Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

Wei Zhen Yeh, Putu Ayu Widyastuti, Anneke Van Der Walt, Jim Stankovich, Eva Kubala Havrdova, Dana Horakova, Karolina Vodehnalova, Serkan Ozakbas, Sara Eichau, Pierre Pascal Duquette, Tomas Kalincik, Francesco Patti, Cavit Boz, Murat Terzi, Bassem Yamout, Jeannette Lechner-Scott, Patrizia Sola, Olga Skibina, Michael Barnett, Marco OnofrjMaria José Sá, Pamela Ann McCombe, Pierre Grammond, Radek Ampapa, Francois Grand'Maison, Roberto Bergamaschi, Daniele L.A. Spitaleri, Vincent Van Pesch, Elisabetta Cartechini, Suzanne J Hodgkinson, Aysun Soysal, Albert Saiz, Melissa M. Gresle, Tòmaš Uher, Davide Maimone, Recai Turkoglu, Raymond M.M. Hupperts, Maria Pia Amato, Franco Granella, Celia Oreja-Guevara, Ayse Altintas, Richard A L Macdonell, Tamara Castillo Triviño, Helmut Butzkueven, Raed A Alroughani, Vilija Jokubaitis, on behalf of the MSBase Study Group

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.Methods Using data from the MSBase Registry, we included pregnancies conceived after December 31, 2010, in women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.Results We included 1,998 pregnancies from 1,619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% confidence interval 0.27–0.32), fell to 0.19 (0.14–0.24) in the third trimester, and increased to 0.59 (0.51–0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28–0.49) and 0.29 (0.22–0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (odds ratio 0.76 per month [0.60–0.95], p = 0.017). DMT reinitiation with natalizumab protected against postpartum relapse (hazard ratio [HR] 0.11 [0.04–0.32], p < 0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41–0.91], p = 0.016). We found that 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum.Conclusion Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation with early reinitiation after delivery is an effective option to minimize relapse risks. Strategies of disease-modifying therapy use have to be balanced against potential fetal/neonatal complications.
Original languageEnglish
Pages (from-to)e2989-e3002
Number of pages15
JournalNeurology
Volume96
Issue number24
DOIs
Publication statusPublished - 15 Jun 2021

Keywords

  • Multiple sclerosis (MS)
  • Pregnancy
  • disease modifying therapy
  • Prognostic model

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