MS Research Examines PPD, Ozanimod in Pregnancy

October 24, 2020
AJMC Staff
AJMC Staff

Two abstracts presented at a recent multiple sclerosis meeting examined depression in pregnancy and pregnancy outcomes in ozanimod trials.

A pair of abstracts recently presented at a multiple sclerosis (MS) meeting looked at aspects of MS in pregnancy, with one examining associations of depression in pregnancy and one looking at outcomes when ozanimod is taken early in pregnancy.

In one abstract, researchers evaluated the prevalence of peripartum depression (PPD) in women with MS as well as risk factors for PPD in MS.1

PPD is defined as depression in late pregnancy to 1 year postpartum and occurs in 7% to 19% of women.

Researchers conducted a retrospective analysis of clinical data in the electronic health records of women with MS followed at the UCSF Multiple Sclerosis and Neuroinflammation Center.

The women, who became pregnant from 2015 to 2018, were identified in the electronic medical record; the primary outcome was PPD, as determined by the review of records.

Prevalence of PPD was estimated with logistic regression with generalized estimating equations (GEE), accounting for women with multiple pregnancies.

Univariable analyses with GEE logistic regression evaluated predictors of PPD (age, marital status, parity, delivery season, prematurity, birth weight, delivery mode, premorbid depression/anxiety, antidepressant discontinuation, sleep disturbance, and breastfeeding).

Multivariable analysis evaluated association between inflammatory disease activity (relapses in pregnancy/postpartum; gadolinium enhancing lesions postpartum); disease severity as assessed by the Expanded Disability Status Scale (EDSS); and PPD.

Out of 111 women, researchers identified 143 pregnancies with had live birth outcomes and known PPD status.

The mean age was 33; most of the women (93%) had relapsing remitting MS; 7% had clinically isolated syndrome; and 45% had premorbid depression.

PPD was present in 12.6% (95% CI, 7.3-17.8) of pregnancies.

According to univariable analyses, statistically significant factors linked with PPD included older age (odds ratio [OR], 1.16; 95% CI, 1.03-1.32 for 1-year increase); primiparity (OR, 4.02; 95% CI, 1.14-14.23); premorbid depression (OR, 3.70; 95% CI, 1.27-10.01); postpartum sleep disturbance (OR, 3.23; 95% CI, 1.17-8.91); and breastfeeding difficulty (OR, 3.58, 95% CI, 1.27-10.08).

But multivariable analyses showed only 3 factors linked with PPD:

maternal age (OR, 1.17; 95% CI, 1.02-1.34); primiparity (OR, 8.10, 95% CI, 1.38-47.40); and premorbid depression (OR, 3.89; 95%, CI 1.04-14.60).

MS-specific factors—relapses, MRI activity, and EDSS—were not linked with PPD. In other words, PPD in MS was similar to the general population, the authors said, “but was likely underestimated due to lack of standardized screening.” Since PPD could influence self-management of MS, they called for prospective evaluation with PPD screening.

Another abstract looked at outcomes when ozanimod was used during early pregnancy.2

Ozanimod was recently approved in the United States and the European Union for the treatment of relapsing forms of multiple sclerosis. There is limited knowledge of ozanimod during pregnancy; the labeling notes that it should be avoided during pregnancy and that women who may become pregnant should use contraception. Because it takes 3 months for the drug to clear, pregnancy should continue to be be avoided for 3 months after stopping treatment.

Ozanimod is a sphingosine-1-phosphate (S1P) receptor modulator; the S1P receptor is involved in vascular formation during embryogenesis.

Animal safety studies with S1P modulators have shown embryo-fetal toxicity, including embryo-fetal deaths and visceral malformations.

Given the limited clinical experience with ozanimod during pregnancy, the current study sought to review what is known about pregnancy outcomes data in the ozanimod clinical development program in relapsing multiple sclerosis. In ozanimod trials, females with childbearing potential are required to use effective contraception while receiving treatment and up to 3 months after discontinuing ozanimod, as well as to stop ozanimod if pregnancy is confirmed.

Pregnancy outcomes were assessed in cases reported from all multiple sclerosis studies in the ozanimod program and diagnosed by December 31, 2019. Pregnancy outcomes through June 15, 2020 were reported.

Forty-two pregnancies were reported among 1868 women taking ozanimod, with 26 live births. Of the 26, 20 were normal and 3 were premature but normal infants. There was 1 report each of neonatal icterus, late intrauterine growth retardation with subsequent normal progress over the first year, and duplex kidney (common variant in 1.8% of births).

There were 9 elective terminations, 6 early spontaneous abortions (of which 1 was a loss of a twin), 1 pregnancy ongoing, and 1 subject refused consent to follow-up. The incidence of spontaneous abortion in clinical trial participants exposed to ozanimod (14%) is at the lower end of the expected rate of early pregnancy loss in the general population (12% to 22%; García-Enguídanos et al 2002).

The researchers said that “to date there has been no signal of an increased risk of fetal abnormalities or other adverse pregnancy outcomes seen with exposure in early pregnancy.”

Women are 4 times as likely to be diagnosed with MS than men.

References

1. Krysko K, Anderson A, Singh J, et al. Risk factors for peripartum depression in women with multiple sclerosis. Presented at: Presented at: Migraine Trust International Symposium. October 3-9, 2020. Abstract P1135.

2. Minton N, Henry A, Janjua G, Poli R. Pregnancy outcomes in the ozanimod multiple sclerosis clinical development program. Presented at: Migraine Trust International Symposium. October 3-9, 2020. Abstract P1133.