Evaluation of Pregnancy Outcomes in Patients with Multiple Sclerosis After Fingolimod Exposure

Overview

Journal Ther Adv Neurol Disord

Specialty Neurology

Date 2018 Dec 14

PMID 30542374

Citations 14

Authors

Yvonne Geissbuhler

Jere Vile

Gideon Koren

Morgane Guennec

Helmut Butzkueven

Hugh Tilson

Thomas M MacDonald

Kerstin Hellwig

Affiliations

Soon will be listed here.

Abstract

Background And Methods: Limited data are available on the safety of fingolimod in pregnant women. We estimated the risk of adverse pregnancy outcomes in women with multiple sclerosis (MS) exposed to fingolimod either shortly before or during pregnancy in prospectively collected cases from clinical trials, observational studies, surveillance programs, and spontaneous reports.

Results: The prevalence of major malformations among live births does not appear to be significantly higher than those in the general population and the unexposed MS population. Similarly, the prevalence of cardiac malformations observed in this analysis was not significantly different from that of the general population. Proportions of miscarriage were in line with those of the general and unexposed MS population and no specific pattern of birth defects was identified.

Conclusions: These data can help inform healthcare professionals and women with MS exposed to fingolimod during conception.

Citing Articles

Impact of disease-modifying therapies on pregnancy outcomes in multiple sclerosis: a prospective cohort study from the German multiple sclerosis and pregnancy registry.

Bast N, Dost-Kovalsky K, Haben S, Friedmann N, Witt L, Oganowski T Lancet Reg Health Eur. 2025; 48():101137.

PMID: 39811788 PMC: 11732200. DOI: 10.1016/j.lanepe.2024.101137.

Cost effectiveness of different treatment strategies with natalizumab for pregnant women with multiple sclerosis.

Walbaum M, Madhukar A, Dobson R, Cyhlarova E, Castro-Aldrete L, Chadha A J Neurol. 2025; 272(1):93.

PMID: 39776288 PMC: 11706867. DOI: 10.1007/s00415-024-12736-z.

Fingolimod, a sphingosine-1-phosphate receptor modulator, prevents neonatal bronchopulmonary dysplasia and subsequent airway remodeling in a murine model.

Sudhadevi T, Annadi A, Basa P, Jafri A, Natarajan V, Harijith A J Appl Physiol (1985). 2024; 137(5):1231-1242.

PMID: 39262336 PMC: 11563639. DOI: 10.1152/japplphysiol.00311.2024.

Validation of a Novel Method to Assess the Clinical Quality of Information in Pregnancy-Related Pharmacovigilance Case Reports: A ConcePTION Project.

van Rijt-Weetink Y, Egberts T, van Hunsel F, Lewis D, Yates L, Winterfeld U Drug Saf. 2024; 47(3):261-270.

PMID: 38183608 PMC: 10874330. DOI: 10.1007/s40264-023-01389-y.

Core Data Elements for Pregnancy Pharmacovigilance Studies Using Primary Source Data Collection Methods: Recommendations from the IMI ConcePTION Project.

Richardson J, Moore A, Bromley R, Stellfeld M, Geissbuhler Y, Bluett-Duncan M Drug Saf. 2023; 46(5):479-491.

PMID: 36976447 PMC: 10164024. DOI: 10.1007/s40264-023-01291-7.

References

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):958-63. DOI: 10.1177/1352458511401944. View

Wang J, Norman R, Wilcox A . Incidence of spontaneous abortion among pregnancies produced by assisted reproductive technology. Hum Reprod. 2004; 19(2):272-7. DOI: 10.1093/humrep/deh078. View

Dadvand P, Rankin J, Shirley M, Rushton S, Pless-Mulloli T . Descriptive epidemiology of congenital heart disease in Northern England. Paediatr Perinat Epidemiol. 2009; 23(1):58-65. DOI: 10.1111/j.1365-3016.2008.00987.x. View

Boskovic R, Wide R, Wolpin J, Bauer D, Koren G . The reproductive effects of beta interferon therapy in pregnancy: a longitudinal cohort. Neurology. 2005; 65(6):807-11. DOI: 10.1212/01.wnl.0000180575.77021.c4. View

Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J . Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990-1998). Arch Gynecol Obstet. 2002; 266(3):163-7. DOI: 10.1007/s00404-001-0265-4. View

Buss L, Tolstrup J, Munk C, Bergholt T, Ottesen B, Gronbaek M . Spontaneous abortion: a prospective cohort study of younger women from the general population in Denmark. Validation, occurrence and risk determinants. Acta Obstet Gynecol Scand. 2006; 85(4):467-75. DOI: 10.1080/00016340500494887. View

Friend S, Richman S, Bloomgren G, Cristiano L, Wenten M . Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016; 16(1):150. PMC: 4995778. DOI: 10.1186/s12883-016-0674-4. View

Rossier M, Mivelaz Y, Addor M, Sekarski N, Meijboom E, Vial Y . Evaluation of prenatal diagnosis of congenital heart disease in a regional controlled case study. Swiss Med Wkly. 2014; 144:w14068. DOI: 10.4414/smw.2014.14068. View

Egbe A, Uppu S, Lee S, Stroustrup A, Ho D, Srivastava S . Congenital malformations in the newborn population: a population study and analysis of the effect of sex and prematurity. Pediatr Neonatol. 2014; 56(1):25-30. DOI: 10.1016/j.pedneo.2014.03.010. View

10.

Kono M, Allende M, Proia R . Sphingosine-1-phosphate regulation of mammalian development. Biochim Biophys Acta. 2008; 1781(9):435-41. PMC: 2562162. DOI: 10.1016/j.bbalip.2008.07.001. View

11.

Weber-Schoendorfer C, Schaefer C . Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study. Mult Scler. 2009; 15(9):1037-42. DOI: 10.1177/1352458509106543. View

12.

Rasmussen S, Olney R, Holmes L, Lin A, Keppler-Noreuil K, Moore C . Guidelines for case classification for the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol. 2003; 67(3):193-201. DOI: 10.1002/bdra.10012. View

13.

Parker S, Mai C, Canfield M, Rickard R, Wang Y, Meyer R . Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010; 88(12):1008-16. DOI: 10.1002/bdra.20735. View

14.

Brinkmann V . Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther. 2007; 115(1):84-105. DOI: 10.1016/j.pharmthera.2007.04.006. View

15.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K . Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study. Mult Scler. 2014; 21(2):198-205. DOI: 10.1177/1352458514546790. View

16.

Herbstritt S, Langer-Gould A, Rockhoff M, Haghikia A, Queisser-Wahrendorf A, Gold R . Glatiramer acetate during early pregnancy: A prospective cohort study. Mult Scler. 2016; 22(6):810-6. DOI: 10.1177/1352458515623366. View

17.

Thiel S, Langer-Gould A, Rockhoff M, Haghikia A, Queisser-Wahrendorf A, Gold R . 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):801-9. DOI: 10.1177/1352458516634872. View