Comparative Efficacy of Rituximab in Biologic/Targeted Synthetic DMARD-Naive Versus Exposed Rheumatoid Arthritis Patients: A Retrospective Cohort Study

Abstract

Objective: To compare the efficacy and safety of rituximab in patients with rheumatoid arthritis (RA) who were either biologic/targeted synthetic DMARD (bDMARD/tsDMARD)-naive or previously exposed. Methods: In this retrospective cohort study, 120 RA patients treated with rituximab between June 2020 and December 2023 were included. Patients were categorized as bDMARD/tsDMARD-naive (n=66) or -exposed (n=54). Clinical efficacy was assessed by change in Disease Activitity Score 28 (DAS28)-CRP and the proportion achieving low disease activity (LDA; DAS28-CRP <3.2) after treatment. Safety outcomes included infusion-related reactions (IRRs), infections, and hypogammaglobulinemia. Results: The naive group showed significantly greater improvement in disease activity (ΔDAS28-CRP: 2.5 vs. 1.9, p=0.001) and higher LDA achievement (62.1% vs. 46.2%, p=0.030) compared to the exposed group. Rates of IRRs (16.6% vs. 18.5%, p=0.820), infections (1.5% vs. 1.9%, p=0.880), and hypogammaglobulinemia were comparable between groups. Most IRRs were mild (grade 1–2); only one serious IRR occurred, with no cases requiring prolonged hospitalization. One patient in the exposed group experienced hepatitis B reactivation, managed effectively with antiviral therapy. Primary and secondary inefficacy were the most common reasons for rituximab discontinuation, with no significant differences between groups. Conclusion: Rituximab demonstrated superior efficacy in bDMARD/tsDMARD-naive RA patients, while maintaining a comparable safety profile to that in previously exposed patients. These findings support the potential benefit of using Rituximab earlier in the treatment sequence for selected RA patients.