***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: Introduction The objective of this study was to directly compare the safety of tocilizumab ( TCZ ) and TNF inhibitors ( TNFIs ) in rheumatoid arthritis ( RA ) patients in clinical practice . Methods This prospect i ve cohort study included RA patients starting TCZ [ TCZ group , n = 302 , 224.68 patient-years ( PY ) ] or TNFIs [ TNFI group , n = 304 , 231.01 PY ] from 2008 to 2011 in the registry of Japanese RA patients on biologics for long-term safety registry . We assessed types and incidence rates ( IRs ) of serious adverse events ( SAEs ) and serious infections ( SIs ) during the first year of treatment . Risks of the biologics for SAEs or SIs were calculated using the Cox regression hazard analysis . Results Patients in the TCZ group had longer disease duration ( P < 0.001 ) , higher disease activity ( P = 0.019 ) and more frequently used concomitant corticosteroids ( P < 0.001 ) than those in the TNFI group . The crude IR ( /100 PY ) of SIs  [ TCZ 10.68 vs. TNFI 3.03 ; IR ratio ( 95 % confidence interval [ CI ] ) , 3.53 ( 1.52 to 8.18 ) ] , but not SAEs [ 21.36 vs. 14.72 ; 1.45 ( 0.94 to 2.25 ) ] , was significantly higher in the TCZ group compared with the TNFI group . However , after adjusting for covariates using the Cox regression hazard analysis , treatment with TCZ was not associated with higher risk for SAEs [ hazard ratio ( HR ) 1.28 , 95 % CI 0.75 to 2.19 ] or SIs ( HR 2.23 , 95 % CI 0.93 to 5.37 ) . Conclusions The adjusted risks for SAEs and SIs were not significantly different between TCZ and TNFIs , indicating an influence of clinical characteristics of the patients on the safety profile of the biologics in clinical practice CONTEXT High levels of lipoprotein(a ) are associated with increased risk of myocardial infa rct ion ( MI ) . OBJECTIVE To assess whether genetic data are consistent with this association being causal . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a prospect i ve general population study with 16 years of follow-up ( 1991 - 2007 , n = 8637 , 599 MI events ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( 2003 - 2006 , n = 29 388 , 994 MI events ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( 1991 - 2004 , n = 2461 , 1231 MI events ) . MAIN OUTCOME MEASURES Plasma lipoprotein(a ) levels , lipoprotein(a ) kringle IV type 2 ( KIV-2 ) size polymorphism genotype , and MIs recorded from 1976 through July 2007 for all participants . RESULTS In the CCHS , multivariable-adjusted hazard ratios ( HRs ) for MI for elevated lipoprotein(a ) levels were 1.2 ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; events/10,000 person-years , 59 ) for levels between the 22nd and 66th percentile , 1.6 ( 95 % CI , 1.1 - 2.2 ; events/10,000 person-years , 75 ) for the 67th to 89th percentile , 1.9 ( 95 % CI , 1.2 - 3.0 ; events/10,000 person-years , 84 ) for the 90th to 95th percentile , and 2.6 ( 95 % CI , 1.6 - 4.1 ; events/10,000 person-years , 108 ) for levels greater than the 95th percentile , respectively , vs levels less than the 22nd percentile ( events/10,000 person-years , 55 ) ( trend P < .001 ) . Numbers of KIV-2 repeats ( sum of repeats on both alleles ) ranged from 6 to 99 and on analysis of variance explained 21 % and 27 % of all variation in plasma lipoprotein(a ) levels in the CCHS and CGPS , respectively . Mean lipoprotein(a ) levels were 56 , 31 , 20 , and 15 mg/dL for the first , second , third , and fourth quartiles of KIV-2 repeats in the CCHS , respectively ( trend P < .001 ) ; corresponding values in the CGPS were 60 , 34 , 22 , and 19 mg/dL ( trend P < .001 ) . In the CCHS , multivariable-adjusted HRs for MI were 1.5 ( 95 % CI , 1.2 - 1.9 ; events/10,000 person-years , 75 ) , 1.3 ( 95 % CI , 1.0 - 1.6 ; events/10,000 person-years , 66 ) , and 1.1 ( 95 % CI , 0.9 - 1.4 ; events/10,000 person-years , 57 ) for individuals in the first , second , and third quartiles , respectively , as compared with individuals in the fourth quartile of KIV-2 repeats ( events/10,000 person-years , 51 ) ( trend P < .001 ) . Corresponding odds ratios were 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.1 ( 95 % CI , 0.9 - 1.3 ) , and 0.9 ( 95 % CI , 0.8 - 1.1 ) in the CGPS ( trend P = .005 ) , and 1.4 ( 95 % CI , 1.1 - 1.7 ) , 1.2 ( 95 % CI , 1.0 - 1.6 ) , and 1.3 ( 95 % CI , 1.0 - 1.6 ) in the CIHDS ( trend P = .01 ) . Genetically elevated lipoprotein(a ) was associated with an HR of 1.22 ( 95 % CI , 1.09 - 1.37 ) per doubling of lipoprotein(a ) level on instrumental variable analysis , while the corresponding value for plasma lipoprotein(a ) levels on Cox regression was 1.08 ( 95 % CI , 1.03 - 1.12 ) . CONCLUSION These data are consistent with a causal association between elevated lipoprotein(a ) levels and increased risk of MI BACKGROUND To date , head-to-head trials comparing the efficacy and safety of biological disease-modifying antirheumatic drugs within the same class , including TNF inhibitors , in patients with active