Maternal and fetal outcomes in an Italian multicentric cohort of women with multiple sclerosis exposed to dimethyl fumarate during pregnancy.

BACKGROUND

Evidence on the impact of dimethyl fumarate (DMF) during pregnancy in women with multiple sclerosis (MS) is limited.

OBJECTIVES

To investigate disease activity and pregnancy outcomes in a retrospective cohort of women exposed to DMF in early pregnancy.

METHODS

Women discontinuing DMF after pregnancy confirmation were identified from 29 Italian MS Centers. Disease activity 12 months before conception, during pregnancy, and 12 months postpartum were recorded, exploring reactivation predictors. Pregnancy and fetal outcomes were assessed.

RESULTS

The study analyzed 137 pregnancies (12 pregnancy losses, 125 live births) from 137 women (mean age 32.9 ± 4.7 years), discontinuing DMF within a median (interquartile range (IQR)) interval of 4.9 (3.7-5.7) weeks from conception. In live birth pregnancies, annualized relapse rate (ARR) significantly decreased during pregnancy (ARR = 0.07, 95% confidence interval (CI): 0.03-0.14,

CONCLUSION

DMF discontinuation does not increase relapse risk during pregnancy. Early therapy restart prevents postpartum relapses. Early DMF exposure shows no adverse fetal outcomes.

