POS0242 THE EFFECT OF ANTIMALARIALS ON THE OVERALL SAFETY AND PERSISTENCE OF TREATMENT WITH BIOLOGIC AGENTS OR JAK INHIBITORS IN RHEUMATOID ARTHRITIS

Abstract

BackgroundAntimalarials (AM) are frequently part of the initial scheme of conventional synthetic DMARDs in the treatment of rheumatoid arthritis (RA), and have been associated with lower incidence of diabetes and better lipid profile in these patients (1). However, the role of AM in schemes involving biologic (b-) or targeted synthetic (ts-) DMARDs has been much less extensively studied. In addition, a recent large scale study (2) and a consensus article (1) casted doubt on the long-term cardiovascular safety of AM.ObjectivesTo evaluate the association of concomitant use of AM with the overall safety and survival oftreatment course among patients receiving one or multiple courses of bDMARDs or tsDMARDsMethodsBiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or tsDMARD (3). 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). A treatment course is defined as a period during which the medication scheme does not change. The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs), treatment interruption for any reason, interruption due to AEs and due to inefficacy served as secondary outcomes. Negative binomial regression with generalized estimating equations (to calculate the incidence rate ratios [ÌRRs]) and extended (frailty) Cox proportional hazards models were used for statistical analyses (both types of analyses including time-varying covariates over multiple courses of treatment).ResultsIn total, 1316 patients (2335 treatment courses, 6711 patient-years [PY]) were enrolled. The overall incidence of serious adverse events was 9.2/100 PY. AM were used over 354 courses (1254.5 PY) of therapy. The IRRs for the primary and secondary outcomes are presented in Table 1. AM were also associated with better treatment course survival (Figure 1), reducing the risk of interruption due to AEs (multivariate hazard ratio: 0.56, 95% CI: 0.39 to 0.81, P=0.002) and inefficacy (0.65, 0.48 to 0.87, P=0.003).Figure 1.Table 1.Univariate and multivariate incidence rate ratios (IRRs) of adverse events comparing use versus non-use (reference category) of antimalarials. Results are IRRs, 95% CIs, and P values.Type of adverse event (n of events)Crude analysisAdjusted covariates*Serious adverse events (617)0.60 (0.41 to 0.87), P=0.0070.51 (0.37 to 0.69), P<0.001Any adverse event (3494)0.65 (0.54 to 0.77), P<0.0010.68 (0.57 to 0.81), P<0.001Cardiovascular‡Serious (52)1.04 (0.49 to 2.20), P=0.9241.06 (0.45 to 2.50), P=0.891Total (163)0.90 (0.59 to 1.38), P=0.6420.93 (0.59 to 1.45), P=0.737InfectionsSerious (277)0.78 (0.44 to 1.39), P=0.4040.53 (0.34 to 0.83), P=0.006Total (1400)0.77 (0.61 to 0.98), P=0.0330.75 (0.60 to 0.94), P=0.014Hepatic‡Total (66)0.20 (0.07 to 0.64), P=0.0070.16 (0.04 to 0.57), P=0.005Glicemic control-relatedTotal (34)0.74 (0.29 to 1.92), P=0.5400.73 (0.26 to 2.00), P=0.535DyslipidemiaTotal (83)0.60 (0.31 to 1.13), P=0.1140.55 (0.28 to 1.06), P=0.074*Age, baseline DAS28, disease duration, gender, smoking, seropositivity (RF or anti-CCP), previous malignancy, interstitial lung disease, diabetes, hypertension, hypercholesterolemia, renal failure, ischemic cardiomyopathy, COPD, heart failure, concomitant use of each cs-, b-, and tsDMARDs, corticosteroids, starting year, osteoporosis, hepatitis B and C, and treatment sequence. ‡ Excluding infections.ConclusionAmong RA patients on treatment with bDMARDs or tsDMARDs, concomitant use of antimalarials reduced the incidence of serious and total AEs, including infections and hepatic AEs, and prolonged treatment course survival. No significant increase in the risk of cardiovascular AEs was observed.