No Increased Risk Found From Ocrevus Exposure in Pregnancy

Exposure to Ocrevus (ocrelizumab) just before conception or during the first three months of pregnancy does not seem to increase the risk of adverse outcomes for women with multiple sclerosis (MS) or their babies, according to a small Australian study.

All of the patients stopped taking Ocrevus upon finding out they were pregnant, but B-cell levels remained low for most of the women over an average 16-month treatment interruption — and none experienced a relapse.

“We did not identify any concerning major safety signals among the patients who were exposed to [Ocrevus] prior to conception or during the first trimester of pregnancy,” the researchers wrote.

The study, “Pregnancy outcome following exposure to ocrelizumab in multiple sclerosis,” was published in Multiple Sclerosis Journal – Experimental, Translational and Clinical.

Women of childbearing age make up the largest proportion of MS patients, and possible pregnancy is an important consideration when choosing a course of treatment.

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Ocrevus is an MS antibody therapy, marketed by Genentech, that is approved for relapsing forms of the disease and for primary progressive MS. The treatment, given intravenously (into the vein) every six months, targets the CD20 protein on the surface of B-cells — an immune cell type implicated in MS progression — leading to their long-lasting depletion.

Animal studies suggest that Ocrevus exposure during pregnancy could cause B-cell depletion and toxicity in offspring. While the effects of Ocrevus in pregnant human MS patients have not been thoroughly evaluated, it has been suggested that Ocrevus raises the risk of serious infections that could result in miscarriage, preterm birth, or stillbirth.

The U.S. Food and Drug Administration currently recommends that pregnancy be avoided for at least six months after an Ocrevus infusion. In the European Union, the recommended interval is of at least one year.

To shed light on the potential effects of Ocrevus exposure during pregnancy, a pair of researchers in Australia retrospectively examined outcomes from 14 pregnancies among 12 MS patients between 2018 and 2020. Each of the expectant mothers had been exposed to Ocrevus within six months before conception or in the early months of pregnancy.

On average, the women were 34.8 years old and had been living with MS for a mean of 65 months, or longer than five years. Ocrevus was the first disease-modifying therapy given to four patients; the others had received other treatments before Ocrevus.

The majority of pregnancies (13 of 14) were exposed to Ocrevus in the six months prior to conception — at a mean of 14.2 weeks before conception. Three patients also received Ocrevus during the first trimester before discovering they were pregnant, at a mean of 5.7 weeks into the pregnancy.

Upon learning of their pregnancy, all of the patients suspended their Ocrevus treatment, and then were monitored for B-cell levels. Overall, Ocrevus treatment was suspended for a mean of 65 weeks, or just over 16 months.

Of the 14 pregnancies, 13 resulted in live births. The remaining pregnancy was voluntarily terminated after the detection of an unrelated genetic abnormality.

None of the 13 children were born preterm or had low birth weight. One child had a minor congenital abnormality, and another was born with mild, respiratory distress which resolved without treatment.

For a third infant, the mother developed oligohydramnios, a deficiency in the amount of amniotic fluid surrounding the baby during pregnancy, which occurred as a result of an insufficient or damaged placenta. The child required breathing assistance in the first days of life, had low blood sugar, and required antibiotics to treat sepsis — a severe, life-threatening response to infection.

While the cause of this complication was not determined, there are no previous reports of Ocrevus causing placental insufficiency. This potential relationship will need to be examined in larger studies, the researchers noted.

No serious adverse events, including infection or chorioamnionitis — an infection in the amniotic fluid that can affect both mother and child — were reported among the patients.

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In most of the women, B-cell levels remained suppressed during pregnancy without the need for further infusions. B-cell levels did increase in one patient, who required treatment with Tysabri (natalizumab), another approved MS therapy, throughout her pregnancy.

Another expectant mother’s B-cell levels increased two weeks before delivery, and she resumed Ocrevus treatment one week after childbirth.

No relapses were reported, and MRIs after delivery showed signs of stable disease despite the treatment interruption during pregnancy.

“Our data suggests that patients with MS who had been treated with [Ocrevus] before pregnancy experienced a stable MS disease course throughout pregnancy and during postpartum period despite a prolonged period of treatment interruption,” the researchers wrote.

Previous studies have found that only minimal amounts of ocrelizumab are detectable in breastmilk. Here, eight patients breastfed their infants, with four receiving Ocrevus treatment while nursing. No adverse effects were reported in breastfed infants exposed to Ocrevus.

“We did not observe increased adverse events in our [group] of patients who were exposed to [Ocrevus] prior to conception or during the first trimester of pregnancy,” the researchers concluded.

“In patients … who [develop] repopulation of B cells as the pregnancy [approaches] term, we suggest for timely re-dosing of [Ocrevus] soon after delivery to prevent a relapse. On the other hand, if reconstitution of B cells occurs at an early stage of pregnancy, our approach is to transition to an alternative high efficacy [disease-modifying treatment] which is considered safe in pregnancy,” they added.

One limitation of the study was the small number of patients, the team noted, adding that “future observational studies incorporating larger patient [groups] will be required to provide more robust data.”