Background/Purpose: Patients with rheumatoid arthritis (RA) often develop diabetes mellitus (DM), potentially due to aggravated systemic inflammation. Reducing inflammation with disease-modifying antirheumatic drugs (DMARD) may alter the risk of DM in RA. To date, few head-to-head comparisons of individual biologic or targeted synthetic DMARDs on the risk of DM in patients with RA are available.

Methods: We conducted a cohort study to compare DM risk in RA patients treated with different biologics or tofacitinib, using claims data from Truven Marketscan (2005-2015). RA patients free from DM at baseline were selected into one of eight exposure groups based on treatment initiation: abatacept, infliximab, adalimumab, golimumab, certolizumab, etanercept, tocilizumab, or tofacitinib. From the treatment initiation date (i.e. index date), patients were followed for the outcome of incident DM, defined as a combination of a diagnosis code and initiation of antidiabetic treatment, in an as-treated approach. To account for 60 baseline covariates including demographics, co-morbid conditions, and co-medications, we used a stabilized inverse probability (IP) weighted Cox-proportional hazard model to estimate hazard ratios (HR) of different treatments versus abatacept. All analyses were conducted separately in the following two groups: 1) new biologic initiators, who did not use any biologic DMARD in 365 days pre-index and 2) biologic switchers, who used one TNF inhibitor in 365 days pre-index and switched to a different biologic DMARD. HR estimates were then combined using inverse variance pooling.

Results: A total of 56,014 new biologic initiators and 27,152 biologic switchers with an average age of 50 years in both groups were included, of which 75% and 78% were females, respectively. Infliximab, adalimumab, and etanercept represented a large majority in both groups (86% initiators and 62% switchers), while abatacept was the most frequently used non-TNF biologic (6% initiators and 16% switchers). We observed 335 DM events in the new initiator group and 155 events in the switcher group, corresponding to incidence rates/1,000 person-years (95%CI) of 6.7 (6.0-7.5) and 7.3 (6.2-8.5), respectively. After IP weighting, a higher risk was observed among infliximab and etanercept initiators compared to abatacept initiators (Table 1). The risk was similar with all other drugs compared to abatacept.

Conclusion: In this large cohort study, we found a greater risk of incident DM in patients initiating infliximab or etanercept compared to abatacept initiators. The risk of DM was similar between other biologic or tofacitinib and abatacept initiators. Our findings corroborate observations from earlier smaller studies, which showed potentially improved insulin sensitivity and glycemic profile with abatacept.