Upfront low-dose biosimilar rituximab as first biologic therapy after triple csDMARD failure in seropositive rheumatoid arthritis: a prospective real-world strategy study

Limited access to biologic disease-modifying antirheumatic drugs (bDMARDs) in resource-constrained settings influences treatment sequencing after failure of conventional synthetic DMARDs (csDMARDs). Evidence regarding upfront use of low-dose rituximab as first biologic therapy remains limited. This study aimed to evaluate the effectiveness and steroid-sparing potential of upfront low-dose biosimilar rituximab in biologic-naïve patients with seropositive rheumatoid arthritis refractory to maximally tolerated triple csDMARD therapy.

This prospective single-centre observational study included biologic-naïve anti-CCP-positive rheumatoid arthritis patients with inadequate response to ≥ 6 months of methotrexate, hydroxychloroquine, and sulfasalazine. Patients received two infusions of biosimilar rituximab (500 mg each) administered 2 weeks apart while continuing background csDMARDs. Disease activity was assessed using DAS28-ESR at baseline and weeks 2, 6, 12, and 24. Longitudinal changes were analyzed using Friedman and Wilcoxon signed-rank tests.

Seventy-five patients (88% women) were included. Mean DAS28-ESR decreased from 5.57 at baseline to 2.78 at week 24 (p < 0.001), with a median reduction of 2.7 points. Remission rates increased from 0% to 50.7% at 24 weeks. Mean tender joint count declined from 9.43 to 1.33 and swollen joint count from 4.43 to 0.37. All patients discontinued corticosteroids during follow-up. Infusion reactions were mild, and no mortality occurred.

Upfront low-dose biosimilar rituximab as first biologic therapy achieved significant and sustained disease activity reduction with high remission rates and successful steroid withdrawal, supporting a rituximab-first strategy in resource-limited public health settings.