Principal Investigator: Øivind Torkildsen
B-cell depletion therapies are highly effective in relapsing-remitting MS (RRMS). Rituximab seems to have a similar efficacy and safety profile to ocrelizumab, but data on optimal dosing is limited and largely based on various off-label regimens. The most commonly used dosing regimen in Norway is a single starting dose of 1000 mg intravenous infusion, followed by maintenance doses of 500 mg every 6 months indefinitely. Rituximab is well tolerated and the frequency of reported side effects is low, but infections, neutropenia and hypogammaglobinaemia occur in some patients and can be associated with serious adverse events or therapy discontinuation. Real world data indicate that B-cells may be depleted for a longer period than the current dosing interval, possibly up to 12 months or more, and prolonged dose intervals (i.e. postponed doses due to intercurrent illness or pregnancy planning) seems safe.
Based on these observations, we aim to investigate if extended dosing intervals from 6 to 12 months is safe and effective in RRMS. We plan to enrol clinical stable patients that have received a standard dose of rituximab at 6 months intervals for 1-3 years. Patients will be randomized into maintenance therapy (rituximab 500 mg) groups of either 6 month or 12 month dosing intervals. Participants will be closely monitored by clinical evaluation (including standardized scoring), magnetic resonance imaging (MRI) and immune cell phenotyping, including CD19 and CD27 B-cell monitoring.
The objectives of the trial are to evaluate efficacy of extended dosing (12 months) interval of rituximab versus todays’ standard (6 months) interval, and to compare safety in the two dosing regimens including frequency of neutropenia, hypogammaglobinaemia and infections. We will also evaluate and compare vaccine response in the two dosing regimens.
The primary endpoint of the study is the proportion of patients with no evidence of disease activity (NEDA) after 2 years.
Currently, the study protocol is under preparation for submission to the Regional Committees for Medical and Health Research Ethics Western Norway, and the Norwegian Medicines Agency autumn 2020. Estimated study start; Q1, 2021