Wei Zhen Yeh1,2, Putu Ayu Widyastuti1, Anneke Van der Walt1,2, Jim Stankovich1, Eva Havrdova3, Dana Horakova3, Karolina Vodehnalova3, Serkan Ozakbas4, Sara Eichau5, Pierre Duquette6, Tomas Kalincik7,8, Francesco Patti9,10, Cavit Boz11, Murat Terzi12, Bassem I Yamout13, Jeannette Lechner-Scott14, Patrizia Sola15, Olga G Skibina2, Michael Barnett16, Marco Onofrj17, Maria José Sá18, Pamela Ann McCombe19, Pierre Grammond20, Radek Ampapa21, Francois Grand'Maison22, Roberto Bergamaschi23, Daniele L A Spitaleri24, Vincent Van Pesch25, Elisabetta Cartechini26, Suzanne Hodgkinson27, Aysun Soysal28, Albert Saiz29,30, Melissa Gresle1,2, Tomas Uher3, Davide Maimone31, Recai Turkoglu32, Raymond Mm Hupperts33, Maria Pia Amato34,35, Franco Granella36, Celia Oreja-Guevara37,38, Ayse Altintas39, Richard A Macdonell40, Tamara Castillo-Trivino41, Helmut Butzkueven1,2,42, Raed Alroughani43, Vilija G Jokubaitis44,2. 1. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia. 2. Department of Neurology, Alfred Health, Melbourne, Victoria, Australia. 3. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 4. Dokuz Eylul University, Turkey. 5. Hospital Universitario Virgen Macarena, Spain. 6. CHUM - Hopital Notre Dame, Canada. 7. CORe, Department of Medicine, University of Melbourne, Australia. 8. Melbourne MS Centre, Royal Melbourne Hospital, Australia. 9. Department of Medical and Surgical Sciences and Advanced Technologies. 10. GF Ingrassia, University of Catania - AOU Policlinico-San Marco, University of Catania. 11. KTU Medical Faculty Farabi Hospital, Turkey. 12. Mayis University, Medical Faculty, Turkey. 13. American University of Beirut, Faculty of Medicine, Nehme and Therese Multiple Sclerosis Center, Beirut, Lebanon. 14. John Hunter Hospital, Australia. 15. Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy. 16. Brain and Mind Centre, University of Sydney, Australia. 17. Univ G.d'Annunzio Chieti-Pescara, Italy. 18. Department of Neurology, São João Universitary Hospital Center, Porto, Portugal. 19. St Andrews Place, Australia, & Royal Brisbane and Women's Hospital, Australia. 20. Centre de réadaptation déficience physique Chaudière-Appalache, Canada. 21. Nemocnice Jihlava, Czech Republic. 22. Neuro Rive-Sud, Canada. 23. IRCCS Mondino Foundation, Pavia, Italy. 24. AORN San Giuseppe Moscati Avellino, Italy. 25. Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Belgium. 26. Ospedale Generale Provinciale Macerata, Italy. 27. Liverpool Hospital, Australia. 28. Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Turkey. 29. Service of Neurology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS). 30. Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain. 31. Centro Sclerosi Multipla, UOC Neurologia, ARNAS Garibaldi, Catania, Italy. 32. Haydarpasa Numune Training and Research Hospital, Turkey. 33. Maaslandziekenhuis, Netherlands. 34. Department NEUROFARBA, University of Florence, Italy. 35. IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy. 36. University of Parma, Italy. 37. Department of Neurology, Hospital Clínico San Carlos, Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid (UCM). 38. IdISSC, Madrid, Spain. 39. Department of Neurology, Koc University School of Medicine, Turkey. 40. Department of Neurology, Austin Health, Heidelberg, Australia. 41. Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain. 42. Box Hill Hospital, Australia. 43. Amiri Hospital, Kuwait. 44. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia vilija.jokubaitis@monash.edu.
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 31 Dec 2010 from 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 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in 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 (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (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). 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 re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.
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 31 Dec 2010 from 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 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in 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 (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (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). 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 re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.
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