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Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study
  1. Ajinkya Pawar1,
  2. Rishi J Desai1,
  3. Daniel H Solomon1,2,
  4. Adrian J Santiago Ortiz1,
  5. Sara Gale3,
  6. Min Bao3,
  7. Khaled Sarsour3,
  8. Sebastian Schneeweiss1,
  9. Seoyoung C Kim1,2
  1. 1 Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  2. 2 Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  3. 3 Genentech, South San Francisco, California, USA
  1. Correspondence to Dr Seoyoung C Kim, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, MA 02120, USA; sykim{at}


Objective 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.

Methods 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.

Results 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.

Conclusions 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.

  • rheumatoid arthritis
  • bacterial infections
  • serious infections
  • tocilizumab
  • tumor necrosis factor inhibitor
  • abatacept
  • biologic therapy

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  • Handling editor Josef S Smolen

  • Contributors AP had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: SCK, RJD, AP. Analysis of data: AP. Interpretation of data and drafting of the manuscript: all authors.

  • Funding This study was funded by Roche but solely conducted at the Brigham and Women’s Hospital. The funder was given the opportunity to make non-binding comments on a draft of the manuscript, but the authors retained the right of publication and to determine the final wording.

  • 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.

  • Patient consent for publication Not required.

  • Ethics approval The Institutional Review Board of the Brigham and Women’s Hospital approved the study protocol and patient privacy precautions.

  • Provenance and peer review Not commissioned; externally peer reviewed.