***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 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 : Introduction The efficacy and safety of tocilizumab in patients with rheumatoid arthritis have been evaluated in a comprehensive phase 3 program . Patients from these r and omized trials could receive tocilizumab treatment in open-label extension trials . Here , the long-term safety profile of tocilizumab , using pooled data from all of these trials , is reported . Methods Cumulative safety data ( as of February 6 , 2009 ) from five core phase 3 trials , two ongoing extension trials , and one clinical pharmacology study were analyzed . Two patient population s were evaluated : an all-control population ( n = 4,199 ) , which included all patients r and omly assigned in the placebo-controlled portions of the five core studies , and an all-exposed population ( n = 4,009 ) , which included patients from any of the eight studies who received at least one dose of tocilizumab .  Results Total exposure to tocilizumab was 8,580 patient years ( PY ) , and total duration of observation was 9,414 PY . Overall adverse event ( AE ) and serious AE ( SAE ) rates were 278.2/100 PY and 14.4/100 PY , respectively . These events included serious infections ( 4.7/100 PY ) , opportunistic infections ( 0.23/100 PY ) , gastrointestinal perforations ( 0.28/100 PY ) , malignancy ( 1.1/100 PY ) , myocardial infa rct ion ( 0.25/100 PY ) , and stroke ( 0.19/100 PY ) . The rates of SAEs and serious infections were stable over time ; no increase with prolonged exposure was noted . Conclusions The longer-term safety profile of tocilizumab ( mean treatment duration , 2.4 years ) is consistent with that observed in the phase 3 studies ( duration up to 1 year ) Objective : To evaluate the safety and effectiveness of adalimumab alone or in combination with st and ard disease-modifying antirheumatic drugs ( DMARDs ) for the treatment of rheumatoid arthritis ( RA ) . Methods : Patients with active RA despite treatment with DMARDs or prior treatment with a tumour necrosis factor antagonist participated in a multicentre , open-label clinical study of adalimumab 40 mg every other week for 12 weeks with an optional extension phase . Patients were allowed to continue with pre-existing traditional DMARDs .  Long-term safety results are reported for all patients ( 4210 patient-years ( PYs ) of adalimumab  exposure ) . The observed effectiveness results at week 12 are reported using American College of Rheumatology ( ACR ) and European League Against Rheumatism ( EULAR ) response criteria . Results : Among the 6610 treated patients , adalimumab was generally well tolerated . Serious infections occurred in 3.1 % of patients ( 5.5/100 PYs , including active tuberculosis , 0.5/100 PYs ) . Demyelinating disease ( 0.06 % ) and systemic lupus erythematosus ( 0.03 % ) were rare serious adverse events . The st and ardised incidence ratio of malignancy was 0.71 ( 95 % CI 0.49 to 1.01 ) . The st and ardised mortality ratio was 1.07 ( 95 % CI 0.75 to 1.49 ) . At week 12 , 69 % of patients achieved an ACR20 response , 83 % a moderate , and 33 % a good EULAR response .  Adalimumab was effective in combination with a variety of DMARDs . The addition of adalimumab to antimalarials was comparably effective to the combination of adalimumab and methotrexate . Conclusions : Considering the limitations of an open-label study , adalimumab alone or in combination with st and ard DMARDs appeared to be well tolerated and effective in 6610 difficult-to-treat patients with active RA treated in clinical practice Objectives : To evaluate the safety and efficacy of 5-year , long-term tocilizumab monotherapy for patients with rheumatoid arthritis . Methods : In an open-label , long-term extension trial following an initial 3-month r and omised phase II trial , 143 of the 163 patients who participated in the initial blinded study received tocilizumab monotherapy ( 8 mg/kg ) every 4 weeks . Concomitant therapy with non-steroidal anti-inflammatory drugs and /or oral prednisolone ( 10 mg daily maximum ) was permitted . All patients were evaluated with American College of Rheumatology ( ACR ) improvement criteria , disease activity score ( DAS ) in 28 joints , and the European League Against Rheumatism response , as well as for safety issues . Results : 143 patients were enrolled in the open-label , long-term extension trial and 94 ( 66 % ) patients had completed 5 years as of March 2007 . 32 patients ( 22 % ) withdrew from the study due to adverse events and one patient ( 0.7 % ) due to unsatisfactory response . 14 patients withdrew because of the patient ’s request or other reasons . The serious adverse event rate was 27.5 events per 100 patient-years , with 5.7 serious infections per 100 patient-years , based on a total tocilizumab exposure of 612 patient-years . Of the 88 patients receiving corticosteroids at baseline , 78 ( 88.6 % ) were able to decrease their corticosteroid dose and 28 ( 31.8 % ) discontinued corticosteroids . At 5 years , 79/94 ( 84.0 % ) , 65/94 ( 69.1 % ) and 41/94 ( 43.6 % ) of the patients achieved ACR20 , ACR50 , and ACR70 improvement criteria , respectively . Remission defined as DAS28 less than 2.6 was achieved in 52/94 ( 55.3 % ) of the patients . Conclusion : In this 5-year extension study , tocilizumab demonstrated sustained long-term efficacy and a generally good safety profile 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 rheumato 
    Output:
    
The data on serious infection may be used to evaluate the public health risk and benefit of biologic treatment .