https://doi.org/10.1177/1352458519843055 https://doi.org/10.1177/1352458519843055 MULTIPLE SCLEROSIS MSJ JOURNAL journals.sagepub.com/home/msj 1 Multiple Sclerosis Journal 1–8 DOI: 10.1177/ 1352458519843055 © The Author(s), 2019. Article reuse guidelines: sagepub.com/journals- permissions Introduction As approximately two-thirds of patients with multi- ple sclerosis (MS) are female and the diagnosis typically occurs during childbearing years, potential childbearing risks associated with MS disease-mod- ifying therapies (DMTs) are of interest. Clinical decision-making regarding DMT use in women of childbearing potential is guided by disease severity and consideration of pregnancy risks from prescrib- ing information. Drug labeling for pregnancy risks is based primarily on results of preclinical toxicity studies, as outcomes from human pregnancies exposed to DMTs are limited at drug approval since pregnant women are typically excluded from clini- cal trials. Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of MS in 80 countries. As a first-line treatment, terifluno- mide is an attractive option for young women newly diagnosed with MS, particularly since it is effective, convenient, easy to use, and well-tolerated. However, Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5 years of post-marketing experience Sandra Vukusic , Patricia K Coyle, Stephanie Jurgensen, Philippe Truffinet, Myriam Benamor, Salman Afsar, Annie Purvis, Elizabeth M Poole and Christina Chambers 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 clini- cal 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 Date received: 7 December 2018; revised: 25 February 2019; accepted: 16 March 2019 Correspondence to: Sandra Vukusic Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Centre Hospitalo-Universitaire de Lyon (Hospices Civils de Lyon), 59 Boulevard Pinel, 69677 Bron cedex, France. sandra.vukusic@chu-lyon. fr Sandra Vukusic Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Centre Hospitalo-Universitaire de Lyon (Hospices Civils de Lyon), Bron, France/ Observatoire Français de la Sclérose en Plaques, Centre des Neurosciences de Lyon, INSERM 1028 et CNRS UMR5292, Lyon, France/ Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France Patricia K Coyle Comprehensive Care Center, School of Medicine, Stony Brook University, Stony Brook, NY, USA Stephanie Jurgensen Salman Afsar Annie Purvis Elizabeth M Poole Sanofi, Cambridge, MA, USA Philippe Truffinet Myriam Benamor Sanofi, Chilly-Mazarin, France Christina Chambers Department of Pediatrics, Rady Children’s Hospital and University of California San Diego, La Jolla, CA, USA 843055MSJ 0 0 10.1177/1352458519843055Multiple Sclerosis JournalS Vukusic, PK Coyle research-article 2019 Original Research Paper