Pregnant Women With MS Show Increased NfL

Serum neurofilament light (NfL) levels rose in women with multiple sclerosis (MS) during pregnancy and postpartum periods when no disease-modifying treatment (DMT) was used, researchers reported.

This rise in NfL, a measure of axonal injury, was independent of MS relapses, suggesting increased subclinical disease activity during this time, said Özgür Yaldizli, MD, of University of Basel in Switzerland, at a late-breaking session of MS Virtual 2020, the joint ACTRIMS-ECTRIMS meeting.

There’s an urgent need to identify patients with high disease activity during pregnancy, Yaldizli noted.

“Neurofilament light may qualify as a sensitive and minimally invasive measure of disease activity during pregnancy,” he told MedPage Today. “We think that strategies to continue DMT during pregnancy, at least in selected patient groups, are warranted.”

Pregnancies among women with MS have risen in the U.S. Research has shown that relapse rates tend to decline during pregnancy, especially in the third trimester, and increase during the first 3 months postpartum before returning to pre-pregnancy rates.

“According to natural history cohorts, about one-third of pregnant MS women experience a relapse within 3 months postpartum,” Yaldizli said. “DMTs can reduce the risk of relapses, but have potential side effects for the fetus and woman.”

One of the dilemmas neurologists face with MS patients who want to become pregnant is what to do about disease-modifying therapy, noted Jeffrey Cohen, MD, of the Cleveland Clinic in Ohio, who wasn’t involved with the study.

“This study provides some input on how one could monitor a woman while she’s trying to get pregnant,” Cohen said in a press briefing before the presentation. “In general, the use of NfL to monitor disease activity is something that we’re going to see more and more of in clinical practice.”

For their analysis, Yaldizli and colleagues systematically followed 72 pregnancies in 63 relapsing MS patients from the Swiss MS Cohort. Most patients stopped DMT after they received a positive pregnancy test. Patients were evaluated every 6 or 12 months through serum samples and MRI; a total of 433 serum samples were collected.

Participants had an average age of 31, mean disease duration of 7.1 years, and a median Expanded Disability Status Scale EDSS score of 1.5, indicating no disability but minimal signs in more than one functional system. Most patients were treated with DMT before or during pregnancy; four patients had no treatment before, during, or after pregnancy. Most were treated with fingolimod (Gilenya; 19 patients) or natalizumab (Tysabri; 20 patients) as their last MS medication before giving birth.

Relapses occurred more frequently in the first trimester and first 3 months postpartum. NfL levels increased toward the last trimester and first 3 months postpartum, not just in women who experienced relapses.

In univariable analysis, NfL was 22% higher during, compared with outside, the pregnancy-postpartum period (β 1.218, 95% CI 1.10-1.35, P<0.001).

In a mixed-effects model including age, recent relapse, and EDSS, patients had higher NfL values during pregnancy or the DMT-free postpartum period compared with before or after this time. This association lost significance when including DMT exposure at serum sampling into the model, indicating that women on DMT had lower NfL values during pregnancy, Yaldizli said.

“This study does not prove that every pregnant woman should be treated with disease-modifying treatment during pregnancy. It is not a randomized controlled trial,” he noted.

“However, based on our study using real-world data, pregnant women on disease-modifying treatment have lower NfL levels in serum and lower risk for relapses during pregnancy and postpartum. A limitation is that we had a relatively small number of serum samples in the last trimester of the pregnancies.”