Disease modifying treatment and pregnancy Review article
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Published:
Sep 30, 2020
Keywords:
disease modifying treatment, pregnancy, safety
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Abstract
Knowledge about the safety of immunomodulatory therapy of MS and its impact on the pregnancy is very important. Drugs of the first-line and second-line therapy have different safety profiles and with available new data our view of specific therapies is constantly changing. Knowledge of this issue allow us to plan correctly the therapy of patients of reproductive age, who are planning a pregnancy as well as to avoid potential consequences of an unplanned pregnancy.
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References
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2. Houtchens M, Edwards N, Schneider G et al. Pregnancy rates and outcomes in women with and without MS in the United States. Neurology. 2018; 91(17): e1559-69.
3. Confavreux Ch, Hutchinson H, Hours M et al. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med. 1998; 339(5): 285-91.
4. Langer-Gould A. Prezentacja: ANN Annual Meeting, 2019. Platform Session S6.007.
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6. Hughes S, Spelman T, Gray O et al. Predictors and dynamics of postpartum relapses in women with multiple sclerosis. Mult Scler. 2014; 20(6): 739-46.
7. Rebif®. ChPL, Avonex®. ChPL. Betaferon®, ChPL, Plegridy®. ChPL.
8. Ferrero S, Pretta S, Ragni N. Multiple sclerosis: Management issues during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2004; 115: 3-9.
9. Boskovic R, Wide R, Wolpin J et al. The reproductive effects of beta interferon therapy in pregnancy: A longitudinal cohort. Neurology. 2005; 65: 807-11.
10. Sandberg-Wollheim M, Frank D, Goodwin TM et al. Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis. Neurology. 2005; 65: 802-6.
11. Coyle PK, Roberts S, Scheuerle A et al. The Betaseron (Interferon Beta-1b) Pregnancy Registry. Int J MS Care. 2010; 12: 26-8.
12. Foulds P, Richman S, Glick G et al. Pregnancy outcomes from the Avonex® (interferon beta-1a) pregnancy exposure registry. Mult Scler. 2010; 16: 894-6.
13. Hellwig K, Geissbuehler Y, Sabidó M et al. Pregnancy outcomes in interferon-beta-exposed patients with multiple sclerosis: results from the European Interferon-beta Pregnancy Registry. J Neurol. 2020; 267: 1715-23.
14. Burkill S, Vattulainen P, Geissbuehler Y et al. The association between exposure to interferon-beta during pregnancy and birth measurement in offspring of women with multiple sclerosis. PLoS One. 2019; 14(12): e0227120.
15. Hellwig K. The fetal/child perspective – risks related drug exposure of the child, breastfeeding and when to reassume medication. ECTRIMS. 2019 Online Library.
16. Hale TW, Siddiqui AA, Baker TE. Transfer of interferon b-1a into human breastmilk. Breastfeed Med. 2012; 7: 123-5.
17. Cilpea A, Langer-Gould A, Stahl A et al. Safety of potential breast milk exposure to INF-β or glatiramer acetate. One-year infant outcomes. Neurology. 2020; 7(4): e757.
18. Montalban X, Gold R, Thompson A et al. ECTRIMS/EAN guadline on the pharmacological treatment of people with multiple sclerosis. Eur J Neurol. 2018; 25: 215-37.
19. Dobson R, Dassan P, Roberts M et al. UK consensus on pregnancy in multiple sclerosis: Association of British Neurologists’ guidelines. Pract Neurol. 2019; 19: 106-14.
20. Ministerstwo Zdrowia. Obwieszczenie Ministra Zdrowia z dnia 24 sierpnia 2020 r. w sprawie wykazu refundowanych leków, środków spożywczych specjalnego przeznaczenia żywieniowego oraz wyrobów medycznych na 1 września 2020 r.
21. Copaxone®. ChPL
22. Coyle P, Johnson K, Pardo L. Pregnancy outcomes in patients with multiple sclerosis treated with glatiramer acetate (Copaxone). Neurology. 2003; 60: 60-2.
23. Fragoso YD, Finkelsztejn A, Kaimen-Maciel DR et al. Long term use of glatiramer acetate by 11 pregnant women with multiple sclerosis; a retrospective, multicentre case series. CNC Drugs. 2010; 24: 969-76.
