Optimizing rituximab dosing in multiple sclerosis: Real-world outcomes with interval extension.

BACKGROUND: Rituximab is highly effective in multiple sclerosis (MS), but optimal dosing intervals are unclear; extended interval dosing (EID) may preserve disease control while reducing treatment burden and cost. OBJECTIVE: To prospectively evaluate whether structured, progressive extension of rituximab infusion intervals after initial treatment could be implemented without an increase in disease activity, and to assess B-cell kinetics and infection risk. METHODS: In this single- centre prospective study,126 patients received 655 rituximab infusions. Initial standard (SD) and non-standard (NSD) dosing patterns reflected real-world treatment exposure and were not assigned comparative treatment arms. After initial treatment phase, eligible patients transitioned to a common structured EID protocol with progressive interval extension. Relapses, EDSS, MRI activity and NEDA-3 were evaluated; CD19/CD27 counts and infections were recorded. The EID analysis used longitudinal within-patient comparisons before and during interval extension. RESULTS: Disease activity remained low during initial treatment. Among those who transitioned, within-patient analysis showed no significant increase in clinical relapses (6.2%vs 8.3%), MRI lesions (20.0%vs 22.2%) or EDSS progression (4.2%vs 2.1%), and NEDA-3 was largely maintained. Peripheral B-cell repopulation showed substantial inter-individual variability and did not clearly predict clinical relapse. Higher baseline EDSS was independently associated with infection risk (OR 1.93). CONCLUSION: Structured extension of rituximab dosing intervals after initial treatment was feasible and was not accompanied by an apparent increase in disease activity during follow-up. These findings support further evaluation of individualized EID strategies, particularly in resource-constrained settings, but do not establish equivalence or non-inferiority to continued fixed-interval dosing.