Real-World Effectiveness of Biologic and Targeted Synthetic Therapies in Rheumatoid Arthritis: a Multicenter Study from Rheumatoid Arthritis Saudi Database (RASD).

Purpose: Rheumatoid arthritis (RA) management emphasizes treat-to-target strategies with timely escalation from conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to biologic (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) when remission or low disease activity is not achieved. Comparative real-world effectiveness evidence across advanced therapies remains limited in some settings. To compare 12-month outcomes and treatment persistence across biologic (bDMARD) and targeted synthetic DMARDs (tsDMARDs) in Saudi patients enrolled in the Rheumatoid Arthritis Saudi Database (RASD). Patients and Methods: We conducted a prospective multicenter cohort study of RASD patients receiving biologic or targeted synthetic DMARDs, with a minimum follow-up of 12 months and assessments at baseline, 3-6 months, and 12 months. Outcomes included longitudinal DAS28-CRP change, 12-month disease activity, function, fatigue, remission, and treatment persistence through 36 months. Analyses used mixed-effects, covariate-adjusted regression, ordinal regression, logistic regression, and Kaplan-Meier methods, as appropriate for each outcome. Results: We analyzed 647 treatment courses across nine advanced therapies. Disease activity improved significantly over time, with a strong overall DAS28-CRP time effect (p<0.0001), but no significant overall drug effect (p=0.327) or time-by-drug interaction (p=0.218). Model-estimated 12-month DAS28-CRP values were closely clustered across therapies, with overlapping confidence intervals and no significant pairwise differences. In adjusted 12-month analyses, DAS28-CRP, CDAI, fatigue severity, and remission were comparable across agents. Most adjusted between-drug comparisons were non-significant, except for worse HAQ category with certolizumab compared with tofacitinib (adjusted OR 2.45, 95% CI 1.12-5.37). Remission varied significantly across participating centers. Discontinuation rates were low, most commonly due to lack of efficacy, and treatment persistence did not differ significantly across therapies through 36 months (log-rank p=0.17). Conclusion: Advanced RA therapies were associated with significant disease activity improvement and minimal adjusted between-drug differences. Except for an isolated worse HAQ signal with certolizumab versus tofacitinib, outcomes were broadly comparable across agents. Center-level remission variation highlights the importance of standardized treat-to-target implementation. Trial Registration: ClinicalTrials.gov Identifier: NCT06417138.