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004 Pregnancy-related relapse in natalizumab, fingolimod and dimethyl fumarate-treated women with multiple sclerosis
  1. Wei Z Yeh1,2,
  2. Putu A Widyastuti1,
  3. Anneke Van der Walt1,2,
  4. Jim Stankovich1,
  5. Eva K Havrdova3,
  6. Dana Horakova3,
  7. Karolina Vodehnalova3,
  8. Serkan Ozakbas4,
  9. Sara Eichau5,
  10. Pierre Duquette6,
  11. Tomas Kalincik8,7,
  12. Francesco Patti9,
  13. Cavit Boz10,
  14. Murat Terzi11,
  15. Bassem Yamout12,
  16. Jeannette Lechner-Scott13,
  17. Patrizia Sola14,
  18. Olga Skibina2,
  19. Michael Barnett15,
  20. Marco Onofrj16,
  21. Maria J Sá17,
  22. Pamela McCombe18,19,
  23. Pierre Grammond20,
  24. Radek Ampapa21,
  25. Francois Grand’Maison22,
  26. Roberto Bergamaschi23,
  27. Daniele LA Spitaleri24,
  28. Vincent Van Pesch25,
  29. Elisabetta Cartechini26,
  30. Suzanne Hodgkinson27,
  31. Aysun Soysal28,
  32. Albert Saiz29,
  33. Melissa Gresle1,2,
  34. Tomas Uher3,
  35. Davide Maimone30,
  36. Recai Turkoglu31,
  37. Raymond MM Hupperts32,
  38. Maria Pia Amato33,34,
  39. Franco Granella35,
  40. Celia Oreja-Guevara36,
  41. Ayse Altintas37,
  42. Richard Macdonell38,
  43. Tamara Castillo-Trivino39,
  44. Helmut Butzkueven1,2,
  45. Raed Alroughani40,
  46. Vilija G Jokubaitis1,2 and
  47. MSBase Registry41
  1. 1Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
  2. 2Multiple Sclerosis and Neuroimmunology Unit, Department of Neurology, Alfred Health, Melbourne, VIC, Australia
  3. 3Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
  4. 4Dokuz Eylul University, Turkey
  5. 5Hospital Universitario Virgen Macarena, Spain
  6. 6CHUM – Hopital Notre Dame, Canada
  7. 7Melbourne MS Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia
  8. 8CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  9. 9Department of Medical and Surgical Sciences and Advanced Technologies; GF Ingrassia, University of Catania – AOU Policlinico-San Marco, University of Catania, Italy
  10. 10KTU Medical Faculty Farabi Hospital, Turkey
  11. 11Mayis University, Medical Faculty, Turkey
  12. 12American University of Beirut, Faculty of Medicine, Nehme and Therese Multiple Sclerosis Center, Beirut, Lebanon
  13. 13John Hunter Hospital, New Lambton Heights, NSW, Australia
  14. 14Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy
  15. 15Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia
  16. 16Univ G.d’Annunzio Chieti-Pescara, Italy
  17. 17Department of Neurology, São João Universitary Hospital Center, Porto, Portugal
  18. 18Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
  19. 19St Andrews Place, Spring Hill, QLD, Australia
  20. 20Centre de réadaptation déficience physique Chaudière-Appalache, Canada
  21. 21Nemocnice Jihlava, Czech Republic
  22. 22Neuro Rive-Sud, Canada
  23. 23IRCCS Mondino Foundation, Pavia, Italy
  24. 24AORN San Giuseppe Moscati Avellino, Italy
  25. 25Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Belgium
  26. 26Ospedale Generale Provinciale Macerata, Italy
  27. 27Liverpool Hospital, Liverpool, NSW, Australia
  28. 28Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Turkey
  29. 29Service of Neurology, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), and Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
  30. 30Centro Sclerosi Multipla, UOC Neurologia, ARNAS Garibaldi, Catania, Italy
  31. 31Haydarpasa Numune Training and Research Hospital, Turkey
  32. 32Maaslandziekenhuis, Netherlands
  33. 33Department NEUROFARBA, University of Florence, Italy
  34. 34IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
  35. 35University of Parma, Italy
  36. 36Department of Neurology, Hospital Clínico San Carlos, Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid (UCM) and IdISSC, Madrid, Spain
  37. 37Department of Neurology, Koc University School of Medicine, Turkey
  38. 38Department of Neurology, Austin Health, Heidelberg, VIC, Australia
  39. 39Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain
  40. 40Amiri Hospital, Kuwait
  41. 41MSBase Neuro-immunology Registry, Melbourne, VIC, Australia


Objective To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.

Methods Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 were included (modern cohort). Annualised relapse rates (ARR) were calculated before, during and after pregnancy. Predictors of intrapartum and early postpartum (1st3 months) relapse were determined by clustered logistic and Cox regression analyses, respectively.

Results We included 1640 pregnancies from 1452 women. Disease-modifying therapy (DMT) used in the one-year preconception included natalizumab (n=219), fingolimod (n=147), dimethyl fumarate (DMF; n=57) and low-efficacy therapies (n=845). Preconception ARR by DMT class used before conception were: natalizumab, 0.29 (95% CI 0.22-0.37); fingolimod, 0.37 (0.28-0.49); DMF, 0.24 (0.13-0.41); low-efficacy, 0.29 (0.25-0.33); and none, 0.24 (0.19-0.31). Among women who used fingolimod or natalizumab, ARR increased during pregnancy. Intrapartum ARR decreased in preconception DMF, low-efficacy or no DMT groups. 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).

Conclusion Women with MS prescribed natalizumab or fingolimod preconception had higher rates of intrapartum and postpartum relapse. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 32-34 weeks gestation, with early re-initiation after delivery is an effective option to minimise relapse risks. Strategies of DMT use have to be balanced against potential foetal/neonatal complications.

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