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Sustained Low Relapse Rate With Highly Variable B-Cell Repopulation Dynamics With Extended Rituximab Dosing Intervals
Chiara Starvaggi Cucuzza1, Elisa Longinetti1, Nicolas Ruffin1
1From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Extending rituximab dosing intervals for relapsing-remitting multiple sclerosis (RRMS) did not increase disease activity. This approach may mitigate infection risks without compromising treatment efficacy in RRMS patients.
Area of Science:
- Neurology
- Immunology
- Pharmacology
Background:
- B cell-depleting therapies like rituximab are effective for relapsing-remitting multiple sclerosis (RRMS).
- However, these therapies increase infection risk and blunt vaccine responses.
- Extended dosing intervals are being explored to mitigate these side effects.
Purpose of the Study:
- To evaluate clinical and neuroradiologic disease activity in RRMS patients on extended rituximab dosing intervals.
- To assess B-cell repopulation dynamics following extended rituximab dosing.
Main Methods:
- Prospective observational study of RRMS patients receiving rituximab.
- Analysis of 3,904 dose intervals in 718 patients, stratified by time since last infusion (<8, 8-12, 12-18, ≥18 months).
- Cox regression used to calculate hazard ratios for relapse and contrast-enhancing lesions.
Main Results:
- No significant increase in clinical relapse or MRI-detected disease activity was observed with extended dosing intervals (≥8 months).
- Relapse rates were low across all interval groups, with only 4 relapses occurring >8 months post-infusion.
- B-cell repopulation varied, with median total B-cells reaching normal levels by 12 months and memory B-cells by 16 months.
Conclusions:
- Extended rituximab dosing intervals appear safe regarding disease activity in RRMS.
- This strategy may offer a way to reduce adverse events without compromising treatment effectiveness.
- Further research is needed on B-cell dynamics and adverse event risks.
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