Extended Interval Dosing of Off-Label Rituximab in Multiple Sclerosis: A Real-World Retrospective Analysis of Clinical Efficacy and Safety Publisher Pubmed



Paybast S ; Jameie M ; Tajabadi Z ; Azizmohammad Looha M ; Basti FA ; Amanollahi M ; Amani K ; Mousavi M ; Mohammadianinejad SE ; Harirchian MH
Source: Multiple Sclerosis and Related Disorders Published:2026

Abstract

Objectives: Rituximab, an anti-CD20 monoclonal antibody, is increasingly used off-label as a high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS). Given an increasing interest to extended interval dosing (EID) (6-month infusion intervals +≥ 4 weeks) regimen as a strategy to mitigate the risk of infection associated with anti-CD20s, herein we aimed to investigate the treatment outcomes of patients with MS (PwMS) receiving EID vs. standard interval dosing (SID) of rituximab. Methods: Between January 2020 and January 2022, PwMS prescribed rituximab at Imam Khomeini MS Center in Tehran, Iran, were identified. Clinician-reported data were retrospectively collected. Results: Eighty-nine PwMS (67.4% with progressive MS; mean age: 41.2 ± 10.1 years; 58.4% female) were enrolled. Fifty-two received EID (9.40 ± 1.26 month) and 37 received SID. After adjusting for covariates, there was no significant inter-group difference for disability progression (P = 0.33). Except for one patient in the EID group, all remained relapse-free for one year. CD19+ B-cell reconstitution patterns were significantly different between the two groups (P = 0.021), showing a gradual rather than rapid peripheral CD19+ B-cell repopulation in the EID group. While the overall adverse event rates were similar, patients in the EID group had a significantly lower incidence of serious infectious adverse events at both 6 months (P = 0.03) and 12 months (P = 0.04). Conclusions: In this real-world cohort, EID regimen of rituximab was associated with reduced risk of serious infections, without compromising disease control or disability progression. Further prospective studies are warranted to validate our findings. © 2026