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 : Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor . Objective : To evaluate the efficacy and safety of certolizumab pegol versus placebo , plus methotrexate ( MTX ) , in patients with active rheumatoid arthritis ( RA ) . Methods : An international , multicentre , phase 3 , r and omised , double-blind , placebo-controlled study in active adult-onset RA . Patients ( n = 619 ) were r and omised 2:2:1 to subcutaneous certolizumab pegol ( liquid formulation ) 400 mg at weeks 0 , 2 and 4 followed by 200 mg or 400 mg plus MTX , or placebo plus MTX , every 2 weeks for 24 weeks . The primary end point was ACR20 response at week 24 . Secondary end points included ACR50 and ACR70 responses , change from baseline in modified Total Sharp Score , ACR core set variables and physical function . Results : Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response  versus placebo ( p⩽0.001 ) ; rates were 57.3 % , 57.6 % and 8.7 % , respectively . Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression ; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4 , respectively , versus 1.2 for placebo ( rank analysis p⩽0.01 ) . Certolizumab pegol-treated patients reported rapid and significant improvements in physical function  versus placebo ; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50 , respectively , versus −0.14 for placebo ( p⩽0.001 ) . Most adverse events were mild or moderate , with low incidence of withdrawals due to adverse events . Five patients developed tuberculosis . Conclusion : Certolizumab pegol plus MTX was more efficacious than placebo plus MTX , rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression . Trial registration number : Objective : To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis ( RA ) despite sulfasalazine therapy . Methods : Patients were r and omly assigned to etanercept ( 25 mg twice weekly ; sulfasalazine was discontinued at baseline ) , etanercept plus sulfasalazine ( unchanged regimen of 2–3 g/day ) or sulfasalazine in a double-blind , r and omised , 2-year study in adult patients with active RA despite sulfasalazine therapy .  Efficacy was assessed using the American College of Rheumatology criteria , disease activity scores ( DAS ) and patient-reported outcomes ( PRO ) . Results : Demographic variables and baseline disease characteristics were comparable among treatment groups ; mean DAS 5.1 , 5.2 and 5.1 for etanercept ( n = 103 ) , etanercept plus sulfasalazine ( n = 101 ) and sulfasalazine ( n = 50 ) , respectively . Withdrawal due to lack of efficacy was highest with sulfasalazine ( 26 ( 52 % ) vs 6 ( 6 % ) for either etanercept group , p<0.001 ) . Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response , which was sustained at 2 years , than those receiving sulfasalazine : mean DAS 2.8 , 2.5 versus 4.5 , respectively ( p<0.05 ) ; ACR 20 response was achieved by 67 % , 77 % versus 34 % of patients , respectively ( p<0.01 ) Overall , PRO followed a similar pattern ; a clinical ly significant improvement in health assessment question naire was achieved by 76 % , 78 % versus 40 % of patients , respectively ( p<0.01 ) . Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis ( p<0.01 ) . Conclusion : Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA . The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine Objective : To compare patient reported measures of function , health related quality of life ( QoL ) , and satisfaction with medication among patients with rheumatoid arthritis ( RA ) treated with methotrexate ( MTX ) , etanercept , or both for up to 1 year . Methods : In a 52 week , double blind , clinical trial , patients with active RA were r and omised to receive etanercept 25 mg twice weekly , methotrexate up to 20 mg weekly , or combination therapy .  