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: The objective of this study was to evaluate the efficacy , pharmacokinetics , and safety of adalimumab in patients with polyarticular juvenile idiopathic arthritis ( JIA ) in Japan . Patients aged 4 to 17 years were enrolled in a single-arm , open-label , multicentre study of adalimumab .  Patients weighing < 30 kg received 20 mg every other week ( eow ) , and those ≥30 kg received 40 mg eow . Concomitant methotrexate ( MTX ) was allowed ( ≤10 mg/m2 per week ) . The primary efficacy outcome was the percent of patients with American College of Rheumatology Pediatric 30 response  ( ACR Pedi 30 ) at week 16 . JIA core variables , serum adalimumab concentrations , and anti-adalimumab antibodies ( AAAs ) were analysed . Patients were monitored for adverse events ( AEs ) . Twenty-five patients ( 20 with concomitant MTX at baseline and 5 without ) were enrolled : 24 patients completed 16 weeks of therapy and 22 patients completed 60 weeks . At week 16 , 90 % of patients with MTX and 100 % without MTX  achieved ACR Pedi 30 ; response rates were maintained through week 60 in 94 and 80 % of patients , respectively . Each JIA core variable improved over time . Six patients became AAA positive ( two each at weeks 8 , 16 , and 60 ) , some of which were transient . All six AAA-positive patients achieved ACR Pedi 30 at week 16 , and four maintained that response at week 60 . Six patients ( all with MTX ) experienced nine serious AEs ( JIA , pyrexia , arthralgia , pneumonia , hepatitis B infection , pharyngitis , dehydration , pharyngeal pain , and pneumonia ) . In pediatric patients with polyarticular JIA in Japan , adalimumab was safe and effective for reducing disease activity for up to 60 weeks 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 determine the long-term safety and efficacy of rilonacept , an anti-interleukin-1 fusion protein , in patients with active systemic juvenile idiopathic arthritis ( JIA ) . METHODS In patients with systemic JIA , ages 4 - 20 years , the efficacy of rilonacept was evaluated using 30 % , 50 % , and 70 % levels of improvement according to the adapted American College of Rheumatology ( ACR ) Pediatric 30 , 50 , and 70 response criteria , respectively . Efficacy and safety were evaluated during 23 months of open-label treatment ( 3 phases ) after a 4-week , double-blind , placebo-controlled phase . Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept , patients were eligible to receive open-label treatment at their prior dose , with adjustments . Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity ( i.e. , decreased levels of D-dimer and myeloid-related proteins [ MRPs ] ) were also evaluated . RESULTS Twenty-four patients entered the double-blind study and 23 entered the open-label period . Patients were predominantly white and female , and had a median age of 14.0 years at baseline . No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase , but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur . Adapted ACR Pediatric 30 , 50 , and 70 response rates at 3 months from the start of the study were 78.3 % , 60.9 % , and 34.8 % , respectively ; these responses were generally maintained over the study duration . Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study , and in 22 of 23 patients , the prednisone dose was decreased or prednisone therapy was discontinued . No serious treatment-related adverse events were observed . CONCLUSION Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in > 50 % of rilonacept-treated patients over 2 years . Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated Adalimumab is a TNF-α blocker antibody similar in structure and function to natural human IgG1 . Even if adalimumab is fully humanized , the development of anti-drug antibodies has been reported in several inflammatory conditions . The objective of our study was to assess the presence of  anti-adalimumab antibodies ( AAA ) and their clinical relevance in a cohort of juvenile idiopathic arthritis ( JIA ) patients on adalimumab . This is a prospect i ve observational cohort study recruiting JIA children . Experiments were performed using a vali date d surface plasmon resonance (SPR)-based optical assay ( Biacore ® T100 ) . Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score with 10 joint count ( JADAS-10 ) . The Mann – Whitney U test , Wilcoxon signed-rank test for paired sample s , chi-square , and Fisher exact test were used to compare data . Pearson ’s and Spearman ’s correlation tests were used to determine correlation coefficients for entered variables : demographic , clinical , and serological data . Ten ( 37 % ) out of 27 patients included in the study had at least one AAA-positive sample . Patients developed AAA between 3 and 38 months after starting adalimumab . Seven ( 70 % ) out of 10 children with AAA positivity experienced at least a relapse compared to 4 ( 23.5 % ) out of 17 AAA-negative children ( rs 0.45 , p < 0.017 ) . In conclusion , using an innovative and accurate assay method , we found a high incidence of anti-drug antibodies in a cohort