24. Salminen HJ, Leggett H, Boggild M. Glatiramer acetate exposure in pregnancy: preliminary safety and birth outcomes. J Neurol. 2010; 257: 2020-3.
25. Giannini M, Portaccio E, Ghezzi A et al. Pregnancy and fetal outcomes after glatiramer acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study. BMC Neurol. 2012; 12: 124-6.
26. Neudorfer O, Baruch P, Kolodny S et al. Pregnancy Outcomes in patients with MS expose to branded glatiramer acetate. Prezentacja: AAN. 2017; P1365.
27. Hellwig K, Neudorfer O, Melamed-Gal S et al. Pregnancy outcomes in patients with multiple sclerosis and exposure branded glatiramer acetate during all three trimesters. Prezentacja: ECTRIMS. 2017; P765.
28. Queiber-Wahrendorf A, Neumann D, Adamus E. Early childhood development up to kindergarten age after glatiramer acetate exposure during early pregnancy in women with multiple sclerosis. Prezentacja: AAN. 2017; P1348.
29. Hellwig K, Gold R. Glatiramer acetate and interferon-beta throughout gestation and postpartum in women with multiple sclerosis. J Neurol. 2011; 258: 502-3.
30. Tecfidera®. ChPL .
31. Gold RJ, 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: 93-104.
32. Li J, Fox R, Phillips J et al. Delayed-release dimethyl fumarate and pregnancy: Preclinical studies and pregnancy outcomes from clinical trials and post-marketing experience. Prezentacja: ECTRIMS. 2015; P608.
33. Hellwig K, Rog D, McGuigan Ch et al. Interim analysis of pregnancy outcomes following exposure to dimethyl fumarate in a prospective international registry. ECTRIMS-ACTRIMS. 2020; P0345.
34. Aubagio®. ChPL.
35. Kieseier B, Benamor M. Pregnancy outcome following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis. Neurol Ther. 2014; 3: 133-8.
36. Vukusic S, Coyle P, Jurgensen S et al. Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5-years of post-marketing experience. Mult Scler. 2020; 26(7): 829-36.
37. Aubagio®. ChPL.
38. Gilenya®. ChPL .
39. Collins W, Francis G, Koren G et al. Lack of interaction between fingolimod (FTY720) and oral contraceptives, and pregnancy experience in clinical program of fingolimod in MS. AAN. 2011; P7184.
40. Geissbuhler Y, Butzkueven H, Harnandez-Diaz S et al. Multinational Gilenya Pregnancy Exposure Registry: preliminary results. Prezentacja: AAN. 2013; P403.
41. Geissbuhler Y, Koren G, Wang H et al. Pregnancy outcomes after exposure to fingolimod and in the general population. Prezentacja: ECTRIMS. 2015; P61.
42. Lopez-Leon S. Effect of fingolimod on pregnancy outcomes in patients with multiple sclerosis. Prezentacja: ECTRIMS. 2019; P411.
43. EMA. Updated restrictions for Gilenya: multiple sclerosis medicine not to be used in pregnancy .
44. Prach LM, Moore A, Rezzallah B et al. Cumulative update on pregnancy outcomes afer fingolimod treatment in patients with multiple sclerosis. ECTRIMS-ACTRIMS. 2020; P1118.
45. Mavenclad®. ChPL .
46. Giovannoni G, Galazka A, Schick R et al. Pregnancy outcomes during the clinical development program of cladribine in multiple sclerosis: An integrated analysis of safety. Drug Saf. 2020; 43(7): 635-43.
47. Tysabri®. ChPL .
48. 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.
49. Portaccio E, Annovazzi P, Ghezzi A et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology. 2018; 90(10): e823-e831.
50. Peng A, Qiu X, Zhang L et al. Natalizumab exposure during pregnancy in multiple sclerosis: a systematic review. J Neurol Science. 2019; 396: 202-5.
51. Haghikia A, Langer-Gould A, Rellensmann G et al. Natalizumab use during the third trimester of pregnancy. JAMA Neurol. 2014; 71(7): 891-5.
52. Friend S, Richman S, Bloomgren G et al. Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016; 16(1): 150. https://doi.org/10.1186/s12883-016-0674-4.
