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 determine whether patients with rheumatoid arthritis ( RA ) are at increased risk of hospitalized infection and whether the risk varies by RA treatment . METHODS A retrospective cohort study was conducted using data from a medical and pharmacy cl aims managed-care data base from 1999 to 2006 . A total of 24,530 patients were included in the RA cohort ; a r and om sample of non-RA patients served as a comparison cohort ( n = 500,000 ) .  Rates of hospitalized infection were compared between the cohorts . A nested case-control analysis was performed within the RA cohort to assess the effect of current RA medication use on hospitalized infection risk . RESULTS A total of 1,993 patients with RA and 11,977 non-RA patients experienced a hospitalized infection . The rate of first hospitalized infection was higher in the RA cohort [ adjusted hazard ratio = 2.03 ; 95 % confidence interval ( CI ) 1.93 - 2.13 ] . In the case-control analysis , the current use of biological disease modifying antirheumatic drugs ( DMARD ) was associated with slightly increased risk of hospitalized infection [ rate ratio ( RR ) = 1.21 ; 95 % CI 1.02 - 1.43 ] . Methotrexate and hydroxychloroquine were associated with decreased risk .  Oral corticosteroid use increased risk ( RR = 1.92 ; 95 % CI 1.67 - 2.21 ) , and there was a dose-related effect [ < or = 5 mg/day : RR = 1.32 ( 95 % CI 1.06 - 1.63 ) , 6 - 10 mg/day : RR = 1.94 ( 95 % CI 1.53 - 2.46 ) , > 10 mg/day : RR = 2.98 ( 95 % CI 2.41 - 3.69 ) ] . CONCLUSION These data confirm that individuals with RA are at increased risk of hospitalized infection compared to those without RA . Oral corticosteroid use was associated with a dose-related increase . Biological DMARD use was associated with slightly elevated risk ; however , this may reflect confounding and channeling bias OBJECTIVE To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis ( RA ) . METHODS MTX-naive patients with RA ( n = 637 ) were r and omized to receive placebo plus MTX ( group 1 ) , golimumab 100 mg plus placebo ( group 2 ) , golimumab 50 mg plus MTX ( group 3 ) , or golimumab 100 mg plus MTX ( group 4 ) . Subcutaneous injections of golimumab or placebo were administered every 4 weeks . The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week . The primary end point , the proportion of patients meeting the American College of Rheumatology 50 % improvement criteria ( achieving an ACR50 response ) at week 24 , required significant differences between groups 3 and 4 combined ( combined group ) versus group 1 and significant differences in a pairwise comparison ( group 3 or group 4 versus group 1 ) . RESULTS An intent-to-treat ( ITT ) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 ( 38.4 % and 29.4 % , respectively ; P=0.053 ) , while a post hoc modified ITT analysis ( excluding 3 untreated patients ) of the ACR50 response showed statistically significant differences between the combined group and group 1 ( 38.5 % versus 29.4 % ; P=0.049 ) and between group 3 ( 40.5 % ; P=0.038 ) but not group 4 ( 36.5 % ; P=0.177 ) and group 1 . Group 2 was noninferior to group 1 for the ACR50 response at week 24 ( 33.1 % ; 95 % confidence interval lower bound -5.2 % ; predefined delta value for noninferiority -10 % ) . The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters , including response/remission according to the Disease Activity Score in 28 joints . Serious adverse events occurred in 7 % , 3 % , 6 % , and 6 % of patients in groups 1 , 2 , 3 , and 4 , respectively . CONCLUSION Although the primary end point was not met , the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than , and the efficacy of golimumab alone is similar to , the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients , with no unexpected safety concerns OBJECTIVE To evaluate the safety of anakinra ( a recombinant human interleukin-1 receptor antagonist ) in a large population of patients with rheumatoid arthritis ( RA ) , typical of those seen in clinical practice . METHODS A total of 1,414 patients were r and omly assigned to treatment with 100 mg of anakinra or placebo , administered daily by subcutaneous injection . Background medications included disease-modifying antirheumatic drugs , corticosteroids , and nonsteroidal antiinflammatory drugs , alone or in combination . The primary end point was safety , which was evaluated by adverse events ( including infections ) , discontinuation from study due to adverse events , and death . RESULTS Safety was evaluated in 1,399 patients ( 1,116 in the anakinra group and 283 in the placebo group ; 15 patients were r and omized but did not receive any study drug ) during the initial 6-month , double-blind , placebo-controlled phase of this long-term safety study . Baseline demographics , disease characteristics , and concomitant medications were similar between the 2 groups . The study group included patients with numerous comorbid conditions and a wide range of RA disease activity .  