The Health Assessment Question naire ( HAQ ) disability index , EuroQoL health status visual analogue scale ( EQ-5D VAS ) , patient global assessment , and patient general health VAS were administered at baseline and weeks 2 , 4 , 8 , 12 , 16 , 20 , 24 , 32 , 40 , 48 , and 52 . Satisfaction with the medication was compared at 52 weeks . Results : Of 682 enrolled patients , 522 completed 52 weeks of treatment . Mean improvement from baseline in HAQ score was 0.65 , 0.70 , and 1.0 for MTX , etanercept , and the combination , respectively . The mean percentage and absolute improvement in the HAQ was significantly higher ( p<0.01 ) for combination therapy than for either of the monotherapies . Combination therapy produced significantly more rapid achievement of HAQ ⩽0.5 sustained for 6 months than either of the monotherapies ( p<0.01 ) . Compared with patients receiving monotherapy , those receiving combination therapy achieved a significantly better ( p<0.05 ) health state as measured by the EQ-5D VAS ( mean ( SD ) 63.7 ( 3.2 ) , 66.8 ( 3.2 ) , 72.7 ( 3.1 ) for MTX , etanercept , and the combination , respectively ) . Results were similar for other assessment s ( p<0.01 ) . Patients in combination and etanercept groups were significantly more likely ( p<0.0001 , p = 0.0009 , respectively ) to report satisfaction with the medication . Conclusions : Combination therapy with etanercept and methotrexate improved function , QoL , and satisfaction with the medication significantly more than monotherapy Objective : The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis ( RA ) despite methotrexate therapy . Methods : Patients were r and omly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules ( group 1 , n = 133 ) , golimumab 100 mg injections plus placebo capsules ( group 2 , n = 133 ) , golimumab 50 mg injections plus methotrexate capsules ( group 3 , n = 89 ) , or golimumab 100 mg injections plus methotrexate capsules ( group 4 , n = 89 ) . Injections were administered subcutaneously every 4 weeks . The co- primary endpoints were the proportion of patients with 20 % or greater improvement in the American College of Rheumatology criteria ( ACR20 ) at week 14 and the change from baseline in the health assessment question naire-disability index ( HAQ-DI ) score at week 24 . Results : The proportion of patients who achieved an ACR20 response at week 14 was 33.1 % in the placebo plus methotrexate group , 44.4 % ( p = 0.059 ) in the golimumab 100 mg plus placebo group , 55.1 % ( p = 0.001 ) in the golimumab 50 mg plus methotrexate group and 56.2 % ( p<0.001 ) in the golimumab 100 mg plus methotrexate group . At week 24 , median improvements from baseline in HAQ-DI scores were 0.13 , 0.13 ( p = 0.240 ) , 0.38 ( p<0.001 ) and 0.50 ( p<0.001 ) , respectively . During the placebo-controlled portion of the study ( to week 16 ) , serious adverse events occurred in 2.3 % , 3.8 % , 5.6 % and 9.0 % of patients and serious infections occurred in 0.8 % , 0.8 % , 2.2 % and 5.6 % , respectively . Conclusion : The addition of golimumab to methotrexate  in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function Introduction The objective of this study was to assess the impact of certolizumab pegol ( CZP ) treatment on health-related quality of life ( HRQoL ) , fatigue and other patient-reported outcomes ( PROs ) in patients with rheumatoid arthritis ( RA ) . Methods Patients with active RA ( N = 982 ) were r and omized 2:2:1 to subcutaneous CZP  ( 400 mg at weeks 0 , 2 and 4 ; followed by CZP 200 mg or 400 mg ) plus methotrexate ( MTX ) every other week , or placebo ( PBO ) plus MTX . PRO assessment s included HRQoL , fatigue , physical function , arthritis pain and disease activity . Adjusted mean changes from baseline in all PROs were obtained using analysis of covariance ( ANCOVA ) applying last observation carried forward ( LOCF ) imputation . The proportion of patients achieving clinical ly meaningful improvements in each PRO was obtained using logistic regression and by applying non-responder imputation to missing values after rescue medication or withdrawal . The correlations between PRO responses and clinical responses were also assessed by tetrachoric correlation using non-responder imputation . Results Patients treated with CZP plus MTX reported significant ( P < 0.001 ) , clinical ly meaningful improvements in HRQoL at the first assessment ( week 12 ) ; reductions in fatigue , disease activity and pain and improvements in physical function were reported at week 1 . In particular , CZP-treated patients reported improvements in mental health . Mean changes from baseline in the SF-36 Mental Component Summary ( MCS ) at week 52 for CZP 200 mg and 400 mg plus MTX , and PBO plus MTX were 6.4 , 6.4 and 2.1 , respectively ( P < 0.001 ) . In addition , mental health and vitality scores in CZP-treated patients approached age- and gender-adjusted US population norms . Improvements in all PROs were sustained . Similar benefits were reported with both CZP doses . Changes in SF-36 MCS scores had the lowest correlation with disease activity scores ( DAS28 ) and American College of Rheumatology 20 % improvement ( ACR20 ) response rates , while improvements in pain showed the highest correlation . Conclusions Treatment with CZP plus MTX result ed in rapid and sustained improvements in all PROs , indicating that the benefits of CZP extend beyond clinical efficacy endpoints into areas that are more relevant and meaningful for patients on a daily basis . Trial Registration Clinical Trials.gov NCT00152386 BACKGROUND Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses . Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis . METHODS In this double-blind , r and omised , placebo-controlled , parallel group phase III study , 623 patients with moderate to severe active rheumatoid arthritis were r and omly assigned with an interactive voice response system , stratified by site with a r and omisation list provided by the study sponsor , to receive tocilizumab 8 mg/kg ( n=205 ) , tocilizumab 4 mg/kg ( 214 ) , or placebo ( 204 ) intravenously every 4 weeks , with methotrexate at stable pre- study doses ( 10 - 25 mg/week ) . Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20 % improvement in both swollen and tender joint counts . The primary endpoint was the proportion of patients with 20 % improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria ( ACR20 response ) at week 24 . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00106548 . FINDINGS The intention-to-treat analysis population consisted of 622 patients : one patient in the 4 mg/kg group did not receive study treatment and was thus excluded . At 24 weeks , ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo ( 120 [ 59 % ] patients in 
    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 : Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor . Objective : To evaluate the efficacy and safety of certolizumab pegol versus placebo , plus methotrexate ( MTX ) , in patients with active rheumatoid arthritis ( RA ) . Methods : An international , multicentre , phase 3 , r and omised , double-blind , placebo-controlled study in active adult-onset RA . Patients ( n = 619 ) were r and omised 2:2:1 to subcutaneous certolizumab pegol ( liquid formulation ) 400 mg at weeks 0 , 2 and 4 followed by 200 mg or 400 mg plus MTX , or placebo plus MTX , every 2 weeks for 24 weeks . The primary end point was ACR20 response at week 24 . Secondary end points included ACR50 and ACR70 responses , change from baseline in modified Total Sharp Score , ACR core set variables and physical function . Results : Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response  versus placebo ( p⩽0.001 ) ; rates were 57.3 % , 57.6 % and 8.7 % , respectively . Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression ; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4 , respectively , versus 1.2 for placebo ( rank analysis p⩽0.01 ) . Certolizumab pegol-treated patients reported rapid and significant improvements in physical function  versus placebo ; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50 , respectively , versus −0.14 for placebo ( p⩽0.001 ) . Most adverse events were mild or moderate , with low incidence of withdrawals due to adverse events . Five patients developed tuberculosis . Conclusion : Certolizumab pegol plus MTX was more efficacious than placebo plus MTX , rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression . Trial registration number : Objective : To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis ( RA ) despite sulfasalazine therapy . Methods : Patients were r and omly assigned to etanercept ( 25 mg twice weekly ; sulfasalazine was discontinued at baseline ) , etanercept plus sulfasalazine ( unchanged regimen of 2–3 g/day ) or sulfasalazine in a double-blind , r and omised , 2-year study in adult patients with active RA despite sulfasalazine therapy .  