***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 assess the impact of certolizumab pegol ( CZP ) , a novel PEGylated anti-tumor necrosis factor , in combination with methotrexate ( MTX ) on productivity outside and within the home , and on participation in family , social , and leisure activities in adult patients with rheumatoid arthritis ( RA ) . METHODS The efficacy and safety of CZP ( 200 mg and 400 mg ) plus MTX were assessed in 2 phase III , multicenter , double-blind , placebo-controlled trials ( Rheumatoid Arthritis Prevention of Structural Damage [ RAPID ] 1 and RAPID 2 ) . The novel , vali date d , RA-specific Work Productivity Survey ( WPS-RA ) was used to assess work place and home productivity . WPS-RA responses were collected at baseline and every 4 weeks until withdrawal/ study completion . RESULTS At baseline , 41.6 % and 39.8 % of subjects were employed outside the home in RAPID 1 and RAPID 2 , respectively . Compared with placebo plus MTX , CZP plus MTX significantly reduced work absenteeism and presenteeism among patients working outside the home . Significant reductions in number of household days lost , household days with productivity reduced by > /=50 % , and days lost due to RA for participation in family , social , and leisure activities were reported by patients in active treatment relative to placebo plus MTX . Improvements in all measures were observed with CZP plus MTX as early as week 4 , and maintained until the study end ( 12 months in RAPID 1 , 6 months in RAPID 2 ) . Findings were consistent with clinical improvements with CZP plus MTX in both trials . CONCLUSION CZP plus MTX improved productivity outside and within the home and result ed in more participation in social activities compared with placebo plus MTX . These observations suggest that considerable indirect cost gains might be achieved with this therapeutic agent in RA Objective : The objective of this exploratory study was to evaluate the effects and costs of a 6‐month course of tumour necrosis factor ( TNF ) inhibitors on work ability , quality of life , and fatigue in patients with rheumatoid arthritis ( RA ) . Methods : In this prospect i ve single‐arm intervention study 59 consecutive patients of working age with established RA were recruited from an outpatient clinic in Amsterdam , the Netherl and s. All patients received fortnightly subcutaneous injections of 40 mg adalimumab . The three outcomes at baseline and 6 months were : perceived work ability [ Work Ability Index ( WAI ) ] , quality of life [ Rheumatoid Arthritis Quality of Life instrument ( RAQoL ) ] , and fatigue [ Checklist Individual Strength ( CIS ) , Need for Recovery ( NFR ) scale ] . Cost data of the preceding 6 months were collected using a self‐administered patient question naire at baseline and follow‐up . Results : At 6 months , all outcomes showed a statistically significant improvement in mean scores from baseline , ranging from 10.0 % ( WAI ) , to 11.7 % ( RAQoL ) , to 15 % ( NFR ) ( subgroup paid work , n = 26 ) . The total mean costs showed a twofold increase in mean costs per week per patient [ difference EUR 169 , 95 % confidence interval ( CI ) EUR 113–226 ] . Conclusions : In this short‐term exploratory evaluation , a 6‐month course of TNF inhibitors  improved work ability and quality of life , and reduced fatigue in patients with established RA . These effects are associated with an increase in total healthcare costs , attributable to the costs of TNF inhibitors . R and omized controlled trials with a longer follow‐up are needed to show a long‐term effect on work disability and the potential cost‐effectiveness of TNF inhibitors OBJECTIVES To compare the impact of the combination of etanercept ( ETN ) and MTX with MTX alone on work productivity among  MTX-naïve patients with active early RA over a 12-month period . METHODS The COMET ( COmbination of Methotrexate and ETanercept ) trial was a 2-year double-blind r and omized clinical trial . Absenteeism during the first year was measured and it included : ( i ) number of missed workdays ; ( ii ) reduced working time ; and ( iii ) number of stopped workdays . Each absenteeism measure was estimated using a mixed model , and their variations were estimated by bootstrapping . As a sensitivity analysis , the lost workdays due to presenteeism ( reduced performance at work ) was also estimated . RESULTS Two hundred and five patients [ MTX ( n = 100 ) vs ETN + MTX ( n = 105 ) ] , who were working full time or part time at baseline and had at least one follow-up observation , were included in the analysis . Compared with the MTX group , the ETN + MTX group had a maximum of 37 fewer missed workdays or at minimum 22 fewer missed workdays . The associated productivity gain equalled 2586 pounds and 1555 pounds , respectively . When additionally accounting for presenteeism , the total improvement could be as high as 42 ( 95 % CI 16 , 69 ) fewer lost workdays representing a productivity gain of 2968 pounds . CONCLUSIONS Our results demonstrated that early treatment with ETN + MTX led to a significant attenuation of absenteeism among patients with early active RA . These productivity gains represent benefit beyond the traditional measures of clinical and radiographic improvements . Further research to simultaneously measure both absenteeism and presenteeism is warranted OBJECTIVE To evaluate the shortterm effect of adalimumab on work productivity in patients with moderate to severe active rheumatoid arthritis ( RA ) . METHODS In a sub study of the Canadian Adalimumab Clinical Trial ( CanAct ) , clinical , health status , and productivity outcomes were measured at baseline and 12 weeks . Patients were classified as responders and nonresponders by the 20 % American College of Rheumatology ( ACR20 ) improvement criterion and the minimum clinical ly important difference ( MCID ) of the Health Assessment Question naire ( HAQ ) score ( 0.22 ) , respectively . The Health and Labour Question naire  ( HLQ ) was used to measure productivity outcomes and costs . RESULTS Included in the analysis were 389 patients completing both baseline and 12-week HLQ question naire . Absenteeism ( a decrease of 0.5 workdays per 2 weeks ) and unpaid work productivity ( 3.5 fewer hours unpaid help per 2 weeks ) were improved significantly after 12 weeks . Improvements in productivity outcomes were associated with clinical response . Bootstrapping results suggest that responders achieved statistically significant improvement in presenteeism ( ACR20 ) and unpaid work productivity ( ACR20 and HAQ ) versus nonresponders . The costs saved by responders were up to $ 155.04 per 2 weeks more than those by nonresponders . CONCLUSION The costs of adalimumab were partially offset , even in the short term , by cost savings induced by clinical response among Canadian patients with moderate to severe RA . These findings complement results of other study analyses that demonstrate early and sustained benefits of adalimumab OBJECTIVE To compare work disability and job loss in early rheumatoid arthritis ( RA ) patients receiving adalimumab plus methotrexate ( adalimumab + MTX ) versus MTX alone .  METHODS In this multicenter , r and omized , controlled trial , patients with RA for < 2 years who had never taken MTX and who self-reported work impairment were r and omized to  adalimumab + MTX or placebo + MTX for 56 weeks . Primary outcome was job loss of any cause and /or imminent job loss at or after week 16 . Secondary outcomes included disease activity , function ( Health Assessment Question naire [ HAQ ] score ) , and RA quality of life ( RAQoL ) question naire score . Work was evaluated with work diaries and the RA Work Instability Scale . RESULTS Although job loss during the 56-week study was significantly lower with adalimumab + MTX ( 14 of 75 patients ) compared with MTX alone ( 29 of 73 patients ; P=0.005 ) , the primary end point was not met ( 12 of 75 versus 20 of 73 patients ; P=0.092 ) , likely owing to early drop out in the MTX group . There were significant improvements in American College of Rheumatology 20 % response criteria , 28-joint Disease Activity Score , DeltaHAQ , DeltaRAQoL , and working time lost in the adalimumab + MTX group . Twenty-four serious adverse events were reported in 17 participants , with no differences between groups . CONCLUSION Adalimumab + MTX reduced job loss and improved productivity in early RA when compared with MTX alone , which supports the early use of anti-tumor necrosis factor therapy and suggests its cost efficacy OBJECTIVE To evaluate the efficacy and safety of 2 dosage regimens of lyophilized certolizumab pegol ( a novel PEGylated anti-tumor necrosis factor agent ) as adjunctive therapy to methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) with an inadequate response to MTX therapy alone . METHODS In this 52-week , phase III , multicenter , r and omized , double-blind , placebo-controlled , parallel-group trial , 982 patients were r and omized 2:2:1 to receive treatment with subcutaneous certolizumab pegol at an initial dosage of 400 mg given at weeks 0 , 2 , and 4 , with a subsequent dosage of 200 mg or 400 mg given every 2 weeks , plus MTX , or placebo plus MTX . Co- primary end points were the response rate at week 24 according to the American College of Rheumatology 20 % criteria for improvement ( ACR20 ) and the mean change from baseline in the modified total Sharp score at week 52 . RESULTS At week 24 , ACR20 response rates using nonresponder imputation for the certolizumab pegol 200-mg and 400-mg groups were 58.8 % and 60.8 % , respectively , as compared with 13.6 % for the placebo group . Differences in ACR20 response rates versus placebo were significant at week 1 and were sustained to week 52 ( P < 0.001 ) . At week 52 , mean radiographic progression from baseline was reduced in patients treated with certolizumab pegol 200 mg ( 0.4 Sharp units ) or 400 mg ( 0.2 Sharp units ) as compared with that in placebo-treated patients ( 2.8 Sharp units ) ( P < 0.001 by rank analysis ) . Improvements in all ACR core set of disease activity measures , including physical function , were observed by week 1 with both certolizumab pegol dosage regimens . Most adverse events were mild or moderate . CONCLUSION Treatment with certolizumab pegol 200 or 400 mg plus MTX result ed in a rapid and sustained reduction in RA signs and symptoms , inhibited the progression of structural joint damage , and improved physical function as compared with placebo plus MTX treatment in RA patients with an incomplete response to MTX Objective To investigate the effect of tumour necrosis factor ( TNF ) 
    Output:
    
RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying  antirheumatic drugs ( DMARD ) , continuing the failing DMARD , the general population or the situation before the start of biological agents .
The effect on employment status was more conflicting , but 50 % of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status