No apparent harm seen with early pregnancy ozanimod exposure, but caution still urged

Exposure to ozanimod during early pregnancy does not appear to pose risks of adverse pregnancy outcomes and foetal health despite recommendations to avoid getting pregnant while receiving ozanimod and for 3 months after treatment discontinuation, according to a study.

The analysis was based on data from the ozanimod clinical development program, where 78 pregnancies were documented among 14 participants with ulcerative colitis (UC), six with Crohn’s disease (CD), 57 with relapsing multiple sclerosis (RMS; 58 outcomes due to twins), and one healthy volunteer. Ozanimod exposure occurred during the first trimester for all participants, with medication withdrawn promptly upon confirmation of pregnancy, except for those who chose to terminate their pregnancy and remained on study medication. [AIBD 2023, abstract S6]

Spontaneous abortion occurred in 15 percent of pregnancies. Meanwhile, 10 percent of pregnancies led to preterm delivery.

In the UC group, seven pregnancies resulted in live births with no congenital abnormalities or premature births. There were three cases of spontaneous early pregnancy loss and four elective terminations.

The CD group, on the other hand, had two live births with no congenital abnormalities or premature births, one spontaneous early pregnancy loss, one ongoing pregnancy, and two with no information. The RMS group had 33 live births (including one with duplex kidney and four premature births), eight spontaneous early pregnancy loss (a twin pregnancy led to one early loss and one live birth), 10 elective terminations, five ongoing pregnancies, and two with no information.

Finally, the healthy volunteer had elective termination.

“The estimated exposure in female partners relative to male [partners] was 0.03 percent for ozanimod and 0.025 percent each for [the metabolites] CC112273 and CC1084037,” reported senior study author Dr Marla Dubinsky, co-director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai in New York City, New York, US.

In other words, female partners of individuals taking ozanimod are likely exposed to very small amounts of the drug and its byproducts, which do “not represent a clinically meaningful risk to partners or potential embryos,” as Dubinsky pointed out.

An oral medication targeting sphingosine 1-phosphate (S1P) receptors 1 and 5, ozanimod is indicated for the treatment of moderate-to-severe UC and RMS in many countries and is currently being tested for CD. Given the involvement of S1P receptors in embryonic blood vessel formation, the use of ozanimod and other S1P modulators come with contraception guidelines and general warnings about potential foetal harm based on data from preclinical studies.