Comparative Effectiveness of Rituximab in Treatment-Naïve vs. Switch Patients with Multiple Sclerosis: A Real-World Retrospective Study.

Abstract

BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody, is increasingly used off-label for multiple sclerosis (MS), particularly in regions where access to approved B-cell–depleting therapies is limited. This study evaluated the real-world effectiveness and safety of rituximab in treatment-naïve and switch patients at a single center in Saudi Arabia. METHODS: In this retrospective cohort study, 102 patients with MS treated with rituximab between January 2018 and October 2025 were analyzed. Patients were categorized as treatment-naïve (n = 48) or switch (n = 54). The primary endpoint was No Evidence of Disease Activity (NEDA-3) at 12 months. Secondary outcomes included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), MRI activity, and safety. Multivariable logistic regression was used to identify predictors of NEDA-3, with findings interpreted as exploratory due to the absence of correction for multiple comparisons. RESULTS: Rituximab was associated with substantial reductions in relapse activity and absence of new MRI lesions. NEDA-3 was achieved in 93.8% of treatment-naïve and 83.3% of switch patients (p = 0.60). After adjustment for age, sex, disease duration, baseline ARR, and EDSS, the difference between groups was not statistically significant (adjusted OR = 1.52; 95% CI: 0.54–4.32; p = 0.43). ARR declined significantly in both groups (p < 0.001), with all treatment-naïve patients remaining relapse-free. No new or enlarging T2 or gadolinium-enhancing lesions were observed on 12-month follow-up MRI. EDSS remained stable. Rituximab was generally well tolerated: mild infusion reactions occurred in 3 patients (2.9%), and 3 mild infections were documented (all in the switch group). However, serum immunoglobulins were not routinely monitored, limiting assessment of infection risk related to humoral immunosuppression. Lower baseline ARR independently predicted NEDA-3 achievement (adjusted OR = 0.58 per additional relapse; 95% CI: 0.36–0.91; p = 0.02). CONCLUSION: In this single-center Saudi cohort, rituximab was associated with high short-term NEDA-3 rates and acceptable tolerability in both treatment-naïve and switch patients. A baseline ARR > 2.5 relapses/year may identify individuals at higher risk of treatment non-response. Given the retrospective design, single-center setting, short follow-up (median 14 months), and lack of immunoglobulin monitoring, findings should be interpreted cautiously. Prospective multicenter studies with standardized immune monitoring and longer follow-up are needed to confirm long-term safety and effectiveness. REGISTRATION: The study was approved by the Institutional Review Board of Security Forces Hospital, Makkah (IRB #0749-081024; HAP-02-K-052), with waiver of informed consent.