of adalimumab-treated JIA patients observed over a mean period of 40 weeks ; the presence of anti-adalimumab antibodies seemed to be related to the number of relapses BACKGROUND We evaluated the safety and efficacy of etanercept , a soluble tumor necrosis factor receptor (p75):Fc fusion protein , in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate . METHODS Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial , open-label part of a multicenter trial . Those who responded to treatment then entered a double-blind study and were r and omly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred . A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity , with no more than one indicator worsening by more than 30 percent . RESULTS At the end of the open-label study , 51 of the 69 patients ( 74 percent ) had had responses to etanercept treatment . In the double-blind study , 21 of the 26 patients who received placebo ( 81 percent ) withdrew because of disease flare , as compared with 7 of the 25 patients who received etanercept ( 28 percent ) ( P=0.003 ) . The median time to disease flare with placebo was 28 days , as compared with more than 116 days with etanercept ( P<0.001 ) . In the double-blind study , there were no significant differences between the two treatment groups in the frequency of adverse events . CONCLUSIONS Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis .  Etanercept is well tolerated by pediatric patients 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 30/50/70/90/100/inactive disease responses ( 95 % CI ) were achieved by 84.3 % ( 76.7 , 90.1 ) , 83.5 % ( 75.8 , 89.5 ) , 78.7 % ( 70.6 , 85.5 ) , 55.1 % ( 46.0 , 63.9 ) , 45.7 % ( 36.8 , 54.7 ) , and 27.6 % ( 20.0 , 36.2 ) of patients , respectively . The most common AE ( no. events , events per 100 patient-yrs ) overall were headache ( 23 , 10.7 ) , pyrexia ( 12 , 5.6 ) , and diarrhea ( 10 , 4.6 ) . The most common infections were upper respiratory tract infection ( 83 , 38.6 ) , pharyngitis ( 50 , 23.2 ) , gastroenteritis ( 22 , 10.2 ) , bronchitis ( 19 , 8.8 ) , and rhinitis ( 17 , 7.9 ) . No cases of malignancy , active tuberculosis , demyelinating disorders , or death were reported . Conclusion . Over 96 weeks of therapy , ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories , with no major safety issues The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis ( JIA ) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period , a 6‐month double‐blind withdrawal period , and a long‐term extension ( LTE ) phase . The 
    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: The objective of this study was to evaluate the efficacy , pharmacokinetics , and safety of adalimumab in patients with polyarticular juvenile idiopathic arthritis ( JIA ) in Japan . Patients aged 4 to 17 years were enrolled in a single-arm , open-label , multicentre study of adalimumab .  Patients weighing < 30 kg received 20 mg every other week ( eow ) , and those ≥30 kg received 40 mg eow . Concomitant methotrexate ( MTX ) was allowed ( ≤10 mg/m2 per week ) . The primary efficacy outcome was the percent of patients with American College of Rheumatology Pediatric 30 response  ( ACR Pedi 30 ) at week 16 . JIA core variables , serum adalimumab concentrations , and anti-adalimumab antibodies ( AAAs ) were analysed . Patients were monitored for adverse events ( AEs ) . Twenty-five patients ( 20 with concomitant MTX at baseline and 5 without ) were enrolled : 24 patients completed 16 weeks of therapy and 22 patients completed 60 weeks . At week 16 , 90 % of patients with MTX and 100 % without MTX  achieved ACR Pedi 30 ; response rates were maintained through week 60 in 94 and 80 % of patients , respectively . Each JIA core variable improved over time . Six patients became AAA positive ( two each at weeks 8 , 16 , and 60 ) , some of which were transient . All six AAA-positive patients achieved ACR Pedi 30 at week 16 , and four maintained that response at week 60 . Six patients ( all with MTX ) experienced nine serious AEs ( JIA , pyrexia , arthralgia , pneumonia , hepatitis B infection , pharyngitis , dehydration , pharyngeal pain , and pneumonia ) . In pediatric patients with polyarticular JIA in Japan , adalimumab was safe and effective for reducing disease activity for up to 60 weeks 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 determine the long-term safety and efficacy of rilonacept , an anti-interleukin-1 fusion protein , in patients with active systemic juvenile idiopathic arthritis ( JIA ) . METHODS In patients with systemic JIA , ages 4 - 20 years , the efficacy of rilonacept was evaluated using 30 % , 50 % , and 70 % levels of improvement according to the adapted American College of Rheumatology ( ACR ) Pediatric 30 , 50 , and 70 response criteria , respectively . Efficacy and safety were evaluated during 23 months of open-label treatment ( 3 phases ) after a 4-week , double-blind , placebo-controlled phase . Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept , patients were eligible to receive open-label treatment at their prior dose , with adjustments . Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity ( i.e. , decreased levels of D-dimer and myeloid-related proteins [ MRPs ] ) were also evaluated . RESULTS Twenty-four patients entered the double-blind study and 23 entered the open-label period . Patients were predominantly white and female , and had a median age of 14.0 years at baseline . No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase , but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur . Adapted ACR Pediatric 30 , 50 , and 70 response rates at 3 months from the start of the study were 78.3 % , 60.9 % , and 34.8 % , respectively ; these responses were generally maintained over the study duration . Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study , and in 22 of 23 patients , the prednisone dose was decreased or prednisone therapy was discontinued . No serious treatment-related adverse events were observed . CONCLUSION Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in > 50 % of rilonacept-treated patients over 2 years . Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated Adalimumab is a TNF-α blocker antibody similar in structure and function to natural human IgG1 . Even if adalimumab is fully humanized , the development of anti-drug antibodies has been reported in several inflammatory conditions . The objective of our study was to assess the presence of  anti-adalimumab antibodies ( AAA ) and their clinical relevance in a cohort of juvenile idiopathic arthritis ( JIA ) patients on adalimumab . This is a prospect i ve observational cohort study recruiting JIA children . Experiments were performed using a vali date d surface plasmon resonance (SPR)-based optical assay ( Biacore ® T100 ) . Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score with 10 joint count ( JADAS-10 ) . The Mann – Whitney U test , Wilcoxon signed-rank test for paired sample s , chi-square , and Fisher exact test were used to compare data . Pearson ’s and Spearman ’s correlation tests were used to determine correlation coefficients for entered variables : demographic , clinical , and serological data . Ten ( 37 % ) out of 27 patients included in the study had at least one AAA-positive sample . Patients developed AAA between 3 and 38 months after starting adalimumab . Seven ( 70 % ) out of 10 children with AAA positivity experienced at least a relapse compared to 4 ( 23.5 % ) out of 17 AAA-negative children ( rs 0.45 , p < 0.017 ) . In conclusion , using an innovative and accurate assay method , we found a high incidence of anti-drug antibodies in a cohort of adalimumab-treated JIA patients observed over a mean period of 40 weeks ; the presence of anti-adalimumab antibodies seemed to be related to the number of relapses BACKGROUND We evaluated the safety and efficacy of etanercept , a soluble tumor necrosis factor receptor (p75):Fc fusion protein , in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate . METHODS Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial , open-label part of a multicenter trial . Those who responded to treatment then entered a double-blind study and were r and omly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred . A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity , with no more than one indicator worsening by more than 30 percent . RESULTS At the end of the open-label study , 51 of the 69 patients ( 74 percent ) had had responses to etanercept treatment . In the double-blind study , 21 of the 26 patients who received placebo ( 81 percent ) withdrew because of disease flare , as compared with 7 of the 25 patients who received etanercept ( 28 percent ) ( P=0.003 ) . The median time to disease flare with placebo was 28 days , as compared with more than 116 days with etanercept ( P<0.001 ) . In the double-blind study , there were no significant differences between the two treatment groups in the frequency of adverse events . CONCLUSIONS Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis .  Etanercept is well tolerated by pediatric patients 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 30/50/70/90/100/inactive disease responses ( 95 % CI ) were achieved by 84.3 % ( 76.7 , 90.1 ) , 83.5 % ( 75.8 , 89.5 ) , 78.7 % ( 70.6 , 85.5 ) , 55.1 % ( 46.0 , 63.9 ) , 45.7 % ( 36.8 , 54.7 ) , and 27.6 % ( 20.0 , 36.2 ) of patients , respectively . The most common AE ( no. events , events per 100 patient-yrs ) overall were headache ( 23 , 10.7 ) , pyrexia ( 12 , 5.6 ) , and diarrhea ( 10 , 4.6 ) . The most common infections were upper respiratory tract infection ( 83 , 38.6 ) , pharyngitis ( 50 , 23.2 ) , gastroenteritis ( 22 , 10.2 ) , bronchitis ( 19 , 8.8 ) , and rhinitis ( 17 , 7.9 ) . No cases of malignancy , active tuberculosis , demyelinating disorders , or death were reported . Conclusion . Over 96 weeks of therapy , ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories , with no major safety issues The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis ( JIA ) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period , a 6‐month double‐blind withdrawal period , and a long‐term extension ( LTE ) phase . The 
    Output:
    