Serum neurofilament light offers effective measure of MS disease activity during pregnancy

Serum neurofilament light chain levels increased during pregnancy and the postpartum period among women with MS in the Swiss MS Cohort study, according to findings presented during an encore session of MSVirtual2020.

The study results also demonstrated that disease-modifying treatment (DMT) eliminated the impact of pregnancy on neurofilament light (NfL) levels.

“MS preferentially affects women in their reproductive years. Pregnancy in MS typically goes along with reduced disease activity during pregnancy, especially in the third trimester, followed by an increase in relapse frequency postpartum,” Özgür Yaldizli, PD, of the department of neurology at University Hospital Basel in Switzerland, said during his presentation. “DMTs are able to reduce the risk for relapses. However, they have potential side effects for the fetus and the woman. There is an urgent need to identify patients with high disease activity during pregnancy.”

Levels of serum NfL (sNfL) represent a specific biomarker for neuroaxonal injury, according to the researchers. Increased sNfL levels are associated with relapses and MRI activity, while the use of DMT correlates with a decline in NfL. Yaldizli and colleagues examined prospectively documented pregnancies in the Swiss MS Cohort Study to determine whether interrupting DMT because of pregnancy correlated with greater NfL levels in MS.

Yaldizli and colleagues obtained serum samples every 6 or 12 months and analyzed them with the Simoa NF-light assay. They used univariable and multivariable mixed effect models to examine relationships between clinical characteristics and longitudinal NfL levels.

The researchers looked at 72 pregnancies in 63 patients with relapsing MS (median age, 31.4; median disease duration, 7.1 years; median Expanded Disability Scale Status [EDSS] at last visit before birth, 1.5). Nine patients had two pregnancies. Researchers analyzed 433 samples, including 92 during pregnancy or up to the start of DMT through no more than 9 months postpartum (the pregnancy/postpartum period), 167 before the start of the pregnancy/postpartum period and 174 after the pregnancy/postpartum period.

Four patients had no DMT before, during and after pregnancy. DMT was maintained in 13 of 72 pregnancies (> 6 months during pregnancy: 6 rituximab/ocrelizumab, 4 natalizumab, 1 interferon-beta 1a intramuscular, 1 fingolimod and 1 glatiramer acetate).

In univariable analysis, the researchers observed NfL levels that were, on average, 22% higher during the pregnancy/postpartum period compared with outside that period (beta, 1.22; 95% CI, 1.10-1.35).

Multivariable analysis demonstrated that relapses within 120 days of serum sampling correlated with 98% higher NfL (beta, 1.98; 95% CI, 1.75-2.25). Each EDSS step increase corresponded with 7% greater NfL (beta, 1.07; 95% CI, 1.01-1.12), which was, on average, 13% higher during the pregnancy/postpartum period vs. outside that period (beta, 1.13; 95% CI, 1.03-1.24).

Most patients were treated with DMT prior to, or during, pregnancy, but discontinued treatment following a positive pregnancy test, Yaldizli said during his presentation. More than half of the patients in the study (n = 39) received fingolimod or natalizumab as the last medication prior to giving birth, he continued. In 39 of the pregnancies, women received DMT in the first two trimesters; in 15 pregnancies, women stopped DMT prior to becoming pregnant, Yaldizli said.

The impact of the pregnancy/postpartum period on NfL disappeared after the researchers inputted DMT exposure in the model, according to the study findings (beta, 1.07; 95% CI, 0.97-1.18). Samples obtained during DMT had, on average, NfL levels that were 12% lower than those not obtained during DMT (beta, 0.88; 95% CI, 0.79-0.98).

“Higher sNfL levels were found during pregnancy and the DMT-free postpartum period. This increase was independent of relapses, suggesting increased subclinical disease activity during this time span,” Yaldizli said. “sNfL may qualify as a sensitive and minimally invasive measure of disease activity in pregnancy.”