Pragnancy and multiple sclerosis from a neurologist’s point of view

Czech version

Authors: P. Hradílek ¹; E. Meluzínová ²; I. Kovářová ³
Authors‘ workplace: Neurologická klinika FN Ostrava ¹; Neurologická klinika 2. LF UK a FN Motol, Praha ²; Neurologická klinika 1. LF UK a VFN, Praha ³
Published in: Cesk Slov Neurol N 2018; 81(6): 647-652
Category: Review Article
doi: https://doi.org/10.14735/amcsnn2018647

Overview

Young women with reproduction potential form a major population among MS patients. The treatment of their disease should be managed regarding to possible occurrence of pregnancy. This should be planned, only thus the neurologist can adjust the treatment, so that the foetus would not be endangered by increased risk of abnormal evolution. The paper deals with the risk of individual disease modifying drugs (DMD) used for MS in early pregnancy and also during breastfeeding and brings practical recommendations for individual situations.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Sources

1. Ziemssen T, Neuhaus O, Hohlfeld R. Risk-benefit assessment of glatiramer acetate in multiple sclerosis. Drug Safety 2001; 24(13): 979–990. doi: 10.2165/ 00002018-200124130-00005.

2. Cree B. Update on reproductive safety of current and emerging disease modifying therapies for multiple sclerosis. Mult Scler 2013; 19(7): 835–843. doi: 10.1177/ 1352458512471880.

3. Thöne J, Thiel S, Gold R et al. Treatment of multiple sclerosis during pregnancy – safety considerations. Expert Opin Drug Saf 2017; 16(5): 523–534. doi: 10.1080/ 14740338.2017.1311321.

4. Lu E, Wang BW, Guimond C et al. Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review. Neurology 2012; 79(11): 1130–1135. doi: 10.1212/ WNL.0b013e3182698c64.

5. Patti F, Cavallaro T, Lo Fermo S et al. Is in utero early exposure to interferon beta a risk factor for pregnancy outcomes in multiple sclerosis? J Neurol 2008; 255(8): 1250–1253. doi: 10.1007/ s00415-008-0909-4.

6. Thiel S, Langer-Gould A, Rockhoff M et al. Interferon-beta exposure during first trimester is safe in women with multiple sclerosis – a prospective cohort study from the German multiple sclerosis and pregnancy registry. Mult Scler 2016; 22(6): 801–809. doi: 10.1177/ 1352458516634872.

7. Sandberg-Wollheim M, Alteri E, Moraga MS et al. Pregnancy outcomes in multiple sclerosis following subcutaneous interferon beta-1a therapy. Mult Scler 2011; 17(4): 423–430. doi: 10.1177/ 1352458510394610.

8. Langer-Gould AM. The pill times 2: what every woman with multiple sclerosis should know. Neurology 2014; 82(8): 654–655. doi: 10.1212/ WNL.0000000000000155.

9. Kieseier BC, Benamor M. Pregnancy outcomes folowing maternal and paternal exposure to teriflunomid during treatment for relapsing-remitting multiple sclerosis. Neurol Ther 2014; 3(2): 133–138. doi: 10.1007/ s40120-014-0020-y.

10. EMA. Tecfidera (dimethyl fumarate): EPAR – product information. [online]. Available from URL: https:/ / www.ema.europa.eu/ documents/ other/ tecfidera-product-information-approved-chmp-5-november-2015-pending-endorsement-european-commission_en.pdf.

11. Gold R, Phillips JT, Havrdova E et al. Delayed-release dimethyl fumarate and pregnancy: preclinical studies and pregnancy outcomes from clinical trials and postmarketing experience. Neurol Ther 2015; 4(2): 93–104. doi: 10.1007/ s40120-015-0033-1.

12. Li J, Fox R, Phillip S et al. Delayed-release dimethyl fumarate and pregnancy: preclinical studies and pregnancy outcomes from clinical trials and postmarketing experience (P608). 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis 2015, Barcelona, Spain.

13. Everage NJ, Liu S, Yun J et al. Pregnancy outcomes with delayed-release dimethyl fumarate: interim results from an internatiol registry (EP1736). 7th Joint ECTRIMS-ACTRIMS meeting 2017, Paris, France.

14. Biogen. Periodic Safety Update Report 2017. EMA Tysabri PML update 2018

15. EMA. Gilenya (fingolimod): EPAR – product information. [online]. Available from URL: https:/ / www.ema.europa.eu/ documents/ product-information/ gilenya-epar-product-information_en.pdf.

16. EMA. Mavenclad (cladribin): EPAR – product information. [online]. Available from URL: https:/ / www.ema.europa.eu/ documents/ product-information/ mavenclad-epar-product-information_en.pdf.

17. Hellwig K, Haghikia A, Gold R. Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment. Mult Scler 2011; 17(8): 958–963. doi: 10.1177/ 1352458511401944.

18. Ebrahimi N, Herbstritt S, Gold R et al. Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study. Mult Scler 2015; 21(2): 198–205. doi: 10.1177/ 1352458514546790.

19. Portaccio E. Pregnancy outcomes and disease activity after exposure to natalizumab in patients with multiple sclerosis. ECTRIMS Online Lib 2014; 11: 64544.

