Clinical outcomes after switching from fingolimod to B-cell-depleting therapies in multiple sclerosis: systematic review and meta-analysis.

BACKGROUND

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system, predominantly presenting as relapsing-remitting MS. Fingolimod decreases relapse rates by lymphocyte sequestration, yet persistent activity often requires switching to B cell-depleting therapies (BCDTs) such as ocrelizumab (OCR) or rituximab (RTX). Data on outcomes after this switch remain limited.

METHODS

We searched MEDLINE, Embase, and Cochrane Library databases. Single-arm rates were pooled via weighted meta-analysis; continuous outcomes by mean differences (MD), both with 95% confidence interval (C.I.). Significance was set at P < 0.05, and heterogeneity by I.

RESULTS

Eleven retrospective cohort studies (n = 1084) of MS patients switching from fingolimod to BCDTs were included in this meta-analysis. A high relapse-free proportion after switching to BCDTs (90%; 95%C.I.: 86-94%; I = 74.2%) was observed. OCR demonstrated a relapse-free proportion of 91% (95%CI: 86-97%; I = 74.5%), while RTX had 81% (95%C.I. 74-89%; I = 26.4%). Relapses during washout occurred in 11% (95%CI: 6-17%; I = 91.9%): relapse proportion was 20% (95% CI 7-34%; I = 90.3%) after a long washout (> 4 weeks) and 0% (95% CI: 0-2%; I = 0%) after a short washout (< 4 weeks). Radiological activity-free proportion was 76% (95% CI 59-88%; I = 81.2%) overall BCDTs. Regarding Expanded Disability Status Scale, no significant change was observed after switching (MD - 0.845; 95%C.I. - 2.062-0.371; P = 0.173; I = 89.4%).

CONCLUSION

MS patients who switched from fingolimod to OCR or RTX maintained high rates of both clinical remission and radiological stability, and a washout shorter than four weeks virtually eliminated relapses-demonstrating robust efficacy for BCDTs in this subgroup.