Comparative Effectiveness of Rituximab in Treatment-Naïve vs. Switch Patients with Multiple Sclerosis

Background Rituximab, an anti-CD20 monoclonal antibody, is increasingly used off-label in multiple sclerosis (MS), particularly where access to approved B-cell therapies is limited. This retrospective cohort study assessed its real-world effectiveness and safety in treatment-naïve versus switch patients at a single center in Saudi Arabia. Methods We retrospectively analyzed data from 34 MS patients treated with rituximab at Security Forces Hospital, Makkah, between January 2018 and December 2024. Patients were categorized as treatment-naïve (n = 16) or treatment-switch (n = 18). Outcomes included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), MRI activity, adverse events, and no evidence of disease activity (NEDA) status at 12-month follow-up. Results Rituximab significantly reduced ARR in both groups (naïve: 1.44 ± 0.73 to 0.06 ± 0.25, p < 0.001; switch: 2.67 ± 1.46 to 0.17 ± 0.38, p < 0.001). NEDA was achieved in 93.8% of naïve and 83.3% of switch patients (p = 0.60). EDSS remained stable or improved in most cases (p = 0.94). No new T2 lesions were observed on MRI in any patient. Adverse events were minimal and manageable, with one mild infusion reaction and one case of asymptomatic lymphopenia. Post-treatment lymphocyte counts were lower in switch patients (p = 0.03), but no severe infections occurred. Conclusion In this retrospective cohort, rituximab demonstrated significant short-term efficacy in relapse reduction and disease stabilization in both treatment-naïve and switch MS patients, with a favorable safety profile. However, these findings must be interpreted cautiously due to the small sample size, retrospective design, and baseline group differences. Larger prospective studies are warranted to confirm long-term outcomes. Registration: The study protocol was approved by the Institutional Review Board (IRB) of Security Forces Hospital Makkah (SFHM), registered with the National BioMedical Ethics Committee under King Abdulaziz City for Science and Technology (Registration number: HAP-02-K-052). IRB approval number: [0749-081024], dated November 2024.