Efficacy was assessed using the American College of Rheumatology criteria , disease activity scores ( DAS ) and patient-reported outcomes ( PRO ) . Results : Demographic variables and baseline disease characteristics were comparable among treatment groups ; mean DAS 5.1 , 5.2 and 5.1 for etanercept ( n = 103 ) , etanercept plus sulfasalazine ( n = 101 ) and sulfasalazine ( n = 50 ) , respectively . Withdrawal due to lack of efficacy was highest with sulfasalazine ( 26 ( 52 % ) vs 6 ( 6 % ) for either etanercept group , p<0.001 ) . Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response , which was sustained at 2 years , than those receiving sulfasalazine : mean DAS 2.8 , 2.5 versus 4.5 , respectively ( p<0.05 ) ; ACR 20 response was achieved by 67 % , 77 % versus 34 % of patients , respectively ( p<0.01 ) Overall , PRO followed a similar pattern ; a clinical ly significant improvement in health assessment question naire was achieved by 76 % , 78 % versus 40 % of patients , respectively ( p<0.01 ) . Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis ( p<0.01 ) . Conclusion : Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA . The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine Objective : To compare patient reported measures of function , health related quality of life ( QoL ) , and satisfaction with medication among patients with rheumatoid arthritis ( RA ) treated with methotrexate ( MTX ) , etanercept , or both for up to 1 year . Methods : In a 52 week , double blind , clinical trial , patients with active RA were r and omised to receive etanercept 25 mg twice weekly , methotrexate up to 20 mg weekly , or combination therapy .  The Health Assessment Question naire ( HAQ ) disability index , EuroQoL health status visual analogue scale ( EQ-5D VAS ) , patient global assessment , and patient general health VAS were administered at baseline and weeks 2 , 4 , 8 , 12 , 16 , 20 , 24 , 32 , 40 , 48 , and 52 . Satisfaction with the medication was compared at 52 weeks . Results : Of 682 enrolled patients , 522 completed 52 weeks of treatment . Mean improvement from baseline in HAQ score was 0.65 , 0.70 , and 1.0 for MTX , etanercept , and the combination , respectively . The mean percentage and absolute improvement in the HAQ was significantly higher ( p<0.01 ) for combination therapy than for either of the monotherapies . Combination therapy produced significantly more rapid achievement of HAQ ⩽0.5 sustained for 6 months than either of the monotherapies ( p<0.01 ) . Compared with patients receiving monotherapy , those receiving combination therapy achieved a significantly better ( p<0.05 ) health state as measured by the EQ-5D VAS ( mean ( SD ) 63.7 ( 3.2 ) , 66.8 ( 3.2 ) , 72.7 ( 3.1 ) for MTX , etanercept , and the combination , respectively ) . Results were similar for other assessment s ( p<0.01 ) . Patients in combination and etanercept groups were significantly more likely ( p<0.0001 , p = 0.0009 , respectively ) to report satisfaction with the medication . Conclusions : Combination therapy with etanercept and methotrexate improved function , QoL , and satisfaction with the medication significantly more than monotherapy Objective : The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis ( RA ) despite methotrexate therapy . Methods : Patients were r and omly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules ( group 1 , n = 133 ) , golimumab 100 mg injections plus placebo capsules ( group 2 , n = 133 ) , golimumab 50 mg injections plus methotrexate capsules ( group 3 , n = 89 ) , or golimumab 100 mg injections plus methotrexate capsules ( group 4 , n = 89 ) . Injections were administered subcutaneously every 4 weeks . The co- primary endpoints were the proportion of patients with 20 % or greater improvement in the American College of Rheumatology criteria ( ACR20 ) at week 14 and the change from baseline in the health assessment question naire-disability index ( HAQ-DI ) score at week 24 . Results : The proportion of patients who achieved an ACR20 response at week 14 was 33.1 % in the placebo plus methotrexate group , 44.4 % ( p = 0.059 ) in the golimumab 100 mg plus placebo group , 55.1 % ( p = 0.001 ) in the golimumab 50 mg plus