rheumatoid arthritis despite methotrexate therapy are lacking . We aim ed to compare the efficacy and safety of two different TNF inhibitors and to assess the efficacy and safety of switching to the other TNF inhibitor without a washout period after insufficient primary response to the first TNF inhibitor at week 12 . METHODS In this 104-week , r and omised , single-blind ( double-blind until week 12 and investigator blind thereafter ) , parallel-group , head-to-head superiority study ( EXXELERATE ) , eligible patients from 151 centres worldwide were aged 18 years or older with a diagnosis of rheumatoid arthritis at screening , as defined by the 2010 ACR/EULAR criteria , and had prognostic factors for severe disease progression , including a positive rheumatoid factor , or anti-cyclic citrullinated peptide antibody result , or both . Participants were r and omly assigned ( 1:1 ) via an interactive voice and web response system with no stratification to receive certolizumab pegol plus methotrexate or adalimumab plus methotrexate . All study staff were kept masked throughout the study and participants were masked until week 12 . At week 12 , patients were classified as responders ( by either achieving low disease activity [ LDA ] according to Disease Activity Score 28-erythrocyte sedimentation rate [ DAS28-ESR ] ≤3·2 or DAS28-ESR reduction ≥1·2 from baseline ) or as non-responders . Non-responders to the first TNF inhibitor to which they were r and omised were switched to the other TNF inhibitor with no washout period . Primary endpoints were the percentage of patients achieving a 20 % improvement according to the American College of Rheumatology criteria ( ACR20 ) at week 12 and LDA at week 104 ( week 12 non-responders were considered LDA non-responders ) . This study is registered with Clinical Trials.gov , number NCT01500278 . FINDINGS Between Dec 14 , 2011 , and Nov 11 , 2013 , 1488 patients were screened of whom 915 were r and omly assigned ; 457 to certolizumab pegol plus methotrexate and 458 to adalimumab plus methotrexate . No statistically significant difference was observed in ACR20 response at week 12 ( 314 [ 69 % ] of 454 patients and 324 [ 71 % ] of 454 patients ; odds ratio [ OR ] 0·90 [ 95 % CI 0·67 - 1·20 ] ; p=0·467 ) or DAS28-ESR LDA at week 104 ( 161 [ 35 % ] of 454 patients and 152 [ 33 % ] of 454 patients ; OR 1·09 [ 0·82 - 1·45 ] ; p=0·532 ) between certolizumab pegol plus methotrexate and adalimumab plus methotrexate , respectively . At week 12 , 65 non-responders to certolizumab pegol were switched to adalimumab and 57 non-responders to adalimumab were switched to certolizumab pegol ; 33 ( 58 % ) of 57 patients switching to certolizumab pegol and 40 ( 62 % ) of 65 patients switching to adalimumab responded 12 weeks later by achieving LDA or a DAS28-ESR reduction 1·2 or greater . 389 [ 75 % ] of 516 patients who received certolizumab pegol plus methotrexate and 386 [ 74 % ] of 523 patients who received adalimumab plus methotrexate reported treatment-emergent adverse events . Three deaths ( 1 % ) occurred in each group . No serious infection events were reported in the 70-day period after treatment switch . INTERPRETATION These results show that certolizumab pegol plus methotrexate is not superior to adalimumab plus methotrexate . The data also show the clinical benefit and safety of switching to a second TNF inhibitor without a washout period after primary failure to a first TNF inhibitor . FUNDING UCB Pharma Objectives The interleukin-6 receptor ( IL-6R ) blocker tocilizumab ( TCZ ) reduces inflammatory disease activity in rheumatoid arthritis ( RA ) but elevates lipid concentrations in some patients . We aim ed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA . Methods R and omised , multicentre , two-part , phase III trial ( 24-week double-blind , 80-week open-label ) , MEASURE , evaluated lipid and lipoprotein levels , high-density lipoprotein ( HDL ) particle composition , markers of coagulation , thrombosis and vascular function by pulse wave velocity ( PWV ) in 132 patients with RA who received TCZ or placebo .  Results Median total-cholesterol , low-density lipoprotein-cholesterol ( LDL-C ) and triglyceride levels increased in TCZ versus placebo recipients by week 12 ( 12.6 % vs 1.7 % , 28.1 % vs 2.2 % , 10.6 % vs −1.9 % , respectively ; all p<0.01 ) . There were no significant differences in mean small LDL , mean oxidised LDL or total HDL-C concentrations . However , HDL-associated serum amyloid A content decreased in TCZ recipients . TCZ also induced reductions ( > 30 % ) in secretory phospholipase A2-IIA , lipoprotein(a ) , fibrinogen and D-dimers and elevation of paraoxonase ( all p<0.0001 vs placebo ) . The ApoB/ApoA1 ratio remained stable over time in both groups . PWV decreases were greater with placebo than TCZ at 12 
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Conclusions Despite an increase in cholesterol levels , TCZ has safe cardiovascular outcomes compared to other bDMARD