Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5 years of post-marketing experience

Abstract

Background:

Teriflunomide is contraindicated in pregnancy. Some pregnancies have occurred despite guidance to use effective contraception.

Objectives:

To report outcomes of pregnancies occurring in teriflunomide clinical trials and the post-marketing setting.

Methods:

Outcomes are summarized for pregnancies in teriflunomide monotherapy clinical trials and the post-marketing setting (data cutoff: December 2017).

Results:

Of 437 confirmed teriflunomide-exposed pregnancies, 222 had known outcomes (70 from clinical trials; 152 from the post-marketing setting); 161 were reported prospectively and 61 retrospectively. There were 107 (48.2%) live births, 63 (28.4%) elective abortions, 47 (21.2%) spontaneous abortions, 3 (1.4%) ectopic pregnancies, 1 (0.5%) stillbirth, and 1 (0.5%) maternal death leading to fetal death. Four birth defects were reported among cases with known pregnancy outcome: ureteropyeloectasia (only defect considered major); congenital hydrocephalus; ventricular septal defect; and malformation of right foot valgus. A case of cystic hygroma was identified on antenatal ultrasound (pregnancy outcome unknown). One elective abortion followed prenatal diagnosis of fetal anomaly (blighted ovum). The risk of major birth defects in prospectively reported live birth/stillbirth outcomes was 3.6% (1/28) in clinical trials and 0.0% (0/51) in post-marketing reports.

Conclusions:

Outcomes were consistent with the general population. Current human data do not indicate a teratogenic signal in teriflunomide-exposed pregnancies.

Keywords

Multiple sclerosis pregnancy safety teriflunomide clinical study post-marketing

Get full access to this article

View all access options for this article.

References

AUBAGIO prescribing information . Cambridge: Genzyme Corporation, a Sanofi company, http://products.sanofi.us/aubagio/aubagio.pdf (2012, accessed 4 April 2018).

AUBAGIO (teriflunomide) summary of product characteristics . European Medicines Agency, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002514/WC500148682.pdf (2017, accessed 4 April 2018).

Freedman

MS.

Teriflunomide in relapsing multiple sclerosis: therapeutic utility. Ther Adv Chronic Dis 2013; 4(5): 192–205.

Kieseier

Benamor

Pregnancy outcomes following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis. Neurol Ther 2014; 3(2): 133–138.

O’Connor

Freedman

, et al. A phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 2006; 66(6): 894–900.

Confavreux

Freedman

, et al. Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years. Mult Scler 2012; 18(9): 1278–1289.

O’Connor

Wolinsky

Confavreux

, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 2011; 365(14): 1293–1303.

O’Connor

Comi

Freedman

, et al. Long-term safety and efficacy of teriflunomide: nine-year follow-up of the randomized TEMSO study. Neurology 2016; 86(10): 920–930.

Confavreux

O’Connor

Comi

, et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 2014; 13(3): 247–256.

10.

Miller

Wolinsky

Kappos

, et al. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 2014; 13(10): 977–986.

11.

Vermersch

Czlonkowska

Grimaldi

, et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler 2014; 20(6): 705–716.

12.

Coyle

Khatri

Edwards

, et al. Patient-reported outcomes in relapsing forms of MS: real-world, global treatment experience with teriflunomide from the Teri-PRO study. Mult Scler Relat Disord 2017; 17: 107–115.

13.

Freedman

Wolinsky

Truffinet

, et al. A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. Mult Scler J Exp Transl Clin 2015; 1: 2055217315618687.

14.

Freedman

Wolinsky

Wamil

, et al. Teriflunomide added to interferon-β in relapsing multiple sclerosis. Neurology 2012; 78: 1877–1885.

15.

Lebrun-Frenay

Rog

Benamor

, et al. Teriflunomide (Aubagio^®) international pregnancy registry: enrollment update. Neurology 2018; 90(15, Suppl.): P4.371.

16.

FDA Draft Guidance. Pregnancy, lactation, and reproductive potential: labeling for human prescription drug and biological products—content and format. Guidance for industry. Silver Spring, MD: Center for Biologics Evaluation and Research (CBER), Center for Drug Evaluation and Research (CDER), Food and Drug Administration, U.S. Department of Health and Human Services, 2014, pp. 1–24.

17.

Davenport

Edling

Finn

, et al. Teriflunomide mechanism of action: linking species’ sensitivities to pregnancy outcomes. Neurology 2016; 86(16 Suppl.): P2.068.

18.

Miller

Fineman

Smith

DW.

Postaxial acrofacial dysostosis syndrome. J Pediatr 1979; 95(6): 970–975.

19.

Buckingham

Lee

, et al. Exome sequencing identifies the cause of a Mendelian disorder. Nat Genet 2010; 42(1): 30–35.

20.

Nybo Andersen

Wohlfahrt

Christens

, et al. Maternal age and fetal loss: population based register linkage study. BMJ 2000; 320(7251): 1708–1712.

21.

Chambers

Johnson

Robinson

, et al. Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum 2010; 62(5): 1494–1503.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.01 MB