MS and genderThursday, October 03, 2013, 15:31 - 15:43
Cumulative data on pregnancy outcomes after exposure to fingolimod K. Hellwig, G. Koren, H. Butzkueven, H. Tilson, S. Hernández-Diaz, T. Macdonald, E. Kornyeyeva, E. Plana, Y. Lu, M. Cremer, R.K Amar, R. Schlosshauer, W. Collins, Y. Geissbühler, G. Karlsson (Bochum, DE; Toronto, CA; Parkville, AU; Chapel Hill, Boston, US; Dundee, GB; East Hanover, US; Barcelona, ES; Basel, CH)
Background: Fingolimod 0.5 mg once daily an oral, sphingosine 1-phosphate receptor modulator approved for treatment of relapsing multiple sclerosis, has a well characterized safety profile based on a large clinical trial program and post-marketing experience. Because of potential risk of foetal toxicity based on animal studies, women of childbearing age are recommended to use effective contraception during treatment with fingolimod and for 2 months after discontinuation.
Objective: To present updated cumulative data on pregnancy outcomes in women exposed to fingolimod.
Methods: Pregnancy outcomes were collected from fingolimod clinical trials, Novartis post-marketing safety database, and the Multinational Gilenya™ (fingolimod) Pregnancy Exposure Registry.
Results: As of 28 Feb 2013, 280 pregnancies were reported where the patients became pregnant while on fingolimod or within 2 months of treatment discontinuation (238 prospective cases and 42 retrospective cases). Of these, 65 (23%) had normal births, 76 (27%) had abortions (49 induced and 27 spontaneous without abnormalities), and the outcome is unknown for 128 pregnancies (46% with 51 on-going, 48 outcome unknown and 29 lost to follow-up). A total of 11 adverse pregnancy events have been reported: premature baby with congenital posteromedial bowing of tibia; acrania; Fallot’s tetralogy; pyloric stenosis; premature baby with atrial septal defect; bilateral vesicoureteric reflux; mild renal dysplasia; macrosomia; inguinal hernia; premature baby with multiple complications related to prematurity; premature baby (34 2/7 week) with no complication related to prematurity. As of 28 Feb 2013, the pregnancy registry has been launched in 10 countries with 15 women enrolled. Updated data will be presented including data from the Novartis sponsored pregnancy registry.
Conclusions: Available data do not allow firm conclusions about the risk of fingolimod exposure during pregnancy. The registry will continue for at least 6 years and gather information on up to 500 pregnancies.
Kerstin Hellwig got speaker honoraria and research support from Bayer, Schering Healthcare, Teva, Sanofi Aventis, Biogen Idec, Merck Serono and Novartis Pharma.
Gideon Koren receives consultant fees from Novartis as a member of Gilenya Pregnancy Advisory Board
Helmut Butzkueven has served on scientific advisory boards for Biogen Idec, Novartis, Merck Serono and Sanofi- Aventis and has received conference travel support from Novartis, Biogen Idec, Merck-Serono and Sanofi Aventis. He serves on steering committees for trials conducted by Merck Serono, Biogen Idec and Novartis. Dr Butzkueven has received research support from Merck Serono, Novartis and Biogen Idec in his capacity as honorary chair of the MS Base Foundation. He is on the editorial board of Multiple Sclerosis International and Multiple Sclerosis and related disorders. He is the current recipient of a National Health and Medical Research Council (NHMRC) Career Development Award (628856), NHMRC Project Grants (566513, 628799, 1009757), NHMRC Centre of Excellence Award (1001216), an Australian Research Council Linkage Grant (LP110100473)RG and a National MS Society (USA) Project Grant (RG3850A3/1).
Hugh Tilson consults widely with the multi-national pharmaceutical industry, including service on several global pregnancy and disease registries. He also serves as an advisor to FDA, HRSA, and the WHO Collaborating Centres on Drug Safety matters.
Sonia Hernandez-Diaz provides consultation to Novartis and AstraZeneca. The pharmacoepidemiology program at Harvard has been supported by unrestricted training grants from Pfizer and Novartis
Tom MacDonald: His dept. holds research grants from Novartis, Pfizer, and Ipsen & Menarini. I am or have been the principal investigator on trials paid for by: Pfizer, Novartis, Ipsen & Menarini. I have been paid Consulting or speakers fees by Pfizer, Novartis, Kaiser Permanante, Takeda, Recordati, Servier, Menarini, NiCox & AstraZeneca.
Elena Kornyeyeva is an employee of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Estel Plana is an employee of Novartis Farmaceutica S.A., Spain
Yuanyuan Lu, Malika Cremer, Rajeev K. Amar, Rolf Schlosshauer, William Collins, Yvonne Geissbuehler, and Goeril Karlsson are employees of Novartis Pharma AG, Basel, Switzerland