Pregnancy Outcomes in Patients with MS Treated with Teriflunomide: Postmarketing Data

Background: Teriflunomide is a once-daily oral immunomodulator approved for treatment of relapsing forms of MS. Data from the clinical program showed no signal for human teratogenicity in teriflunomide-exposed pregnancies. Additionally, no teratogenic signal has been reported in postmarketing (PM) surveillance of leflunomide, the parent compound of teriflunomide, which has been approved for treatment of rheumatoid arthritis since 1998. However, teriflunomide is contraindicated in pregnancy based on embryo-fetal toxicity in rats and rabbits. Despite the requirement to use reliable contraception, pregnancies have occurred in patients treated with teriflunomide.

Objectives: To report pregnancy outcomes for female patients treated with teriflunomide in the PM setting.

Methods: Pregnancy outcomes are summarized for female patients treated with teriflunomide in the PM setting from Sep 2012 to May 2016, excluding known pregnancy registry cases.

Results: Of the 169 pregnancies in the PM setting, outcomes are known for 67 cases (follow-up data not available for remaining cases). Among these 67 pregnancies, 37 were reported prospectively (prior to prenatal tests that could provide information on the fetus): live birth (n=20), elective abortion (n=8), spontaneous abortion (n=9). The remaining 30 pregnancies were reported retrospectively: live birth (n=10), elective abortion (n=9), spontaneous abortion (n=10), and 1 fetal death at 35 weeks for which the cause and details are unknown. No malformations/abnormalities were reported with elective abortions. Mean (SD) duration of teriflunomide treatment prior to pregnancy was 4.4 (6.7) months. An accelerated elimination procedure to reduce plasma concentrations of teriflunomide was used in 60% of pregnancies with live births. The final dose of teriflunomide was administered pre-conception or in the first trimester for all but 4 cases: 3 patients exposed in the second (≥14 to ≤28 weeks) and 1 patient in the third trimester (>28 weeks). Of these 169 pregnancies, 2 structural abnormalities were reported: 1 case of congenital hydrocephalus (full-term pregnancy), and 1 cystic hygroma on antenatal ultrasound (pregnancy with unknown outcome). Patient-level data from the PM setting will also be presented. 

Conclusions: Current data from pregnancies exposed to teriflunomide show no teratogenic signal and are 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