The increase in sNfL is independent of relapses, which suggests that patients have increased subclinical disease activity during this period, according to the researchers.
Dr. Özgür Yaldizli
When the investigators controlled their data for exposure to disease-modifying therapy (DMT), the effect of pregnancy on sNfL was no longer evident. These data were presented said at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
The results suggest that “sNfL may qualify as a sensitive and minimally invasive measure of disease activity in pregnancy,” said Özgür Yaldizli, MD, consultant neurologist at University Hospital Basel (Switzerland). “Strategies allowing the continuation of DMT during pregnancy may be warranted.”
MS preferentially affects women in their reproductive years, said Dr. Yaldizli. Almost one-third of women with MS become pregnant after they receive their diagnosis. A decrease in disease activity is typical in the third trimester, as is an increase in relapse frequency post partum.
DMTs reduce the risk of relapse, but have potential side effects for the woman and the fetus. Some DMTs are immunosuppressants, and they increase the risk of infection during pregnancy. Other DMTs may harm the development of the fetus, particularly if administered early during pregnancy.
“There is an urgent need to identify patients with high disease activity during pregnancy,” said Dr. Yaldizli. Increased levels of NfL, a specific biomarker of neuroaxonal injury, are associated with relapses, MRI activity, and disability worsening among patients with MS. Response to DMT is associated with decreased NfL levels. But few data about sNfL during pregnancy or post partum are available.
Relapses were associated with increased sNfL
Dr. Yaldizli and colleagues examined data from the Swiss MS Cohort Study to describe DMT use before, during, and after pregnancy. They also sought to assess sNfL as a marker of disease activity during and after pregnancy and to evaluate whether interrupting DMT because of pregnancy leads to increased sNfL levels.
Eligible participants had prospectively documented pregnancies, and Dr. Yaldizli’s group excluded pregnancies with early termination from their analysis. Serum samples were collected every 6 or 12 months and analyzed using the Simoa NF-light assay. The investigators used univariable and multivariable mixed-effects models to investigate associations between clinical characteristics and longitudinal sNfL levels in women before pregnancy, during pregnancy, and post partum.
Dr. Yaldizli and colleagues included 72 pregnancies in 63 patients with relapsing MS in their analysis. Nine patients had two pregnancies during follow-up. The population’s median age was 31.4 years, and median disease duration was 7.1 years. Median Expanded Disability Status Scale (EDSS) score at last visit before birth was 1.5. Median follow-up time was 6 years.
Most patients were treated with DMT before or during pregnancy. For most patients (39), fingolimod or natalizumab was the last DMT given before birth. Four patients did not use DMT before, during, or after pregnancy. In 14 pregnancies, the patient continued DMT for more than 6 months.
The univariable analysis showed that sNfL levels were 22% higher during pregnancy, compared with outside the pregnancy and postpartum period. The investigators recorded 29 relapses during the pregnancy and postpartum period. Relapses were more likely to occur during the first trimester and the first 3 months post partum. In the multivariable analysis, relapses that occurred within 120 days before serum sampling were associated with 98% higher levels of sNfL. In addition, sNfL was 7% higher for each step increase in EDSS and 13% higher during the pregnancy and postpartum period, compared with outside of that period.
When the investigators included DMT exposure at sampling time in the model, however, the pregnancy and postpartum period no longer had an effect on sNfL. The sNfL levels were 12% lower among patients exposed to DMT, compared with patients without DMT exposure.
Some DMTs, such as interferon-beta, are relatively safe during pregnancy, but the greater the medication’s efficacy, the more problematic it can be, said Dr. Yaldizi. “There are medications that are given, for example, every 6 months, like ocrelizumab. There are other medications that have to be taken daily. Probably the safest medications are those that are not given so often during pregnancy.”
Future research should examine the escalation therapies (i.e., the newer and more effective DMTs) during pregnancy in patients with MS, he added. “Not only in pregnancy, but also in general, we have to look for ways to measure disease activity in patients who switch therapy, who deescalate therapy.”