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Introduction
Relapsing-remitting multiple sclerosis (RR-MS) is a chronic, disabling disease that predominantly affects women of childbearing age, for whom disease-modifying therapies (DMT) must be compatible with potential pregnancy plans. Fingolimod, a sphingosine-1-phosphate receptor modulator (S1PRM) is contraindicated in pregnancy and should be discontinued 2 months before conception.1 Discontinuation is associated with MS reactivation, particularly in young patients and women.2 We therefore conducted a bicentric observational study to evaluate disease reactivation after fingolimod withdrawal for pregnancy planning and associated pregnancy outcomes.
Methods
Setting
We conducted a retrospective cohort study in two MS centres of expertise (Foundation Rothschild Hospital and Pitié-Salpêtrière Hospital, Paris, France). Inclusion criteria were as follows: (1) women with RR-MS aged≥18 years; (2) treatment with fingolimod≥6 months, discontinued for conception planning or ongoing pregnancy between January 2014 and February 2023. MS reactivations consisted in≥1 clinical relapse, defined as ‘the occurrence/recurrence/worsening of symptoms lasting≥24 hours, ending in partial or complete remission’,3 excluding fatigue and transient fever-related worsening of symptoms. Highly effective monoclonal antibodies (MAbs) included natalizumab, rituximab, ocrelizumab while platform therapies included interferons, glatiramer acetate and dimethyl fumarate.
Statistical analysis
Categorical variables were described as counts (frequencies) and compared using Fisher’s exact test; quantitative variables were described as medians (IQR) and compared using the Wilcoxon rank-sum test, using R statistical software V.3.5.2.
Data management was performed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist (https://www.strobe-statement.org/checklists/).
Results
52 patients with 66 fingolimod discontinuations were included (online supplemental figure S1). The median age at fingolimod discontinuation was 33 (29–36) years and the median duration of fingolimod treatment was 28 (16–45) …
Footnotes
Contributors LJ collected the data, performed statistical analyses, designed the figures and wrote the first draft of the manuscript. CP and MBdlM supervised the study and participated in data interpretation and writing of the manuscript. All the authors contributed to critical revision of the manuscript, have read and approved its final version. LJ is the guarantor of the study, accepts full responsibility for the work and/or the conduct of the study, has access to the data and controlled the decision to publish.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests LJ, RD and OG have no competing interests. CB-K received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities with Alexion, Biogen, Roche, Merck, Novartis and Sanofi-Genzyme, none related to the present work. EM reports research support from Biogen and ARSEP foundation and personal fees for lectures and advisory boards from Biogen, Janssen, Merck, Novartis, Roche, Sanofi, Teva, none related to the present work. CP reports personal fees from Biogen, Medday, Merck, Novartis, Roche, Sanofi-Genzyme, Teva, none related to the present work. MBdlM has served on scientific advisory boards from Alexion, Biogen, Sanofi, Merck and Novartis and received travel honoraria from Alexion and Novartis, none related to the present work.
Provenance and peer review Not commissioned; externally peer reviewed.
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