Assessing the Comparative Effect of Tocilizumab on Risk of Cardiovascular Disease among Rheumatoid Arthritis Patients Using Claims Data: A Direct Comparison among Biologic Disease-Modifying Antirheumatic Drugs

Tocilizumab is a humanized monoclonal anti-body against the interleukin-6 receptor and is effective in the treatment of rheumatoid arthritis (RA). Multiple studies have observed unfavorable changes in the lipid profile of tocilizumab-treated RA patients. Few studies have compared the cardiovascular disease (CVD) risk associated with tocilizumab to other biologic disease-modifying antirheumatic drugs (bDMARDS). Due to limitations in existing studies, the real-world association of tocilizumab with CVD risk remains uncertain. We conducted a retrospective cohort study using 2006–2015 Medicare and MarketScan claims data to assess the comparative effect of tocilizumab on CVD risk. Medicare claims data provide a unique opportunity to estimate disease burden and conduct comparative effectiveness studies with much larger sample sizes than cohorts, which require primary data collection. However, Medicare claims data lack information on cause of death. To address this limitation, we developed claims-based algorithms for identifying fatal CVD in Medicare claims data using The Reasons for Geographic and Racial Difference in Stroke (REGARDS) data linked to Medicare claims. CVD events iv and cause of death in the REGARDS study were adjudicated by two experts. Our algorithm can identify fatal CVD events with high sensitivity and specificity. Our study confirmed that tocilizumab was not associated with increased or decreased CVD risk compared to etanercept: the hazard ratio for tocilizumab compared to etanercept was 0.91 (95%CI: 0.66, 1.25). However, unlike the clinical trial, which enrolled only high-risk patients, we extended this finding to “low CVD risk” RA patients. We also showed that tocilizumab was not associated with increased or decreased CVD risk compared to abatacept or rituximab. We further showed that tocilizumab was associated with reduced CVD risk when compared to a pooled TNFi group. This is most likely due to slightly increased CVD risk associated with infliximab. We also conducted a retrospective cohort study using Medicare claims data to assess the effect of methotrexate on CVD risk among bDMARDS users and found that methotrexate was associated with an overall 27% (95%CI: 18–35%) reduction in CVD risk. The hazard ratio for tocilizumab concomitantly with methotrexate compared to tocilizumab only was 0.66 (95%CI: 0.40–1.09)