Natalizumab cessation linked with pregnancy-related MS relapses in women

Pregnancy-related MS relapses were associated with early natalizumab withdrawal among women before and during pregnancy, according to a study published in JAMA Network Open.

“There is a substantial risk for disease activity reactivation, even for women who stop the treatment early during the first trimester, including a relevant risk for functional ... disability including rare cases of catastrophic relapses,” Kerstin Hellwig, MD, of the department of neurology at Ruhr University Bochum in Germany, told Healio. “I think it also interesting that the early (in the first 4 weeks) reintroduction of natalizumab did not reduce the postpartum relapse risk.”

Hellwig and colleagues designed the prospective cohort study to assess the association between early natalizumab withdrawal before or during pregnancy with risk for severe relapses and relapse-related disability.

Using the German Multiple Sclerosis and Pregnancy Registry, they evaluated 274 pregnancies of women who stopped natalizumab treatment within the 2 years before or in the first trimester of pregnancy between November 2006 and February 2018. Participants completed questionnaires at enrollment, during each remaining trimester and at 1, 3, 6 and 12 months postpartum.

A total of 66.78% of the cohort reported relapses during pregnancy and the postpartum year, 16.05% reported severe relapses, and 1.1% reported potentially life-threatening relapses. Further, 10.58% of pregnancies reportedly resulted in significant relapse-related disability. The researchers also reported that relapses were common during both pregnancy (39.78%) and postpartum (49.27%).

The study did not associate pregnancy (adjusted HR = 0.9; 95% CI, 0.64-1.27) with a reduced relapse risk; exclusive breastfeeding (aHR = 1.34; 95% CI, 0.86-2.10) or restarting natalizumab treatment (aHR = 1.06; 95% CI, 0.48-2.36) also were not associated with reduced risk of early postpartum relapse 6 months after delivery. However, researchers did find that the relapse rate was lower during the 12 months postpartum in women who restarted natalizumab within the first 4 weeks after giving birth (aHR = 0.49; 95% CI, 0.28-0.86).

Although previous studies have reported the highest relapse risk during the first trimester, this study found the highest risk during the second trimester.

“In this cohort study, we found that the risk of relapse-related disability following natalizumab cessation for pregnancy was high, and the risk of catastrophic relapses appeared to exceed the risk of natalizumab-associated progressive multifocal leukoencephalopathy,” Hellwig and colleagues wrote. “The continuation of natalizumab during pregnancy or the use of depleting agents both show promising results in first studies. These treatment options should be evaluated with consideration for the best time to stop natalizumab during pregnancy and restart after delivery.”