy of a non-TNF-targeted biologic ( non-TNF ) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor . Design , Setting , and Participants A total of 300 patients ( conducted between 2009 - 2012 ) with rheumatoid arthritis , with persistent disease activity ( disease activity score in 28 joints-erythrocyte sedimentation rate [ DAS28-ESR ] ≥ 3.2 [ range , 0 - 9.3 ] ) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter , pragmatic , open-label r and omized clinical trial . The final follow-up date was in August 2013 . Interventions Patients were r and omly assigned ( 1:1 ) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment . The choice of the biologic prescribed within each r and omized group was left to the treating clinician . Main Outcomes and Measures The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism ( EULAR ) scale at week 24 . Secondary outcomes included the EULAR response at weeks 12 and 52 ; at weeks 12 , 24 , and 52 ; DAS28ESR , low disease activity ( DAS28 ≤3.2 ) , remission ( DAS28 ≤2.6 ) ; serious adverse events ; and serious infections . Results Of the 300 r and omized patients ( 243 [ 83.2 % ] women ; mean [ SD ] age , 57.1 [ 12.2 ] years ;  baseline DAS28-ESR , 5.1 [ 1.1 ] ) , 269 ( 89.7 % ) completed the study . At week 24 , 101 of 146 patients ( 69 % ) in the non-TNF group and 76 ( 52 % ) in the second anti-TNF group achieved a good or moderate EULAR response ( OR , 2.06 ; 95 % CI , 1.27 - 3.37 ; P = .004 , with imputation of missing data ; absolute difference , 17.2 % ; 95 % CI , 6.2 % to 28.2 % ) . The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group ( mean difference adjusted for baseline differences , -0.43 ; 95 % CI , -0.72 to -0.14 ; P = .004 ) . At weeks 24 and 52 , more patients in the non-TNF group vs the second anti-TNF group showed low disease activity ( 45 % vs 28 % at week 24 ; OR , 2.09 ; 95 % CI , 1.27 to 3.43 ; P = .004 and 41 % vs 23 % at week 52 ; OR , 2.26 ; 95 % CI , 1.33 to 3.86 ; P = .003 ) . Conclusions and Relevance Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response , a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication . Trial Registration clinical trials.gov Identifier : NCT01000441 To assess health‐related quality of life ( HRQOL ) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis ( JIA ) Objective . The main objective was to determine the 2-year clinical benefit and safety of  etanercept ( ETN ) in children with the juvenile idiopathic arthritis ( JIA ) categories of extended oligoarthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods . CLIPPER was a 96-week , phase IIIb , open-label , multicenter study . Patients with eoJIA , ERA , or PsA received ETN 0.8 mg/kg once weekly ( 50 mg max ) for up to 96 weeks . The proportions of patients reaching the JIA American College of Rheumatology ( ACR ) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated . Adverse events ( AE ) were collected throughout the study ( intention-to-treat sample ) . Results . There were 127 patients ( eoJIA n = 60 , ERA n = 38 , PsA n = 29 ) who received ≥ 1 dose of ETN .  The mean disease duration was 31.6 ( eoJIA ) , 23.0 ( ERA ) , and 21.8 ( PsA ) months . At Week 96 , JIA ACR  
    Output:
    