DOP53 Pregnancy outcomes in the ozanimod clinical development program in relapsing multiple sclerosis, Ulcerative Colitis, and Crohn’s Disease
Dubinsky, M.C.(1);Mahadevan, U.(2);Charles, L.(3);Afsari, S.(3);Henry, A.(3);Comi, G.(4);Selmaj, K.(5);van der Woude, C.J.(6)
(1)Icahn School of Medicine, Pediatrics- Gastroenterology, Mount Sinai, United States;(2)University of California San Francisco, Gastroenterology, San Francisco, United States;(3)Bristol Myers Squibb, Global Drug Safety & Risk Mgmt, Princeton, United States;(4)San Raffaele Scientific Institute- Vita-Salute San Raffaele University, Department of Neurology, Milan, Italy;(5)Center for Neurology- Łódź- Poland and Collegium Medicum- University of Warmia and Mazury, Department of Neurology, Olsztyn, Poland;(6)Erasmus MC, Gastroenterology, Rotterdam, Netherlands Antilles
Background
Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, has demonstrated efficacy in patients with relapsing multiple sclerosis (rMS) and ulcerative colitis (UC), and is being studied in Crohn’s disease (CD). S1P1-3 receptors are involved in vascular formation during embryogenesis. Within studies in the ozanimod clinical development program, female participants of childbearing potential were required to use effective contraception while receiving and up to 3 months after discontinuing ozanimod; treatment discontinuation was required if pregnancy was confirmed. Here we review pregnancy outcomes data with ozanimod use in rMS, UC, and CD.
Methods
All pregnancies, including participant and partner pregnancies, in the ozanimod clinical development program with an initial diagnosis prior to a cut-off date of September 30, 2020 were assessed for pregnancy outcomes.
Results
At cut-off, safety data on 4131 participants were available. A total of 83 pregnancies were reported in the safety database of participants treated with ozanimod or their partners (Table). All pregnancy exposures occurred during the first trimester. Of the 60 pregnancies in ozanimod clinical trials, 9 were reported in patients with UC, and 3 in patients with CD. Participants discontinued study medication promptly except for those who elected pregnancy termination and did not discontinue study medication. Among all pregnancies in the ozanimod clinical development program, the incidence of spontaneous abortion in clinical trial participants was 15%; the rate in the general population is between 12% and 22%. The rate of preterm birth was 10.7% of live births; as reference, the global population estimate is 10.6% and the European estimate is 8.7%. No teratogenicity was observed. Outcomes in patients with UC included 2 live births that resulted in 2 full-term healthy newborns, 2 ongoing pregnancies, 2 spontaneous early losses, and 3 elective terminations.
Conclusion
While pregnancy should be avoided in patients on and 3 months after stopping ozanimod and clinical experience with ozanimod during pregnancy is limited, there has been no increased event of foetal abnormalities or adverse pregnancy outcomes seen with ozanimod exposure in early pregnancy.