Déclaration de conflit d'intérêts

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.L. received travel funding from Biogen, Merck-Serono, Sanofi-Genzyme, Teva, Bristol-Myers Squibb, Mylan, Novartis, Roche, Horizon, Alexion speaking or consultation fees from Sanofi-Genzyme, Merck-Serono, Teva, Biogen, Roche, Novartis, Bristol-Myers Squibb, Bayer-Schering. S.B. received travel funding from Biogen and Bristol-Myers Squibb. F.B. reported receiving teaching honoraria from Novartis and personal fees from Eisai, Biogen, and Chiesi outside the submitted work. M.P.A. has received research grants honoraria as a speaker and member of Advisory Boards from Biogen, Bayer, Novartis, Roche, Teva, Sanofi-Genzyme, Merck, Roche Celgene BMS, Janssen, Horizon. S.B. speaker honoraria and/or travel/congress grant from: Novartis, Merck-Serono, Alexion, BMS, Biogen, Roche, Janssen-Cilag. Research grant from Roche. G.B. received honoraria for speaking or consultation fee from Almirall, Biogen, Merck, Novartis, Sanofi, Teva, Roche. M.B. declares fees from Biogen, Sanofi-Genzyme, Roche, and Novartis. S.B. has been founded for advisory board, academic purposes and speech honoraria by Genzyme, Roche, Biogen, Merck-Serono, Novartis and Almirall. P.C. received honoraria for speaking and/or for consultancy and support for participation to scientific congresses from Almirall, Biogen, Merck-Serono, Novartis, Sanofi-Genzyme, Roche, Teva, Alexion, Celgene BMS, Janssen, Horizon. M.C. received personal compensations for public speaking from Novartis, Sanofi-Genzyme, Teva and consulting fees from Roche and Zambon. D.C. is an Advisory Board member of Almirall, Bayer-Schering, Biogen, GW Pharmaceutical, Merck-Serono, Novartis, Roche, Sanofi-Genzyme and Teva and received honoraria for speaking or consultation fee from Almirall, Bayer-Schering, Biogen, GW Pharmaceuticals, Merck-Serono, Novartis, Roche, Sanofi-Genzyme and Teva. He is also the principal investigator in clinical trials for Bayer-Schering, Biogen, Merck-Serono, Novartis, Roche, Sanofi-Genzyme. E.C. received travel grant, speaker fee and consultancy from Biogen Idec, Teva, Genzyme, Merck-Serono, Novartis, Roche and Admirall. A.C. has served on scientific advisory boards for Merck-Serono, Sanofi-Genzyme, Biogen, Novartis, Almirall. She has received institutional research support from Roche and Biogen. A.C. received speaker honoraria from Biogen, Sanofi-Genzyme, Teva and travel grants from Biogen, Merck, Sanofi-Genzyme, Teva; advisory boards member honoraria from Biogen, Merck, Novartis, Teva. E.D.A. received speaking honoraria from Biogen, Merck-Serono, Novartis, Sanofi-Genzyme, Bayer-Schering. M.D.F. participated on advisory boards and steering committees for and received speaker or writing honoraria, research support and funding for traveling from Alexion, BMS, Bayer, Biogen Idec, Genzyme, Horizon, Merck, Mylan, Novartis, Roche, Siemens Healthineers, Teva and Viatris. R.D. received honoraria as a speaker and member of advisory boards by: Merck-Serono, Roche, Novartis and travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme, Roche, Merck-Serono. R.F. has received consulting fees and honoraria for advisory boards from Biogen Idec, Merck-Serono, Novartis, Roche, and TEVA. E.F. has received travel grants from Biogen, Merck, Sanofi-Genzyme, Novartis, and Roche. M.F. is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Associate Editor of Radiology, and Associate Editor of Neurological Sciences; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and Teva; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and Fondazione Italiana di Ricerca per la SLA. M.F. published opinions in a medical journal on other pharmaceuticals and received financial support for travel and meeting attendance from Biogen, Merck, Roche, Sanofi-Genzyme and Novartis. A.G. received honoraria for speaking and travel grants from Merck, Genzyme, Teva, Mylan, Roche and Novartis. F.G. received research funding from Sanofi-Genzyme and Biogen, fees for advisory boards and speaking honoraria from Biogen, Novartis, Sanofi-Genzyme, Merck-Serono and Roche, travel funding from Biogen, Sanofi-Genzyme, Merck-Serono, and Roche. A.I. received consulting fees from Janssen. R.L. received personal compensations for speaking or consultancy from Biogen, BMS, Sanofi, Merck, Novartis, Roche and Alexion. L.L. received travel grant, speaker fee and consultancy from Biogen Idec, Teva, Sanofi-Genzyme, Merck-Serono, Novartis, Roche and Almirall. M.L. has served on advisory boards and/or has received travel grants and/or speaker honoraria from Merck, Biogen, Almirall, Novartis, and Sanofi-Genzyme. G.L. received speaker honoraria and/or consultancy from Biogen, Teva, Genzyme, Merck, Novartis, Almirall, Roche. G.M. received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme, Bristol-Myers Squibb, Horizon, Roche, Merck-Serono. M.M. received compensation for consulting services, speaking activities, and participation in advisory board from Alexion, Almirall, Bayer, Biogen, Bristol-Myers Squibb, Celgene, CSL Behring, Novartis, Roche, Sanofi-Genzyme, Janssen, Merck-Serono, and Viatris; he received research support from Biogen, Merck-Serono, Novartis, and Roche. L.M. received honoraria for speaking activity at scientific meetings and/or advisory boards from Biogen, Merck-Serono, Sanofi-Genzyme, Novartis, Roche, Alexion, Celgene, Almirall. G.N. received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme, Horizon, Roche, Merck-Serono. F.P. reports grants from Biogen, grants from Merck, grants from FISM, grants from Onlus association, grants from University of Catania, personal fees from Almirall, personal fees from Bayer, personal fees from Biogen, personal fees from Merck, personal fees from Roche, personal fees from Sanofi, personal fees from TEVA, outside the submitted work. P.R. received travel expenses or honoraria for speaking or participating to advisory board by: Biogen idec, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi. S.R. has received travel expenses or honoraria for speaking or participating to advisory boardby: Biogen idec, Merck, Sanofi-Genzyme, Novartis, Teva, Roche, Bristol-Myers squibb. G.S. received travel expenses by Roche and Novartis. E.S. received speaker honoraria and/or consultancy from Biogen, Teva, Genzyme, Merck, Novartis, Almirall, and Roche. L.S. received congress grants from Merck-Serono, Biogen and board grants from Norvartis, Merck-Serono. M.P.S. has received consulting fees from Biogen, GeNeuro, MedDay, Merck, Novartis, Roche, Sanofi and Teva. V.T. has received honoraria, travel grants and research grant support from FISM, Italian Ministry of Health, Alexion, Roche, Merck, Biogen, Novartis, Viatris, Bristol-Myers Squibb, Almirall, Horizon, Lundbeck, Sanofi, Janssen. D.V. has received travel grants and honoraria for Advisory Boards from Novartis, Roche, Teva, Sanofi-Genzyme, Merck-Serono, and Almirall. G.A.M. received ravel funding, speaking or consultation fees from Almirall, Bayer-Schering, Biogen, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Mylan, Bristol Mayers Squibb and research grants from Roche and Biogen. The remaining authors have nothing to disclose.