Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study.

To investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept. Using claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection. To control for >70 confounders, TCZ initiators were propensity score (PS)-matched to TNFi or abatacept initiators. Database-specific HRs were combined by a meta-analysis. The primary cohort included 16 074 TCZ PS-matched to 33 109 TNFi initiators. The risk of composite SI was not different between TCZ and TNFi initiators (combined HR 1.05, 95% CI 0.95 to 1.16). However, TCZ was associated with an increased risk of serious bacterial infection (HR 1.19, 95% CI 1.07 to 1.33), skin and soft tissue infections (HR 2.38, 95% CI 1.47 to 3.86), and diverticulitis (HR 2.34, 95% CI 1.64 to 3.34) versus TNFi. An increased risk of composite SI, serious bacterial infection, diverticulitis, pneumonia/upper respiratory tract infection and septicaemia/bacteraemia was observed in TCZ versus abatacept users. This large multidatabase cohort study found no difference in composite SI risk in patients with RA initiating TCZ versus TNFi after failing ≥1 biologic drug or tofacitinib. However, the risk of serious bacterial infection, skin and soft tissue infections, and diverticulitis was higher in TCZ versus TNFi initiators. The risk of composite SI was higher in TCZ initiators versus abatacept.

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Competing interests: SCK has received research grants to the Brigham and Women’s Hospital from Roche, Pfizer and Bristol-Myers Squibb. DHS has received research grants to the Brigham and Women’s Hospital from Pfizer, Genentech, Amgen, AbbVie, Bristol-Myers Squibb and Corrona. AP has nothing to disclose. AJSO has nothing to disclose. RJD reports serving as the principal investigator on research grants from Merck and Vertex to the Brigham and Women’s Hospital for unrelated projects. SG, MB and KS are employed by Genentech. SS is consultant to WHISCON and to Aetion, a software manufacturer of which he also owns equity. SS is the principal investigator of research grants to the Brigham and Women’s Hospital from Boehringer Ingelheim.