Rituximab Associated With Achieving No Evidence of Disease Activity in MS

A new study published in the Journal of Neuroimmune Pharmacology¹ found that patients with multiple sclerosis (MS) taking rituximab had substantial reductions in relapse activity and did not have any new lesions. Patients also had high short-term No Evidence of Disease Activity (NEDA-3) after treatment.

MS is a neurodegenerative disorder that can cause weakness, trouble walking, and numbness,² which can all affect quality of life, especially during cases of relapse and progressive disability. Rituximab is a treatment that has been used off label for use in MS.¹ This study aimed to evaluate the efficacy and safety of rituximab in patients living with MS, including both treatment-naive patients and those who were switching from other disease-modifying therapies (DMTs).

The study included patients with MS who were treated with rituximab between January 2018 and October 2025. All patients came from the Neurology Unit of Security Forces Hospital in Saudi Arabia. Patients were eligible if they had a confirmed diagnosis of MS, had completed 12 months of follow-up, and had received at least 1 full rituximab induction course. Patients with incomplete data, who had major systemic autoimmune comorbidities, or who were lost to follow up were excluded from the study. Patients were split into treatment-naive and switch groups based on their previous experience with DMTs.

Rituximab was distributed in 2 intravenous infusions of 1000 mg that were given on day 0 and day 14. Every 6 to 12 months, the patients would receive maintenance infusions given over 3 to 4 hours. Clinical assessments occurred at baseline, 6 months, and 12 months. The primary outcome was the proportion of patients who achieved NEDA-3 after 12 months. Change in annualized relapse rate (ARR) from before to after treatment acted as the secondary outcome.

There were 102 patients included in the study, who were followed up for a median (IQR) of 14 (12-16) months. A total of 47.1% were treatment naive, and 52.9% were in the switch group. Just over half (52.9%) were women, and the mean (SD) age of the cohort was 36.9 (9.8) years. The switch group had a significantly longer disease duration compared with the treatment-naive group. There were 33 patients who had comorbidities as well.

The estimated incidence rate ratio was 0.06 (95% CI, 0.03-0.12) after starting rituximab. Unadjusted mean ARR declined from 2.08 (1.36) to 0.12 (0.31) from baseline to 12 months. A total of 88.2% of the patients met the NEDA-3 criteria after 12 months without relapse, new MRI activity, or disability progression. The treatment-naive group saw 93.8% achieve NEDA-3, and the switch group saw 83.3% achieve NEDA-3. No significant difference was found between the groups when it came to odds of achieving NEDA-3.

Lower baseline ARR (adjusted OR [aOR], 0.58 per 1-relapse increase; 95% CI, 0.36-0.91) and lower baseline Expanded Disability Status Scale (aOR, 0.74; 95% CI, 0.36-0.91) were both independent predictors of NEDA-3. Rituximab was also well tolerated, with only mild adverse events reported.

There were some limitations to this study. There is a risk of selection bias due to the retrospective, single-center design. Incomplete data and unmeasured confounding were also possible. Long-term disability progression could not be measured with the 14-month median follow-up time. The assessment of treatment response was limited due to serum immunoglobulins and CD19 B-cell counts not being routinely monitored.

The authors concluded that this study showed that rituximab was associated with high rates of NEDA-3, absence of new MRI lesions, reductions in relapse activity, and short-term tolerability in patients who either switched to rituximab or who were treatment naive prior to starting treatment. “Prospective multicenter studies with longer observation periods and standardized immunologic monitoring are needed to clarify rituximab’s long-term safety and comparative effectiveness in diverse populations,” the authors wrote.

References

1. Elshony H, Almuhanna R, Al-Ghamdi A, et al. Comparative effectiveness of rituximab in treatment-naïve vs. switch patients with multiple sclerosis: a real-world retrospective study. J Neuroimmune Pharmacol. 2026;21(1):18. doi:10.1007/s11481-026-10288-9
2. Mayo Clinic Staff. Multiple sclerosis. Mayo Clinic. November 1, 2024. Accessed April 14, 2026. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269