Cardiovascular Safety of Tocilizumab Versus Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis: A Multi-Database Cohort Study

Arthritis Rheumatol. 2017 Jun;69(6):1154-1164. doi: 10.1002/art.40084. Epub 2017 Apr 28.


Objective: While tocilizumab (TCZ) is known to increase low-density lipoprotein (LDL) cholesterol levels, it is unclear whether TCZ increases cardiovascular risk in patients with rheumatoid arthritis (RA). This study was undertaken to compare the cardiovascular risk associated with receiving TCZ versus tumor necrosis factor inhibitors (TNFi).

Methods: To examine comparative cardiovascular safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics, and MarketScan. All patients were required to have previously used a different TNFi, abatacept, or tofacitinib. The primary outcome measure was a composite cardiovascular end point of hospitalization for myocardial infarction or stroke. TCZ initiators were propensity score matched to TNFi initiators with a variable ratio of 1:3 within each database, controlling for >65 baseline characteristics. A fixed-effects model combined database-specific hazard ratios (HRs).

Results: We included 9,218 TCZ initiators propensity score matched to 18,810 TNFi initiators across all 3 databases. The mean age was 72 years in Medicare, 51 in PharMetrics, and 53 in MarketScan. Cardiovascular disease was present at baseline in 14.3% of TCZ initiators and 13.5% of TNFi initiators. During the study period (mean ± SD 0.9 ± 0.7 years; maximum 4.5 years), 125 composite cardiovascular events occurred, resulting in an incidence rate of 0.52 per 100 person-years for TCZ initiators and 0.59 per 100 person-years for TNFi initiators. The risk of cardiovascular events associated with TCZ use versus TNFi use was similar across all 3 databases, with a combined HR of 0.84 (95% confidence interval 0.56-1.26).

Conclusion: This multi-database population-based cohort study showed no evidence of an increased cardiovascular risk among RA patients who switched from a different biologic drug or tofacitinib to TCZ versus to a TNFi.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology*
  • Cohort Studies
  • Databases, Factual
  • Drug Substitution / adverse effects
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / epidemiology
  • Propensity Score
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / chemically induced
  • Stroke / epidemiology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


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