53. Kümpfel T, Thiel S, Meinl I et al. Long-term exposure to natalizumab during pregnancy - a prospective case series from the German Multiple Sclerosis and Pregnancy Registry. Prezentacja: ECTRIMS. 2017.
54. Portaccio E, Moiola L, Martinelli V et al. Pregnancy decison-making in women withmultiple sclerosis treated with natalizumab: II maternal risks. Neurology. 2018; 90: 832-9.
55. Baker T, Cooper S, Kessler L et al. Transfer of natalizumab into breast milk in a mother with multiple sclerosis. J Hum Lact. 2015; 31(2): 233-6.
56. Ocrevus®. ChPL .
57. Bove R, Oreja-Guevera C, Hellwig K et al. Pregnancy outcomes in patients treated with ocrelizumab. ACTRIMS-ECTRIMS. 2020; P1132.
58. Chakravarty E, Murray E, Kelman A et al. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011; 117: 1499-506.
59. Lemtrada®. ChPL .
60. Rog D. Pregnancy outcomes in patients with RRMS Treated With Alemtuzumab From the Clinical Development Program. Prezentacja: ECTRIMS. 2017; P749.
61. McCarthy C, Brown J, Tuohy O et al. Long-term safety of alemtuzumab in relapsing-remitting multiple sclerosis: pregnancy and infection data from a cohort of patients on open label studies in Cambridge, UK. Long-term safety of alemtuzumab in relapsing-remitting multiple sclerosis: pregnancy and infection data from a cohort of patients on open label studies in Cambridge. Prezentacja: ECTRIMS. 2015.
62. Gerbershagen KS, Thiel S, Limmroth V et al. Disease activity during pregnancy and pregnancy outcomes in patients with multiple sclerosis (MS) treated with alemtuzumab – A case series from the German MS and pregnancy registry. Prezentacja: ECTRIMS. 2016; P862.
63. Daniels G, Vladic A, Brinar V et al. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. J Clin Endocrinol Metab. 2014; 99: 80-9.
64. Rog D. Pregnancy outcomes in patients with RRMS treated with alemtuzumab from the clinical development program. Prezentacja: ECTRIMS. 2017; P749.
65. Celius E, Ciplea A, Drulović J et al. Alemtuzumab and pregnancy – case series from the German MS and Pregnancy Registry, Norway and Serbia. Prezentacja: ECTRIMS. 2018; P915.
2. Houtchens M, Edwards N, Schneider G et al. Pregnancy rates and outcomes in women with and without MS in the United States. Neurology. 2018; 91(17): e1559-69.
3. Confavreux Ch, Hutchinson H, Hours M et al. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med. 1998; 339(5): 285-91.
4. Langer-Gould A. Prezentacja: ANN Annual Meeting, 2019. Platform Session S6.007.
5. Fragoso Y, Adoni T, Vasconcelos C. Practical evidence-based recommendations for patients with multiple sclerosis who want to have children. Neurol Ther. 2018; 7(2): 207-32.
6. Hughes S, Spelman T, Gray O et al. Predictors and dynamics of postpartum relapses in women with multiple sclerosis. Mult Scler. 2014; 20(6): 739-46.
7. Rebif®. ChPL, Avonex®. ChPL. Betaferon®, ChPL, Plegridy®. ChPL.
8. Ferrero S, Pretta S, Ragni N. Multiple sclerosis: Management issues during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2004; 115: 3-9.
9. Boskovic R, Wide R, Wolpin J et al. The reproductive effects of beta interferon therapy in pregnancy: A longitudinal cohort. Neurology. 2005; 65: 807-11.
10. Sandberg-Wollheim M, Frank D, Goodwin TM et al. Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis. Neurology. 2005; 65: 802-6.
11. Coyle PK, Roberts S, Scheuerle A et al. The Betaseron (Interferon Beta-1b) Pregnancy Registry. Int J MS Care. 2010; 12: 26-8.
12. Foulds P, Richman S, Glick G et al. Pregnancy outcomes from the Avonex® (interferon beta-1a) pregnancy exposure registry. Mult Scler. 2010; 16: 894-6.
13. Hellwig K, Geissbuehler Y, Sabidó M et al. Pregnancy outcomes in interferon-beta-exposed patients with multiple sclerosis: results from the European Interferon-beta Pregnancy Registry. J Neurol. 2020; 267: 1715-23.
