The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis

Abstract

Objectives To test the association of use of antimalarials with the overall safety of treatment in rheumatoid arthritis (RA) patients receiving one or multiple courses of biologic (b-) DMARDs or a Janus kinase inhibitor (JAKi). Methods BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from Jan 2009 to Oct 2019, followed-up over one or multiple (up to six) courses of treatment (latest date, Nov 19, 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. Results 1316 patients (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials) were enrolled. The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49, 95% CI: 0.36–0.68, P< 0.001), total adverse events (0.68, 0.56–0.81, P< 0.001), serious infections (0.53, 0.34–0.84, P= 0.007) and total hepatic adverse events (0.21, 0.05–0.85, P= 0.028). Antimalarials were also related to better survival of treatment course (P= 0.003). There was no significant increase in the risk of cardiovascular AEs. Conclusion Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.