Contributions
Abstract: 205
Type: Oral
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Teriflunomide is a once-daily oral immunomodulator approved for treatment of relapsing-remitting MS in 70 countries, with ≥71,000 patients currently being treated worldwide. Although data from the clinical programme show no signal for human teratogenicity, teriflunomide is contraindicated in pregnancy based on embryo-foetal toxicity in rats and rabbits. No teratogenic signal was reported in post-marketing (PM) surveillance of leflunomide, the parent compound of teriflunomide. Despite the requirement to use reliable contraception, a number of pregnancies have been reported in patients treated with teriflunomide.
Objective: To report the outcomes of pregnancies occurring in the teriflunomide clinical programme and in the PM setting.
Methods: Pregnancy outcomes are summarized for female patients treated with teriflunomide who reported ≥1 new pregnancy during the course of monotherapy clinical studies (CS) or in the PM setting (excluding known pregnancy registry cases). Data cutoff was May 17, 2016.
Results: There were 69 pregnancies in the clinical programme and 171 in the PM setting in females treated with teriflunomide. Among the 138 pregnancies with known outcomes, 107 (including all CS cases) were reported prospectively: live birth (n=47), elective abortion (n=39), spontaneous abortion (n=20), and ectopic pregnancy (n=1). Retrospectively reported outcomes (n=31) were live birth (n=11), elective abortion (n=9), spontaneous abortion (n=9), and stillbirth (n=2). No malformations/abnormalities were reported with elective abortions. Treatment was discontinued in all CS cases and >75% of PM cases where pregnancy was not terminated, with reported use of an accelerated elimination procedure in 77% and 59% of these patients, respectively. In prospective live/still births there were 2 documented PM cases of in utero exposure in the second trimester; other cases indicated exposure preconception or first trimester. Three structural abnormalities were reported: ureteropyeloectasia in a newborn in a CS case; congenital hydrocephalus in a full-term infant and cystic hygroma (on antenatal ultrasound) in PM cases.
Conclusions: Pregnancy outcomes were consistent with those observed in the general and MS populations. Current data do not indicate a teratogenic signal in teriflunomide-exposed pregnancies. Pharmacovigilance monitoring and pregnancy registries will provide additional information to inform women of child-bearing potential about teriflunomide in pregnancy.
Disclosure: Study supported by Sanofi Genzyme.
SV: Consultancy fees, speaker fees, research grants (non-personal) or honoraria (Biogen, Geneuro, Genzyme-Sanofi, Medday, Merck Serono, Novartis, Roche and Teva).
PKC: Consulting fees (Accordant, Acorda, Bayer, Biogen Idec, Celgene, Genentech/Roche, Genzyme/Sanofi, Novartis, Serono, Teva); research support (Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, Novartis).
SJ and MB: Employees of Sanofi Genzyme.
PT: Employee of Sanofi Genzyme, with ownership interest.
CC: Compensation for serving as Editor, Associate Editor, or member of an editorial advisory board (Birth Defects Research Part A: Clinical and Molecular Teratology); 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).
Abstract: 205
Type: Oral
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Teriflunomide is a once-daily oral immunomodulator approved for treatment of relapsing-remitting MS in 70 countries, with ≥71,000 patients currently being treated worldwide. Although data from the clinical programme show no signal for human teratogenicity, teriflunomide is contraindicated in pregnancy based on embryo-foetal toxicity in rats and rabbits. No teratogenic signal was reported in post-marketing (PM) surveillance of leflunomide, the parent compound of teriflunomide. Despite the requirement to use reliable contraception, a number of pregnancies have been reported in patients treated with teriflunomide.
Objective: To report the outcomes of pregnancies occurring in the teriflunomide clinical programme and in the PM setting.
Methods: Pregnancy outcomes are summarized for female patients treated with teriflunomide who reported ≥1 new pregnancy during the course of monotherapy clinical studies (CS) or in the PM setting (excluding known pregnancy registry cases). Data cutoff was May 17, 2016.
Results: There were 69 pregnancies in the clinical programme and 171 in the PM setting in females treated with teriflunomide. Among the 138 pregnancies with known outcomes, 107 (including all CS cases) were reported prospectively: live birth (n=47), elective abortion (n=39), spontaneous abortion (n=20), and ectopic pregnancy (n=1). Retrospectively reported outcomes (n=31) were live birth (n=11), elective abortion (n=9), spontaneous abortion (n=9), and stillbirth (n=2). No malformations/abnormalities were reported with elective abortions. Treatment was discontinued in all CS cases and >75% of PM cases where pregnancy was not terminated, with reported use of an accelerated elimination procedure in 77% and 59% of these patients, respectively. In prospective live/still births there were 2 documented PM cases of in utero exposure in the second trimester; other cases indicated exposure preconception or first trimester. Three structural abnormalities were reported: ureteropyeloectasia in a newborn in a CS case; congenital hydrocephalus in a full-term infant and cystic hygroma (on antenatal ultrasound) in PM cases.
Conclusions: Pregnancy outcomes were consistent with those observed in the general and MS populations. Current data do not indicate a teratogenic signal in teriflunomide-exposed pregnancies. Pharmacovigilance monitoring and pregnancy registries will provide additional information to inform women of child-bearing potential about teriflunomide in pregnancy.
Disclosure: Study supported by Sanofi Genzyme.
SV: Consultancy fees, speaker fees, research grants (non-personal) or honoraria (Biogen, Geneuro, Genzyme-Sanofi, Medday, Merck Serono, Novartis, Roche and Teva).
PKC: Consulting fees (Accordant, Acorda, Bayer, Biogen Idec, Celgene, Genentech/Roche, Genzyme/Sanofi, Novartis, Serono, Teva); research support (Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, Novartis).
SJ and MB: Employees of Sanofi Genzyme.
PT: Employee of Sanofi Genzyme, with ownership interest.
CC: Compensation for serving as Editor, Associate Editor, or member of an editorial advisory board (Birth Defects Research Part A: Clinical and Molecular Teratology); 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).