14. Burkill S, Vattulainen P, Geissbuehler Y et al. The association between exposure to interferon-beta during pregnancy and birth measurement in offspring of women with multiple sclerosis. PLoS One. 2019; 14(12): e0227120.
15. Hellwig K. The fetal/child perspective – risks related drug exposure of the child, breastfeeding and when to reassume medication. ECTRIMS. 2019 Online Library.
16. Hale TW, Siddiqui AA, Baker TE. Transfer of interferon b-1a into human breastmilk. Breastfeed Med. 2012; 7: 123-5.
17. Cilpea A, Langer-Gould A, Stahl A et al. Safety of potential breast milk exposure to INF-β or glatiramer acetate. One-year infant outcomes. Neurology. 2020; 7(4): e757.
18. Montalban X, Gold R, Thompson A et al. ECTRIMS/EAN guadline on the pharmacological treatment of people with multiple sclerosis. Eur J Neurol. 2018; 25: 215-37.
19. Dobson R, Dassan P, Roberts M et al. UK consensus on pregnancy in multiple sclerosis: Association of British Neurologists’ guidelines. Pract Neurol. 2019; 19: 106-14.
20. Ministerstwo Zdrowia. Obwieszczenie Ministra Zdrowia z dnia 24 sierpnia 2020 r. w sprawie wykazu refundowanych leków, środków spożywczych specjalnego przeznaczenia żywieniowego oraz wyrobów medycznych na 1 września 2020 r.
21. Copaxone®. ChPL
22. Coyle P, Johnson K, Pardo L. Pregnancy outcomes in patients with multiple sclerosis treated with glatiramer acetate (Copaxone). Neurology. 2003; 60: 60-2.
23. Fragoso YD, Finkelsztejn A, Kaimen-Maciel DR et al. Long term use of glatiramer acetate by 11 pregnant women with multiple sclerosis; a retrospective, multicentre case series. CNC Drugs. 2010; 24: 969-76.
24. Salminen HJ, Leggett H, Boggild M. Glatiramer acetate exposure in pregnancy: preliminary safety and birth outcomes. J Neurol. 2010; 257: 2020-3.
25. Giannini M, Portaccio E, Ghezzi A et al. Pregnancy and fetal outcomes after glatiramer acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study. BMC Neurol. 2012; 12: 124-6.
26. Neudorfer O, Baruch P, Kolodny S et al. Pregnancy Outcomes in patients with MS expose to branded glatiramer acetate. Prezentacja: AAN. 2017; P1365.
27. Hellwig K, Neudorfer O, Melamed-Gal S et al. Pregnancy outcomes in patients with multiple sclerosis and exposure branded glatiramer acetate during all three trimesters. Prezentacja: ECTRIMS. 2017; P765.
28. Queiber-Wahrendorf A, Neumann D, Adamus E. Early childhood development up to kindergarten age after glatiramer acetate exposure during early pregnancy in women with multiple sclerosis. Prezentacja: AAN. 2017; P1348.
29. Hellwig K, Gold R. Glatiramer acetate and interferon-beta throughout gestation and postpartum in women with multiple sclerosis. J Neurol. 2011; 258: 502-3.
30. Tecfidera®. ChPL .
31. Gold RJ, 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: 93-104.
32. Li J, Fox R, Phillips J et al. Delayed-release dimethyl fumarate and pregnancy: Preclinical studies and pregnancy outcomes from clinical trials and post-marketing experience. Prezentacja: ECTRIMS. 2015; P608.
33. Hellwig K, Rog D, McGuigan Ch et al. Interim analysis of pregnancy outcomes following exposure to dimethyl fumarate in a prospective international registry. ECTRIMS-ACTRIMS. 2020; P0345.
34. Aubagio®. ChPL.
35. Kieseier B, Benamor M. Pregnancy outcome following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis. Neurol Ther. 2014; 3: 133-8.
36. Vukusic S, Coyle P, Jurgensen S et al. Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5-years of post-marketing experience. Mult Scler. 2020; 26(7): 829-36.
37. Aubagio®. ChPL.
38. Gilenya®. ChPL .
39. Collins W, Francis G, Koren G et al. Lack of interaction between fingolimod (FTY720) and oral contraceptives, and pregnancy experience in clinical program of fingolimod in MS. AAN. 2011; P7184.
