OP0137 CHALLENGING THE DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: COMPARATIVE ANALYSIS OF CLINICAL EFFICACY AND DRUG RETENTION OF SUBSEQUENT BIOLOGIC AND TARGETED SYNTHETIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS
Authors: L. Šenolt, J. Zavada, K. Kusalová, J. Baranová, P. Horak, T. Soukup, D. Suchý, R. Horváth, T. Philipp, P. Nemec, O. Sglunda, G. Nagy, J. Vencovský, K. Pavelka
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> A substantial number of patients with rheumatoid arthritis (RA) continue to experience symptoms despite receiving treatment with biologic (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs). This specific group of patients has recently been defined by EULAR as "difficult-to-treat (D2T)" RA [1]. However, determining the optimal approach for the treatment of D2T RA remains a challenge [2]. <h3>Objectives:</h3> Therefore, we conducted a comparative analysis, evaluating the clinical efficacy and drug retention of different b/tsDMARDs initiated in patients with D2T RA. <h3>Methods:</h3> A cohort of patients treated for RA in the Czech ATTRA biological registry was used to evaluated the subsequent disease course following initiation of subsequent b/tsDMARD in patients fulfilling the EULAR defined D2T RA. Simplified Disease Activity Index (SDAI) and state of remission/low disease activity (LDA) attainment were compared. Drug retention was evaluated using the Kaplan–Meier method, with assessments made at three, six, and 12 months. The results were expressed as medians along with their corresponding 95% confidence intervals (CI). Continuous variables were described by the median along with the 5th and 95th percentiles. <h3>Results:</h3> Out of the 8,493 patients, 939 (11%) met the EULAR definition of D2T RA. From this cohort, 642 individuals, who had complete data and initiated a subsequent b/tsDMARD after October 2007 and before January 2023, were included in the study. The majority of patients were female (84.7%), with a median age of 56 (34; 74) years. 64.8% of patients were receiving concomitant conventional synthetic DMARDs, and 60.4% were on glucocorticoids. A significant proportion of patients initiated non-TNFi therapy (n=406), with 147 patients initiating IL-6Ri, 133 JAKi, 71 rituximab (RTX), and 55 abatacept (ABA). At month six, SDAI remission/LDA rates were 58.9% (JAKi), 57.5% (RTX), 54.9% (IL-6Ri), 54.4% (TNFi), and 32.2% (ABA) (<b>Figure 1a</b>). The 12-month drug retention on the subsequent b/tsDMARD was 90.1 (83.5; 97.3) for RTX, 68.6 (61.5; 76.6) for anti-IL-6Ri, 67.5 (59.9; 76.0) for JAKi, 59.5 (47.8; 74.2) for ABA, and 58.8 (52.8; 65.4) for TNFi (<b>Figure 1b</b>). The highest treatment retention was observed with RTX, while TNFi showed the shortest treatment retention (median (95% CI) was 71.6 (49.8; NA) vs. 18.4 (14.7; 25.2) months; p&lt; 0.001). 41.1% of patients experienced loss of efficacy, 23.9% had primary failure, and 14.1% discontinued the subsequent treatment due to adverse events. <h3>Conclusion:</h3> More than half of the patients who initiated subsequent treatment with JAKi, RTX, IL-6Ri, or TNFi after meeting the D2T RA definition, but approximately one-third with ABA, achieved either remission or low disease activity within six months and maintained consistent drug retention for two years. The longest retention on treatment was observed with RTX. In this descriptive analysis, adjustments were not made for baseline parameters that could potentially impact the observed effectiveness outcomes. <h3>REFERENCES:</h3> [1] Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35. [2] Nagy G, et al. EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2022 Jan;81(1):20-33. <h3>Acknowledgements:</h3> Supported by projects NU23-10-00434 and 00023728 of Ministry of Health, CZ. <h3>Disclosure of Interests:</h3> <b>None declared.</b>