AB0643 DRUG SURVIVAL AND PREDICTOR FACTORS FOR DISCONTINUATION OF FIRST-LINE BIOLOGIC THERAPY: DATA FROM A REAL-WORLD SINGLE CENTER STUDY
Authors: O. Katsouli, P. Orfanos, V. Lainis, P. G. Vlachoyiannopoulos
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Although the introduction of biologic Disease-Modifying Antirheumatic Drugs (bDMARDs) has fundamentally changed the treatment of Rheumatoid Arthritis (RA), the lack of sufficient comparative studies, makes the choice of the first bDMARD a matter of "trial-and-error", leading to patients being exposed to drugs that either do not respond or have unnecessary side effects [1]. Identifying factors associated with longer drug survival and thus better outcomes is crucial [2]. <h3>Objectives:</h3> To evaluate drug survival of first bDMARD in a real-world Greek RA cohort and to determine factors that influence drug retention rates and should be considered when initiating such therapies. <h3>Methods:</h3> This retrospective study included 724 patients with RA from the record of Pathophysiology Department of General Hospital of Athens "LAIKO", who received at least one dose of their first bDMARD. Baseline demographic, clinical data and autoantibody status (Rheumatoid factor [RF], Anti-citrullinated antibodies [ACPA]) were collected. Patients were stratified according to bDMARD type, as anti-Tumor Necrosis Factor (anti-TNF, n=622) and non-anti-TNF (n=102) group, and whether an event occurred (n=410) or not (n=314). The time period between the bDMARD initiation date and the event was defined as drug survival time. Drug retention probability curves were calculated by the Kaplan-Meier method. Chi-square and t-tests were performed to determine significant differences between the groups. Significance was set at p &lt; 0.05. <h3>Results:</h3> Study population was predominantly female (79%) with a median age at the time of diagnosis 48.6 ± 15.7 years. More than half of the patients were RF (+) and/or ACPA (+), with calculated DAS28-ESR at baseline 4.9 ± 1.5. The most frequently used first-line anti-TNFs were Etanercept (ETN, n=261), Infliximab (INF, n=177) and Adalimumab (ADA, n=148) and non-anti-TNFs were Rituximab (RTX, n=40), Anakinra (n=29) and Tocilizumab (n=10). The median duration of treatment with the first bDMARD was 61 months (Q1:18, Q3:125). At 100 months, the drug survival rates for RTX, ETN, ADA and IFX were 57%, 43.7%, 37.5% and 14.1%, respectively (Figure 1). Relative to INF, the estimated incidence rate ratio (IRR) for discontinuation of RTX, ETN and ADA were 0.35 (95% confidence interval [CI] 4.35-13.55), 0.52 (95% CI 9,42-13,65) and 0.52 (95% CI 9,05-14,23), respectively. After a follow-up of 276 months, 223 patients (54.4%) discontinued treatment due to inefficacy, 186 (45.4%) due to AEs and 1 patient due to pregnancy. However, most withdrawals (73,3%) occurred within the first 50 months of follow-up regardless of cause. Discontinuation group tended to have longer disease duration in months (23,1 ± 45,0 vs 16,6 ± 33,4, p= 0,033) and higher baseline DAS28-ESR (5,1 ±1,5 vs 4,7 ± 1,5, p &lt;0.001), more comorbidities (71,2% vs 59,4%, p= 0,001) and extra-articular manifestations (54,5% vs 38,4%, p &lt;0.001). Regarding seropositivity status and drug retention in treatment groups, we found that RF and ACPA negativity were associated with better drug retention probability (RF (+) vs RF (-), p = 0.004 and ACPA(+) vs ACPA(-), p = 0.020) (Figure 2). <h3>Conclusion:</h3> After 4 years of follow-up, only a third of patients remained on their first bDMARD, with those receiving RTX less likely to discontinue for any reason. Longer disease duration and higher disease activity at baseline, as well as more comorbidities and extra-articular manifestations were associated with early discontinuation of the first bDMARD therapy. RF and ACPA negativity predicted better drug survival. <h3>REFERENCES:</h3> [1] Favalli E.G. et al. The management of first-line biologic therapy failures in rheumatoid arthritis: current practice and future perspectives. Autoimmun. Rev. 2017;16(12):1185–1195. [2] Pascual-Ramos V, et al. Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability. Arthritis Res Ther. 2009;11(1):R26. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>