40. Geissbuhler Y, Butzkueven H, Harnandez-Diaz S et al. Multinational Gilenya Pregnancy Exposure Registry: preliminary results. Prezentacja: AAN. 2013; P403.
41. Geissbuhler Y, Koren G, Wang H et al. Pregnancy outcomes after exposure to fingolimod and in the general population. Prezentacja: ECTRIMS. 2015; P61.
42. Lopez-Leon S. Effect of fingolimod on pregnancy outcomes in patients with multiple sclerosis. Prezentacja: ECTRIMS. 2019; P411.
43. EMA. Updated restrictions for Gilenya: multiple sclerosis medicine not to be used in pregnancy .
44. Prach LM, Moore A, Rezzallah B et al. Cumulative update on pregnancy outcomes afer fingolimod treatment in patients with multiple sclerosis. ECTRIMS-ACTRIMS. 2020; P1118.
45. Mavenclad®. ChPL .
46. Giovannoni G, Galazka A, Schick R et al. Pregnancy outcomes during the clinical development program of cladribine in multiple sclerosis: An integrated analysis of safety. Drug Saf. 2020; 43(7): 635-43.
47. Tysabri®. ChPL .
48. 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.
49. Portaccio E, Annovazzi P, Ghezzi A et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology. 2018; 90(10): e823-e831.
50. Peng A, Qiu X, Zhang L et al. Natalizumab exposure during pregnancy in multiple sclerosis: a systematic review. J Neurol Science. 2019; 396: 202-5.
51. Haghikia A, Langer-Gould A, Rellensmann G et al. Natalizumab use during the third trimester of pregnancy. JAMA Neurol. 2014; 71(7): 891-5.
52. Friend S, Richman S, Bloomgren G et al. Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016; 16(1): 150. https://doi.org/10.1186/s12883-016-0674-4.
53. Kümpfel T, Thiel S, Meinl I et al. Long-term exposure to natalizumab during pregnancy - a prospective case series from the German Multiple Sclerosis and Pregnancy Registry. Prezentacja: ECTRIMS. 2017.
54. Portaccio E, Moiola L, Martinelli V et al. Pregnancy decison-making in women withmultiple sclerosis treated with natalizumab: II maternal risks. Neurology. 2018; 90: 832-9.
55. Baker T, Cooper S, Kessler L et al. Transfer of natalizumab into breast milk in a mother with multiple sclerosis. J Hum Lact. 2015; 31(2): 233-6.
56. Ocrevus®. ChPL .
57. Bove R, Oreja-Guevera C, Hellwig K et al. Pregnancy outcomes in patients treated with ocrelizumab. ACTRIMS-ECTRIMS. 2020; P1132.
58. Chakravarty E, Murray E, Kelman A et al. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011; 117: 1499-506.
59. Lemtrada®. ChPL .
60. Rog D. Pregnancy outcomes in patients with RRMS Treated With Alemtuzumab From the Clinical Development Program. Prezentacja: ECTRIMS. 2017; P749.
61. McCarthy C, Brown J, Tuohy O et al. Long-term safety of alemtuzumab in relapsing-remitting multiple sclerosis: pregnancy and infection data from a cohort of patients on open label studies in Cambridge, UK. Long-term safety of alemtuzumab in relapsing-remitting multiple sclerosis: pregnancy and infection data from a cohort of patients on open label studies in Cambridge. Prezentacja: ECTRIMS. 2015.
62. Gerbershagen KS, Thiel S, Limmroth V et al. Disease activity during pregnancy and pregnancy outcomes in patients with multiple sclerosis (MS) treated with alemtuzumab – A case series from the German MS and pregnancy registry. Prezentacja: ECTRIMS. 2016; P862.
63. Daniels G, Vladic A, Brinar V et al. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. J Clin Endocrinol Metab. 2014; 99: 80-9.
64. Rog D. Pregnancy outcomes in patients with RRMS treated with alemtuzumab from the clinical development program. Prezentacja: ECTRIMS. 2017; P749.
65. Celius E, Ciplea A, Drulović J et al. Alemtuzumab and pregnancy – case series from the German MS and Pregnancy Registry, Norway and Serbia. Prezentacja: ECTRIMS. 2018; P915.