Malignant Neoplasms in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors, Tocilizumab, Abatacept, or Rituximab in Clinical Practice: A Nationwide Cohort Study From Sweden

JAMA Intern Med. 2017 Nov 1;177(11):1605-1612. doi: 10.1001/jamainternmed.2017.4332.


Importance: Considering the widespread and increasing use of biological immunomodulators (biological disease-modifying antirheumatic drugs [bDMARDs]) to treat chronic inflammatory conditions, and the concern that immunomodulation may alter cancer risk and progression, the limited available data on use of these therapies as used in clinical practice and cancer risks are a concern.

Objective: To assess the risk of incident malignant neoplasms in patients with rheumatoid arthritis (RA) treated with bDMARDs.

Design, setting, and participants: This was a national register-based prospective cohort study of the public health care system in Sweden from 2006 to 2015. Cohorts of patients with RA initiating treatment with tocilizumab (n = 1798), abatacept (n = 2021), and rituximab (n = 3586), a tumor necrosis factor inhibitor (TNFi) as first-ever (n = 10 782) or second-ever (n = 4347) bDMARD, a biologics-naive cohort treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (n = 46 610), and a general population comparator cohort (n = 107 491).

Exposures: Treatment with tocilizumab, abatacept, rituximab, or TNFi.

Main outcomes and measures: Outcomes included a first invasive solid or hematologic malignant neoplasm, or skin cancer. Hazard ratios were calculated using Cox-regression, adjusted for age, sex, disease and treatment characteristics, and educational level.

Results: We identified a total of 15 129 initiations of TNFi as the first or second bDMARD, 7405 initiations of other bDMARDs, and 46 610 csDMARD users. The mean age varied from 58 to 64 years, and the proportion of female patients varied from 71% to 80%, across the 7 cohorts under study. The observed numbers of events (crude incidence per 100 000 person-years) for a first invasive solid or hematologic malignant neoplasm were 50 (959) for tocilizumab, 61 (1026) for abatacept, 141 (1074) for rituximab, 478 (978) for initiators of TNFi as first bDMARD, and 169 (917) for TNFi as second bDMARD. There were no statistically significant differences between initiators of a first or second TNFi, or other bDMARDs, and bDMARD-naive RA for any of a total of 25 drug- and outcome-specific comparisons, with 1 exception (abatacept and increased risk of squamous cell skin cancer).

Conclusions and relevance: The overall risk of cancer among patients with RA initiating TNFi as first or second bDMARD, tocilizumab, abatacept, or rituximab does not differ substantially from that of biologic drug-naive, csDMARD-treated patients with RA, although altered risks for specific cancer types, or those with longer latency, cannot be excluded.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / epidemiology*
  • Prospective Studies
  • Registries
  • Risk Assessment
  • Risk Factors
  • Rituximab / therapeutic use*
  • Sweden / epidemiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Abatacept
  • tocilizumab