methotrexate group and 56.2 % ( p<0.001 ) in the golimumab 100 mg plus methotrexate group . At week 24 , median improvements from baseline in HAQ-DI scores were 0.13 , 0.13 ( p = 0.240 ) , 0.38 ( p<0.001 ) and 0.50 ( p<0.001 ) , respectively . During the placebo-controlled portion of the study ( to week 16 ) , serious adverse events occurred in 2.3 % , 3.8 % , 5.6 % and 9.0 % of patients and serious infections occurred in 0.8 % , 0.8 % , 2.2 % and 5.6 % , respectively . Conclusion : The addition of golimumab to methotrexate  in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function Introduction The objective of this study was to assess the impact of certolizumab pegol ( CZP ) treatment on health-related quality of life ( HRQoL ) , fatigue and other patient-reported outcomes ( PROs ) in patients with rheumatoid arthritis ( RA ) . Methods Patients with active RA ( N = 982 ) were r and omized 2:2:1 to subcutaneous CZP  ( 400 mg at weeks 0 , 2 and 4 ; followed by CZP 200 mg or 400 mg ) plus methotrexate ( MTX ) every other week , or placebo ( PBO ) plus MTX . PRO assessment s included HRQoL , fatigue , physical function , arthritis pain and disease activity . Adjusted mean changes from baseline in all PROs were obtained using analysis of covariance ( ANCOVA ) applying last observation carried forward ( LOCF ) imputation . The proportion of patients achieving clinical ly meaningful improvements in each PRO was obtained using logistic regression and by applying non-responder imputation to missing values after rescue medication or withdrawal . The correlations between PRO responses and clinical responses were also assessed by tetrachoric correlation using non-responder imputation . Results Patients treated with CZP plus MTX reported significant ( P < 0.001 ) , clinical ly meaningful improvements in HRQoL at the first assessment ( week 12 ) ; reductions in fatigue , disease activity and pain and improvements in physical function were reported at week 1 . In particular , CZP-treated patients reported improvements in mental health . Mean changes from baseline in the SF-36 Mental Component Summary ( MCS ) at week 52 for CZP 200 mg and 400 mg plus MTX , and PBO plus MTX were 6.4 , 6.4 and 2.1 , respectively ( P < 0.001 ) . In addition , mental health and vitality scores in CZP-treated patients approached age- and gender-adjusted US population norms . Improvements in all PROs were sustained . Similar benefits were reported with both CZP doses . Changes in SF-36 MCS scores had the lowest correlation with disease activity scores ( DAS28 ) and American College of Rheumatology 20 % improvement ( ACR20 ) response rates , while improvements in pain showed the highest correlation . Conclusions Treatment with CZP plus MTX result ed in rapid and sustained improvements in all PROs , indicating that the benefits of CZP extend beyond clinical efficacy endpoints into areas that are more relevant and meaningful for patients on a daily basis . Trial Registration Clinical Trials.gov NCT00152386 BACKGROUND Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses . Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis . METHODS In this double-blind , r and omised , placebo-controlled , parallel group phase III study , 623 patients with moderate to severe active rheumatoid arthritis were r and omly assigned with an interactive voice response system , stratified by site with a r and omisation list provided by the study sponsor , to receive tocilizumab 8 mg/kg ( n=205 ) , tocilizumab 4 mg/kg ( 214 ) , or placebo ( 204 ) intravenously every 4 weeks , with methotrexate at stable pre- study doses ( 10 - 25 mg/week ) . Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20 % improvement in both swollen and tender joint counts . The primary endpoint was the proportion of patients with 20 % improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria ( ACR20 response ) at week 24 . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00106548 . FINDINGS The intention-to-treat analysis population consisted of 622 patients : one patient in the 4 mg/kg group did not receive study treatment and was thus excluded . At 24 weeks , ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo ( 120 [ 59 % ] patients in 
    Output:
    