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

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.

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.

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.

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).

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.