Literature Review

Natalizumab May Be Associated With Increased Disease Activity During Pregnancy

The treatment appears not to increase the risk of spontaneous abortion or congenital anomalies.


Women with relapsing-remitting multiple sclerosis (MS) who discontinue natalizumab treatment before pregnancy may have increased disease activity, according to a study published March 6 in Neurology. In addition, taking natalizumab during the first trimester of pregnancy increases the risk of miscarriage, although the risk remains similar to that of the general population, according to an accompanying study.

An Analysis of Pregnancy Data

Emilio Portaccio, MD, of the Don Carlo Gnocchi Foundation in Florence, Italy, and colleagues analyzed data for all pregnancies between 2009 and 2015 in patients with MS who presented to 19 Italian sites. They compared data for 83 patients receiving natalizumab with those for 350 control patients who were receiving injectable immunomodulatory agents or no treatment. The investigators followed up with the women every six months, at each relapse, and at one year after birth.

The patients receiving natalizumab had 92 pregnancies. Approximately 37% of women receiving natalizumab had at least one relapse during pregnancy, compared with 10% of controls. Relapse rate during pregnancy was higher among patients whose last infusion occurred before the last menstrual period (55.9%) than among patients whose last infusion occurred after the last menstrual period (20%) or controls (10%). Receiving the last natalizumab infusion before the last menstrual period was the only predictor of relapse during pregnancy. In the first trimester after delivery, the rate of relapse was 21.7% in natalizumab-treated patients and 13.7% in controls.

Twelve patients had disability worsening at the end of the one-year follow-up. In 11 of these patients, disability accumulation resulted from relapses during pregnancy or after delivery. Disease progression was reduced in patients for whom medication was reintroduced earlier after delivery.

About 75% of pregnancies in women receiving natalizumab had treatment exposure, and the mean duration of exposure was 1.2 weeks. The odds ratio of spontaneous abortion was 3.9 among patients receiving natalizumab, compared with controls. The rate of spontaneous abortion among natalizumab-treated patients (17.4%) was similar to that observed for the general Italian population (14%), however. The rate of major congenital anomalies was 3.7% in patients exposed to natalizumab, 1.3% in patients exposed to interferon beta, and 0.9% in untreated patients. The differences between groups were not significant. Exposure to natalizumab and exposure to interferon beta were associated with a lower length of the newborn.

Relapse Severity Was Not Measured

One limitation of the studies is that the women treated with natalizumab may have been different from women not treated with natalizumab in ways that the investigators did not measure. In addition, the researchers did not measure relapse severity.

“Our findings suggest that if women who take natalizumab for MS want to become pregnant, it may be best to continue treatment up until a pregnancy test is positive and then at that point discontinue use,” said Dr. Portaccio. “While there is still a risk of increased disease activity, this course of action may lower that risk.”

—Erik Greb

Suggested Reading

Portaccio E, Annovazzi P, Ghezzi A, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology. 2018;90(10):e823-e831.

Portaccio E, Moiola L, Martinelli V, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: II: Maternal risks. Neurology. 2018;90(10):e832-e839.

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