20. Ciron J, Hautecoeur P, Mathis S et al. Natalizumab throughout pregnancy: risk of low platelet count in the newborn at delivery. Rev Neurol (Paris) 2016; 172(2): 165–166. doi: 10.1016/ j.neurol.2015.07.007.

21. Haghikia A, Langer-Gould A, Rellensmann G et al. Natalizumab use during the third trimester of pregnancy. JAMA Neurol 2014; 71(7): 891–895. doi: 10.1001/ jamaneurol.2014.209.

22. Lemtrada (alemtuzumab): EPAR – product information. [online]. Available from URL: https:/ / www.ema.europa.eu/ documents/ overview/ lemtrada-epar-summary-public_en.pdf.

23. Chakravarty EF, Murray ER, Kelman A et al. Pregnancy outcomes after maternal exposure to rituximab. Blood 2011; 117(5): 1499–1506. doi: 10.1182/ blood-2010-07-295444.

24. Vaidyanathan A, McKeever K, Anand B et al. Developmental immunotoxicology assessment of rituximab in cynomolgus monkeys. Toxicol Sci 2011; 119(1): 116–125. doi: 10.1093/ toxsci/ kfq316.

25. EMA. Ocrevus (ocrelizumab): EPAR – product information. [online]. Available from URL: https:/ / www.ema.europa.eu/ documents/ product-information/ ocrevus-epar-product-information_en.pdf.

26. Stewart DJ, Green RM, Mikhael NZ et al. Human autopsy tissue concentrations of mitoxantrone. Cancer Treat Rep 1986; 70(11): 1255–1261.

27. Almas S, Vance J, Baker T et al. Management of multiple sclerosis in the breastfeeding mother. Mult Scler Int 2016; 2016: 6527458. doi: 10.1155/ 2016/ 6527458.

28. Sellebjerg F, Barnes D, Filippini G et al. EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses. Eur J Neurol 2005; 12(12): 939–946. doi: 10.1111/ j.1468-1331.2005.01352.x.

29. Ferrero S, Esposito F, Pretta S et al. Fetal risks related to the treatment of multiple sclerosis during pregnancy and breastfeeding. Expert Rev Neurother 2006; 6(12): 1823–1831. doi: 10.1586/ 14737175.6.12.1823.

30. Enns GM, Roeder E, Chan RT et al. Apparent cyclophosphamide (cytoxan) embryopathy: a distinct phenotype? Am J Med Genet 1999; 86(3): 237–241.

31. Fukutani K, Ishida H, Shinohara M et al. Suppression of spermatogenesis in patients with Behçet’s disease treated with cyclophosphamide and colchicine. Fertil Steril 1981; 36(1): 76–80.

32. Radomski JS, Ahlswede BA, Jarrell BE et al. Outcomes of 500 pregnancies in 335 female kidney, liver, and heart transplant recipients. Transplant Proc 1995; 27(1): 1089–1090.

33. Paavilainen T, Kurki T, Parkkola R et el. Magnetic resonance imaging of the brain used to detect early post-partum activation of multiple sclerosis. Eur J Neurol 2007; 14(11): 1216–1221. doi: 10.1111/ j.1468-1331.2007.01927.x.

34. Hellwig K, Rockhoff M, Herbstritt S et al. Exclusive breastfeeding and the effect on postpartum multiple sclerosis relapses. JAMA Neurol 2015; 72(10): 1132–1138. doi: 10.1001/ jamaneurol.2015.1806.

35. Langer-Gould A, Huang SM, Gupta R et al. Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis. Arch Neurol 2009; 66(8): 958–963. doi: 10.1001/ archneurol.2009.132.

36. Hellwig K, Kuge M, Gold R. Exclusive breastfeeding reduces the risk of postpartum relapses – a prospective study from the German MS and pregnancy registry. [abstract]. Neurology 2011; 76 (Suppl 4): A273.

37. Portaccio E, Ghezzi A, Hakiki B et al. Breastfeeding is not related to postpartum relapses in multiple sclerosis. Neurology 2011; 77: 145–150. doi: 10.1212/ WNL.0b013e318224afc9.

38. Vukusic S, Confavreux C. One can prevent post-partum MS relapses by exclusive breast feeding: no. Mult Scler 2013; 19(12): 1565–1566. doi: 10.1177/ 135 2458513503054.

39. Pakpoor J, Disanto G, Lacey MV et al. Breastfeeding and multiple sclerosis relapses: a meta-analysis. J Neurol 2012; 259(10): 2246–2248. doi: 10.1007/ s00415-012-6553-z.

40. Coyle PK. Management of women with multiple sclerosis through pregnancy and after childbirth. Ther Adv Neurol Disord 2016; 9(3): 198–210. doi: 10.1177/ 1756285616631897.

41. Almas S, Vance J, Baker T et al. Management of multiple sclerosis in the breastfeeding mother. Mult Scler Int 2016; 2016: 6527458. doi: 10.1155/ 2016/ 6527458.

42. Hale TW, Siddiqui AA, Baker TE. Transffer on interferon beta-1a into human breastmilk. Breastfeed Med 2012; 7(2): 123–125. doi: 10.1089/ bfm.2011.0044.

43. Boz C, Terzi M, Zengin Karahan S et al. Safety of IV pulse methylprednisolone therapy during breastfeeding in patients with multiple sclerosis. Mult Scler 2017; 24(9): 1205–1211. doi: 10.1177/ 1352458517717806.