Pregnancy Outcomes in Patients With MS Treated With Teriflunomide: Clinical Study and Postmarketing Data (P4.361)

Objective: To report the outcomes of pregnancies occurring in the teriflunomide clinical studies (CS) and postmarketing (PM) settings. Background: Teriflunomide is approved for treatment of relapsing forms of MS in 80 countries, with ~162,000 patient-years of exposure since approval. The teriflunomide CS showed no signal for human teratogenicity. Additionally, no teratogenic signal has been reported in PM surveillance of the parent compound, leflunomide (approved for rheumatoid arthritis since 1998). However, teriflunomide is contraindicated in pregnancy based on embryo-fetal toxicity in rats and rabbits. Despite requirements for reliable contraception, pregnancies have occurred in teriflunomide-treated patients. Design/Methods: Pregnancy outcomes are summarized for female patients treated with teriflunomide during monotherapy CS or in PM settings (excluding pregnancy registry cases). Data cutoff was May 17, 2016. Results: Overall, 62 pregnancies were reported in CS and 169 in PM settings. Among the 129 pregnancies with known outcomes, 99 (including all CS cases) were reported prospectively: live birth (n=42), elective abortion (n=38), spontaneous abortion (n=17), and ectopic pregnancy (n=2). Retrospectively reported outcomes (n=30) were: live birth (n=10), elective abortion (n=9), spontaneous abortion (n=10), fetal death (n=1; ≥20 gestation weeks). No malformations/abnormalities were reported with elective abortions. An accelerated elimination procedure for teriflunomide was used in 82% of CS and 60% of PM cases with live births. Last dose of teriflunomide was administered at pre-conception or in the first trimester for all but 4 cases; all were PM cases, 3 exposed in the second and 1 in the third trimester. Three structural abnormalities were reported: ureteropyeloectasia in a newborn CS case (pre-term infant), congenital hydrocephalus (full-term), and cystic hygroma (on antenatal ultrasound; outcome unknown) in separate PM cases. Conclusions: Current data from teriflunomide-exposed pregnancies show no teratogenic signal, consistent with the 20-year PM experience with leflunomide. These data provide valuable information to healthcare providers and female patients of child-bearing potential. Study Supported by: Sanofi. Disclosure: Dr. Vukusic has nothing to disclose. Dr. Coyle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees (AbbVie, Accordant, Acorda, Bayer, Biogen Idec, Celgene, Genentech/Roche, Genzyme/Sanofi, Novartis, Serono, Teva). Dr. Coyle has received research support from Research support (Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, Novartis, Opexa). Dr. Jurgensen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Jurgensen has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Truffinet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Truffinet has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Benamor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Poole has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Chavin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Chambers has received personal compensation in an editorial capacity for Compensation for serving as Editor, Associate Editor, or member of an editorial advisory board (Birth Defects Research Part A: Clinical and Molecular Teratology). Dr. Chambers has received research support from Research support unrelated to this study (AAAAI/VAMPS, AbbVie Laboratories, Amgen Inc., Bristol-Myers/Squibb, Celgene, Genzyme Sanofi-Aventis, GlaxoSmithKline, Hoffman-La Roche-Genentech, Janssen Pharmaceuticals, Pfizer, Inc., Seqirus, Takeda, UCB USA).