Serious adverse events occurred at a similar rate in the anakinra group and the placebo group ( 7.7 % and 7.8 % , respectively ) . Serious infectious episodes were observed more frequently in the anakinra group ( 2.1 % versus 0.4 % in the placebo group ) . The rate of withdrawal due to adverse events was 13.4 % in the anakinra group and 9.2 % in the placebo group . CONCLUSION Results from this large , placebo-controlled safety study demonstrate that anakinra is safe and well tolerated in a diverse population of patients with RA , including those with comorbid conditions and those using multiple combinations of concomitant therapies . Although the frequency of serious infection was slightly higher in the anakinra group , no infection was attributed to opportunistic microorganisms or result ed in death 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 : OBJECTIVES To compare budesonide , a locally acting glucocorticoid with minimal systemic exposure , with conventional glucocorticoid treatment and placebo in rheumatoid arthritis . METHODS A double blind , r and omised , controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis , comparing budesonide 3 mg daily , budesonide 9 mg daily , prednisolone 7.5 mg daily , and placebo . Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment . RESULTS There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo ( 28 % for tender and 34 % for swollen joint counts , p<0.05 ) . Prednisolone 7.5 mg gave similar results , while budesonide 3 mg was less effective . ACR20 response criteria were met by 25 % of patients on placebo , 22 % on budesonide 3 mg , 42 % on budesonide 9 mg , and 56 % on prednisolone 7.5 mg . A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks . There was no evidence that budesonide provided a different pattern of symptom control from prednisolone , or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment . Adverse effects attributable to glucocorticoids were equally common in all groups . CONCLUSIONS The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment , are maintained for three months , and are not associated with any rebound in symptoms after stopping treatment 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 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 interleuk 
    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: OBJECTIVE To determine whether patients with rheumatoid arthritis ( RA ) are at increased risk of hospitalized infection and whether the risk varies by RA treatment . METHODS A retrospective cohort study was conducted using data from a medical and pharmacy cl aims managed-care data base from 1999 to 2006 . A total of 24,530 patients were included in the RA cohort ; a r and om sample of non-RA patients served as a comparison cohort ( n = 500,000 ) .  Rates of hospitalized infection were compared between the cohorts . A nested case-control analysis was performed within the RA cohort to assess the effect of current RA medication use on hospitalized infection risk . RESULTS A total of 1,993 patients with RA and 11,977 non-RA patients experienced a hospitalized infection . The rate of first hospitalized infection was higher in the RA cohort [ adjusted hazard ratio = 2.03 ; 95 % confidence interval ( CI ) 1.93 - 2.13 ] . In the case-control analysis , the current use of biological disease modifying antirheumatic drugs ( DMARD ) was associated with slightly increased risk of hospitalized infection [ rate ratio ( RR ) = 1.21 ; 95 % CI 1.02 - 1.43 ] . Methotrexate and hydroxychloroquine were associated with decreased risk .  Oral corticosteroid use increased risk ( RR = 1.92 ; 95 % CI 1.67 - 2.21 ) , and there was a dose-related effect [ < or = 5 mg/day : RR = 1.32 ( 95 % CI 1.06 - 1.63 ) , 6 - 10 mg/day : RR = 1.94 ( 95 % CI 1.53 - 2.46 ) , > 10 mg/day : RR = 2.98 ( 95 % CI 2.41 - 3.69 ) ] . CONCLUSION These data confirm that individuals with RA are at increased risk of hospitalized infection compared to those without RA . Oral corticosteroid use was associated with a dose-related increase . Biological DMARD use was associated with slightly elevated risk ; however , this may reflect confounding and channeling bias OBJECTIVE To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis ( RA ) . METHODS MTX-naive patients with RA ( n = 637 ) were r and omized to receive placebo plus MTX ( group 1 ) , golimumab 100 mg plus placebo ( group 2 ) , golimumab 50 mg plus MTX ( group 3 ) , or golimumab 100 mg plus MTX ( group 4 ) . Subcutaneous injections of golimumab or placebo were administered every 4 weeks . The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week . The primary end point , the proportion of patients meeting the American College of Rheumatology 50 % improvement criteria ( achieving an ACR50 response ) at week 24 , required significant differences between groups 3 and 4 combined ( combined group ) versus group 1 and significant differences in a pairwise comparison ( group 3 or group 4 versus group 1 ) . RESULTS An intent-to-treat ( ITT ) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 ( 38.4 % and 29.4 % , respectively ; P=0.053 ) , while a post hoc modified ITT analysis ( excluding 3 untreated patients ) of the ACR50 response showed statistically significant differences between the combined group and group 1 ( 38.5 % versus 29.4 % ; P=0.049 ) and between group 3 ( 40.5 % ; P=0.038 ) but not group 4 ( 36.5 % ; P=0.177 ) and group 1 . Group 2 was noninferior to group 1 for the ACR50 response at week 24 ( 33.1 % ; 95 % confidence interval lower bound -5.2 % ; predefined delta value for noninferiority -10 % ) . The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters , including response/remission according to the Disease Activity Score in 28 joints . Serious adverse events occurred in 7 % , 3 % , 6 % , and 6 % of patients in groups 1 , 2 , 3 , and 4 , respectively . CONCLUSION Although the primary end point was not met , the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than , and the efficacy of golimumab alone is similar to , the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients , with no unexpected safety concerns OBJECTIVE To evaluate the safety of anakinra ( a recombinant human interleukin-1 receptor antagonist ) in a large population of patients with rheumatoid arthritis ( RA ) , typical of those seen in clinical practice . METHODS A total of 1,414 patients were r and omly assigned to treatment with 100 mg of anakinra or placebo , administered daily by subcutaneous injection . Background medications included disease-modifying antirheumatic drugs , corticosteroids , and nonsteroidal antiinflammatory drugs , alone or in combination . The primary end point was safety , which was evaluated by adverse events ( including infections ) , discontinuation from study due to adverse events , and death . RESULTS Safety was evaluated in 1,399 patients ( 1,116 in the anakinra group and 283 in the placebo group ; 15 patients were r and omized but did not receive any study drug ) during the initial 6-month , double-blind , placebo-controlled phase of this long-term safety study . Baseline demographics , disease characteristics , and concomitant medications were similar between the 2 groups . The study group included patients with numerous comorbid conditions and a wide range of RA disease activity .  Serious adverse events occurred at a similar rate in the anakinra group and the placebo group ( 7.7 % and 7.8 % , respectively ) . Serious infectious episodes were observed more frequently in the anakinra group ( 2.1 % versus 0.4 % in the placebo group ) . The rate of withdrawal due to adverse events was 13.4 % in the anakinra group and 9.2 % in the placebo group . CONCLUSION Results from this large , placebo-controlled safety study demonstrate that anakinra is safe and well tolerated in a diverse population of patients with RA , including those with comorbid conditions and those using multiple combinations of concomitant therapies . Although the frequency of serious infection was slightly higher in the anakinra group , no infection was attributed to opportunistic microorganisms or result ed in death 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 : OBJECTIVES To compare budesonide , a locally acting glucocorticoid with minimal systemic exposure , with conventional glucocorticoid treatment and placebo in rheumatoid arthritis . METHODS A double blind , r and omised , controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis , comparing budesonide 3 mg daily , budesonide 9 mg daily , prednisolone 7.5 mg daily , and placebo . Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment . RESULTS There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo ( 28 % for tender and 34 % for swollen joint counts , p<0.05 ) . Prednisolone 7.5 mg gave similar results , while budesonide 3 mg was less effective . ACR20 response criteria were met by 25 % of patients on placebo , 22 % on budesonide 3 mg , 42 % on budesonide 9 mg , and 56 % on prednisolone 7.5 mg . A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks . There was no evidence that budesonide provided a different pattern of symptom control from prednisolone , or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment . Adverse effects attributable to glucocorticoids were equally common in all groups . CONCLUSIONS The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment , are maintained for three months , and are not associated with any rebound in symptoms after stopping treatment 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 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 interleuk 
    Output:
    