POS0676 SURVIVAL OF THE FIRST COURSE OF BIOLOGIC OR JAK INHIBITOR IN RHEUMATOID ARTHRITIS: ASSOCIATION WITH THE CHOICE OF AGENT AND CONCOMITANT CONVENTIONAL SYNTHETIC DMARDS
Authors: M. Bredemeier, A. Duarte, M. Pinheiro, B. Stadler, J. C. Macieira, R. Ranza, J. Miranda, V. Valim, G. Castro, M. Bertolo, M. D. F. Sauma, V. Fernandes, A. Medeiros, R. Botelho, C. Brenol, D. Negrão Gonçalo Dias, H. Carvalho, S. Studart, G. Da Rocha Castelar Pinheiro, L. Rocha, I. Pereira, M. Ohira Gazzeta, A. Maria Kakehasi, P. Louzada, A. L. S. Hayata, F. Pina, C. Lupo, L. Balarini, I. Silveira, S. Kowalski, D. Titton, R. Chakr, A. Ranzolin, I. Laurindo, R. Xavier
Journal: Annals of the Rheumatic Diseases (2021)

Background: After failure of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in the therapy of rheumatoid arthritis (RA), treatment may be escalated to biologic (bDMARDs) or JAK inhibitors (JAKi) (1). Analysis of drug survival can provide useful information on the effectiveness of these therapeutic schemes. Objectives: to evaluate the association of the choice of therapeutic agent with the survival of treatment course in RA patients receiving their first bDMARD or JAKi. Methods: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients starting their first bDMARD/JAKi (2). This analysis includes RA patients recruited from Jan 2009 to Oct 2019, followed-up over the first course of treatment with a bDMARD/JAKi until censoring (latest date, Nov 19, 2019) or occurrence of the outcome of interest. A treatment course is defined as a period during which the medication scheme does not change, except for dose adjustments. The primary outcome was the interruption of treatment course for any reason (except for pregnancy or disease remission); interruption of treatment due to adverse events (AEs) or death and due to inefficacy served as secondary outcomes. Multivariate Cox proportional hazards models were used for analyses. Results: In total, 1177 patients (3800 patient-years [PY]) were enrolled. The overall incidence of treatment interruption was 17.5/100 PY. Adalimumab was the most frequently prescribed agent, followed by infliximab (n= 267). The hazards ratios (HR) of the primary and secondary outcomes are presented in Table 1. Figure 1 compares the survival of treatment curves of different bDMARDs/JAKi. Table 1. Hazard ratios (HR) of interruption of therapy course of each therapeutic agent (the reference category for bDMARDs/ JAKi is infliximab). Results are HR, 95% CIs, and P values*. Agent (number of patients) Interruption for any reason (665 events) Interruption due to adverse events or death (196 events) Interruption due to inefficacy (319 events) Adalimumab (354) 0.83 (0.68 to 1.01), P= 0.062 0.68 (0.48 to 0.96), P=0.029 1.08 (0.80 to 1.44), P=0.621 Etanercept (257) 0.81 (0.66 to 1.01), P=0.063 0.56 (0.37 to 0.83), P=0.004 0.93 (0.68 to 1.29), P=0.674 Certolizumab (80) 0.74 (0.47 to 1.16), P=0.185 0.33 (0.13 to 0.86), P=0.024 1.32 (0.74 to 2.35), P=0.350 Golimumab (53) 0.86 (0.53 to 1.38), P=0.530 0.46 (0.18 to 1.19), P=0.111 1.07 (0.53 to 2.15), P=0.849 JAKi (tofacitinib) (59) 0.54 (0.30 to 0.99), P=0.047 0.19 (0.04 to 0.82), P=0.026 0.89 (0.41 to 1.96), P=0.779 Rituximab (48) 0.87 (0.55 to 1.37), P=0.540 0.48 (0.20 to 1.18), P=0.109 0.58 (0.26 to 1.34), P=0.205 Abatacept (30) 0.52 (0.25 to 1.07), P=0.077 0.46 (0.14 to 1.56), P=0.215 0.46 (0.14 to 1.52), P=0.203 Tocilizumab (29) 0.29 (0.14 to 0.63), P=0.002 0.40 (0.12 to 1.30), P=0.126 0.28 (0.09 to 0.90), P=0.033 Methotrexate (792) 0.95 (0.79 to 1.14), P=0.561 0.86 (0.62 to 1.19), P=0.362 0.98 (0.75 to 1.28), P=0.860 Leflunomide (497) 1.17 (0.99 to 1.39), P=0.061 1.44 (1.06 to 1.96), P=0.020 1.02 (0.80 to 1.30), P=0.856 Sulfasalazine (48) 1.18 (0.80 to 1.75), P=0.401 1.94 (1.07 to 3.54), P=0.030 0.85 (0.45 to 1.59), P=0.605 Antimalarials (230) 0.80 (0.65 to 0.98), P=0.027 0.67 (0.45 to 0.99), P=0.043 0.67 (0.50 to 0.92), P=0.011 * All tests adjusted for other variables presented in the table and for age, baseline DAS28, disease duration, gender, smoking, seropositivity (RF/anti-CCP), previous malignancy, diabetes, hypertension, hypercholesterolemia, renal failure, ischemic cardiomyopathy, COPD, heart failure, use of corticosteroids, starting year, hypercholesterolemia, osteoporosis, hepatitis B and C. Conclusion: In our study, infliximab was related to an overall higher hazard of treatment course interruption than tolicizumab and tofacitinib, and higher hazard of interruption due to AEs than most other anti-TNF agents and tofacitinib. Maintaining antimalarials in patients receiving advanced therapies for RA may reduce interruption of treatment due to inefficacy and AEs. Disclosure of Interests: None declared