***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: Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-PsA ( NCT01087788 ) , an ongoing Phase 3 trial in patients with psoriatic arthritis ( PsA ) . Methods Patients were r and omised 1:1:1 to placebo  , 200 mg CZP every 2 weeks ( Q2W ) or 400 mg CZP every 4 weeks ( Q4W ) . Patients could have had exposure to one previous tumour necrosis factor ( TNF ) inhibitor therapy . Primary endpoints were American College of Rheumatology 20 % ( ACR20 ) response at week 12 and modified Total Sharp Score change from baseline at week 24 . Secondary endpoints included ; Psoriatic Arthritis Response Criteria ( PsARC ) score , Health Assessment Question naire Disability Index ( HAQ-DI ) , Psoriasis Area and Severity Index , Leeds Enthesitis Index , Leeds Dactylitis Index , and Modified Nail Psoriasis Severity Index . Results Of 409 patients r and omised , 368 completed 24 weeks of treatment .  ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo ( 58.0 % and 51.9 % vs 24.3 % ( p<0.001 ) ) at week 12 , with improvements observed by week 1 . There was a statistically significant improvement in physical function from baseline , measured by HAQ-DI in CZP patients compared with placebo ( −0.50 vs −0.19 , p<0.001 ) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo ( 78.3 % and 77.0 % vs 33.1 % ( p<0.001 ) ) . Sustained improvements were observed in psoriatic skin involvement , enthesitis , dactylitis and nail disease . Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure . No new safety signals were observed . Conclusions Rapid improvements in the signs and symptoms of PsA , including joints , skin , enthesitis , dactylitis and nail disease were observed across both CZP dosing regimens 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 : Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objectives This 52-week , r and omised , double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol ( CZP ) as add-on therapy to non-biologic disease-modifying antirheumatic drugs ( DMARDs ) in rheumatoid arthritis ( RA ) patients with low to moderate disease activity , and stopping therapy in patients in sustained remission . Methods Patients were r and omised 1:1 to CZP ( 400 mg at weeks 0 , 2 and 4 , then 200 mg every 2 weeks )  or placebo ( every 2 weeks  ) plus current non-biologic DMARDs .  At week 24 , patients who achieved the primary endpoint of Clinical Disease Activity Index ( CDAI ) remission at both weeks 20 and 24 stopped study treatment and continued in the study until week 52 . Results Of 194 patients ( CZP=96 ; placebo=98 ) , > 90 % had moderate disease activity at baseline . Significantly more  CZP  patients met the primary endpoint than placebo patients ( week 20 and 24 CDAI remission rates : 18.8 % vs 6.1 % ; p≤0.05 ) . At week 24 , 63.0 % vs 29.7 % of CZP versus placebo patients ( p<0.001 ) achieved LDA . Disease activity score ( ESR ) based on 28-joint count and Simplified Disease Activity Index remission rates were also significantly higher with CZP versus placebo ( 19.8 % vs 3.1 % ; p≤0.01 and 14.6 % vs 4.1 % ; p≤0.05 ) . CZP patients reported improvements in physical function  versus placebo ( mean Health Assessment Question naire-Disability-Index change from baseline : CZP , −0.25 vs placebo , −0.03 ; p≤0.01 ) . During the period following withdrawal of CZP or placebo , only 3/17 prior CZP patients and 2/6 prior placebo patients maintained CDAI remission until week 52 , but CZP reinstitution allowed renewed improvement . Adverse and serious adverse event rates were comparable between CZP and placebo groups . Conclusions Addition of CZP to non-biologic DMARDs is an effective treatment in RA patients with predominantly moderate disease activity , allowing low-disease activity or remission to be reached in a majority of the patients . However , the data suggest that CZP can not be withdrawn in patients achieving remission . Trial registration number NCT00674362 Abstract Objective . This 24-week , placebo-controlled , double-blind , r and omized study ( NCT00791921 ) investigated efficacy and safety of certolizumab pegol ( CZP ) in Japanese rheumatoid arthritis ( RA ) patients in whom methotrexate ( MTX ) can not be administered . Methods . A total of 230 patients were r and omized to subcutaneous CZP 200 mg ( induction dosing : 400 mg at Weeks 0 , 2 and 4 ) or placebo every 2 weeks . Results . ACR20 responses with CZP were rapid and significant versus placebo at Week 1 , sustained to Week 12 ( 67.2 % vs. 14.9 % ) and Week 24 ( 63.8 % vs. 11.4 % ) . Week 24-modified Total Sharp Score ( mTSS ) change from baseline ( CFB ) was 0.48 ( CZP ) versus 2.45 ( placebo ) . CZP treatment was associated with higher Week 12 ACR20 responses versus placebo ( with non-MTX disease modifying antirheumatic drugs [ DMARDs ] , 74.2 % vs. 20.0 % ; without [ monotherapy ] , 59.3 % vs. 8.2 % ) and inhibition of radiographic progression at Week 24 ( mTSS CFB ; with non-MTX DMARDs , 0.24 vs. 1.61 ; monotherapy , 0.68 vs. 3.65 ) . Incidences of serious adverse events were 11.2 % ( CZP ) and 2.6 % ( placebo ) ; one CZP patient died of dissecting aortic aneurysm . Conclusion . CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX can not be administered result ed in rapid , sustained reductions in RA signs and symptoms . Notably , CZP monotherapy showed significant inhibition of radiographic progression Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-axSpA ( NCT01087762 ) , an ongoing Phase 3 trial in patients with axial spondyloarthritis ( axSpA ) , including patients with ankylosing spondylitis ( AS ) and non-radiographic axSpA ( nr-axSpA ) . Methods Patients with active axSpA were r and omised 1:1:1 to placebo , CZP 200 mg every 2 weeks  ( Q2W ) or  CZP 400 mg every 4 weeks ( Q4W ) . In total 325 patients were r and omised . Primary endpoint was ASAS20 ( Assessment of SpondyloArthritis international Society 20 ) response at week 12 . Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , and Bath Ankylosing Spondylitis Metrology Index ( BASMI ) linear . Results Baseline disease activity was similar between AS and nr-axSpA. At week 12 , ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo ( 57.7 and 63.6 vs 38.3 , p≤0.004 ) . At week 24 , combined CZP arms showed significant ( p<0.001 ) differences in change from baseline versus placebo in BASFI ( −2.28 vs −0.40 ) , BASDAI ( −3.05 vs −1.05 ) , and BASMI ( −0.52 vs −0.07 ) . Improvements were observed as early as week 1 . Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA sub population s. Adverse events were reported in 70.4 % vs 62.6 % , and serious adverse events in 4.7 % vs 4.7 % of All CZP versus  placebo groups . No deaths or malignancies were reported . Conclusions CZP rapidly reduced the signs and symptoms of axSpA , with no new safety signals observed compared to the safety profile of CZP in RA . Similar improvements were observed across CZP dosing regim 
    Output:
    
ConclusionS afety data on CZP suggest an overall favorable tolerability profile , with infections being the most common AE .
However ,  CZP-treated  patients had a twofold higher risk of infectious SAEs than control patients .
Large observational studies and data from national registries are needed to detect rare AEs , which might occur after long-term exposures to CZP