POS0650 THE IMPACT OF OLD AGE ON THE PERSISTENCE AND SAFETY OF TREATMENT WITH BIOLOGIC AGENTS OR JAK INHIBITORS IN RHEUMATOID ARTHRITIS

Abstract

BackgroundThe effect of age on persistence and safety of treatment with biologic disease modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis has been a subject to research interest. Two recently published studies did not observe significantly different survival of treatment with bDMARDs among older age (≥ 65 years) individuals (1,2); incidence of serious adverse events was higher in these patients (2).Objectivesto evaluate association of the age with treatment survival and overall safety among patients receiving one or multiple courses of bDMARDs or targeted synthetic (ts-) DMARDs.MethodsBiobadaBrasil 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 necessarily involving a bDMARD or tsDMARD (latest date, Nov 19, 2019). Treatment course is defined as a period during which the medication scheme does not change, except for dose adjustments. Primary outcome was the incidence treatment interruption for any reason (except for pregnancy or disease remission), while interruption due to adverse events (AEs; including death) and due to inefficacy served as secondary outcomes. Incidence of serious adverse events (SAEs) also served as a secondary outcome. Extended (frailty) multivariate Cox proportional hazards models and negative binomial regression with generalized estimating equations (to calculate incidence rate ratios [IRRs]) 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, 6508 patient-years [PY]) were enrolled. Of these, 160 patients (643 PY; 237 treatment courses) were ≥ 65 years old, mean age at starting treatment = 71 ± 5 yrs (84% female). Old age was not significantly associated with treatment interruption for any reason, but presented higher risk of interruption due to adverse events (after multivariate adjustment) and lower risk of stopping because of inefficacy (see Table 1). Older patients presented higher incidence of SAEs than younger ones (16.0 vs 8.4/100 PY, respectively; multivariate IRR: 2.06, 95% CI: 1.51 to 2.80, P<0.001). Among old patients, tocilizumab (HR: 2.73, 95% CI: 1.13 to 6.64, P=0.026), etanercept (2.13, 1.12 to 4.07, P=0.022), and infliximab (2.39, 1.19 to 4.79, P=0.014) presented higher risk of treatment termination as compared with adalimumab. In this subgroup (age ≥65 yrs), there was no significant difference in the risk of SAEs between different bDMARDs/tsDMARDs.Table 1.Univariate and multivariate hazard ratios (HRs) of interruption of treatment course comparing older (≥65 years) versus younger patients (reference category). Results are HRs, 95% CIs, and P values.Cause of interruption (n of events)Crude analysisAdjusted covariates*Interruption - any reason (1321)0.96 (0.75 to 1.23), P=0.7601.09 (0.82 to 1.43), P=0.550Interruption - adverse events (368)1.33 (0.75 to 0.89), P=0.1601.59 (1.07 to 2.35), P=0.020Interruption - inefficacy (680)0.56 (0.39 to 0.80), P=0.0020.57 (0.38 to 0.87), P=0.009* Age, baseline DAS28, disease duration, gender, smoking, 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,C, treatment sequence.ConclusionThe overall risk of treatment interruption with biologic or targeted synthetic DMARDs is not higher in older patients. Higher risk of interruption due to AE was balanced by a lower risk of stopping treatment due to inefficacy. Older patients had a higher incidence of SAEs.