Background/Purpose: While tocilizumab (TCZ) may increase serum lipid levels, recent studies do not suggest an increased cardiovascular (CV) risk associated with TCZ use compared to TNF inhibitors in patients with RA. The current study examined comparative CV safety of TCZ versus abatacept in RA patients.

Methods: We conducted a cohort study using data from 3 U.S. healthcare claims databases – Medicare Parts A/B/D (2010-13), ‘IMS’ PharMetrics Plus (2011-2014) or Truven ‘MarketScan’ (2011-6/2015). Adults aged ≥18 years with RA who newly started TCZ or abatacept entered the cohort on the day of their first use of TCZ or abatacept. All patients had ≥12 month continuous enrollment free of TCZ and abatacept use before cohort entry. The primary outcome was a composite CV endpoint of hospitalization of any length for myocardial infarction (MI) and stroke based on claims-based algorithms (PPV>94%). Secondary outcomes were hospitalization for MI, stroke, coronary revascularization, heart failure and all-cause mortality. For the primary as-treated analysis, follow-up time started the day after cohort entry and ended on treatment discontinuation, outcome occurrence, disenrollment, death, or the end of study period. We estimated a propensity score (PS) to control for >60 potential confounders including demographics, prior DMARD use, comorbidities, medications, and healthcare utilization. TCZ starters were PS-matched to abatacept starters with a variable ratio of 1:3 within each database. We estimated incidence rates (IR) of composite CV events in the TCZ group compared to the abatacept group separately in each database. Hazard ratios (HR) from the 3 PS-matched cohorts were combined by an inverse variance-weighted, fixed-effects model.

Results: We included a total of 6,237 TCZ starters PS-matched to 14,685 abatacept starters in all three databases. Mean age (in years) was 72 in Medicare, 51 in IMS and 53 in MarketScan. At baseline, 73% (Medicare), 70% (IMS) and 62% (MarketScan) of TCZ or abatacept patients used methotrexate. In the as-treated analysis, the median follow-up time varied between 175 days (MarketScan) to 183 days (IMS) in the TCZ group and 193 days (MarketScan) to 209 days (Medicare) in the abatacept group.  A total of 32 CV events occurred in TCZ starters and 112 events in abatacept starters across the three databases. The IR of the primary composite CV events per 100 person-years ranged from 0.37 (IMS) to 1.64 (Medicare) in the TCZ group and from 0.59 (IMS) to 1.69 (Medicare) in the abatacept group. The risk of the primary composite CV events was similar between the two groups across all three databases (Table), with a combined HR of 0.82 (95%CI 0.55-1.22) in TCZ initiators versus abatacept initiators.  Analyses on secondary outcomes showed similar results.

Conclusion: This large multi-database cohort study found no increase in the risk of CV events in patients with RA who newly start TCZ versus abatacept.