A registry data analysis concluded that most disease-modifying therapies for MS are not associated with an increased risk of complications during pregnancy.

At the American Academy of Neurology Annual Meeting (AAN 2023), held from April 22 to 27, Nadine Bast, a pharmacist at St. Josef Hospital in Bochum, Germany, presented an analysis of registry data that concluded that most disease-modifying therapies (DMTs) for MS are not associated with an increased risk of complications during pregnancy. Although a few therapies were associated with slightly elevated rates of congenital abnormalities attributable to prenatal exposure, the small sample sizes in this particular cohort limited the strength of the conclusions, underscoring a need for future prospective research.

Although MS does not negatively influence most pregnancy outcomes, less is known regarding the effects of prenatal exposure to novel DMTs. Fetal safety is typically protected over maternal safety on most drug labels, which may mean that patients have to make tough choices about treatment during their pregnancy without much evidence-based information to support their decision. The objective of this study was to examine associations between neonate health outcomes and prenatal exposure to DMTs in birth cohorts in mothers with MS.

To address the impact of DMT use on pregnancy outcomes, Bast and colleagues analyzed 3,387 pregnancies from the German MS and Pregnancy Registry, of whom 2,639 were DMT-exposed at some point during the pregnancy. The other 748 fetuses were unexposed to DMTs, and served as the comparator. The researchers then split the cohort based on the types of therapy, with the larger group (n=1,671 pregnancies) having been exposed to older DMTs, such as glatiramer, teriflunomide, dimethyl fumarate, and interferon therapies. Bast explained, “These classes of DMT are thought to be less effective at delaying disease progression but are also less likely to cause side effects than newer therapies. The remaining 968 patients were treated with newer, relatively more effective therapies, including S1P modulators—mostly fingolimod—and CD20 antibodies, as well as cladribine, alemtuzumab, and natalizumab.”

There were differences at baseline between the groups, with more than 700 women taking interferon therapies while pregnant, compared with fewer than 20 participants on some of the other agents, which complicated statistical analyses. The researchers also found that maternal age at conception as well as alcohol or tobacco use also differed significantly. However, critical items of pregnancy complications, including miscarriage, ectopic pregnancy, and stillbirth, did not vary significantly between those taking any DMT and the patients not receiving DMTs.

Bast said: “When looking at health outcomes of the infants, rates of chromosomal abnormalities or death shortly after birth were very low across all groups and did not differ between DMT-exposed or unexposed patients. Furthermore, rates of major congenital abnormalities between DMT-exposed and unexposed babies did not vary significantly, although there were some notable numerical increases among babies exposed to some of the drugs (6%), when compared to the control non-exposed infants (3.5%). This raises the need for additional research, but the numbers are not statistically alarming.”

“Our data, however, do point to prenatal exposure to DMTs, both in older as well as newer classes of DMTs, resulting in significantly lower birth weights independent of gestational age than unexposed babies,” she added.

When asked what kind of conclusions could be drawn, Bast pointed out, “We only have a small sample size here, which limits our statistical power. However, future research on DMT use in pregnancy should focus on these medications, as well as additional types of S1P modulators and anti-CD20 therapies. We also have to keep in mind that patients who are prescribed higher efficacy DMTs might have more aggressive disease management to control their severe underlying disease, which could confound the results. All the groups, including unexposed babies, had higher rates of being abnormally small for their gestational age than would be expected in the general population.”

“We hope these findings may help patients faced with decisions about using treatments during pregnancy, although there are also additional aspects to be considered during family planning in women with MS. In order to combine information on rare exposure groups and recently approved medications, we need to harmonize the data collection between international groups to be able to merge the results and get a higher statistical power,” Bast concluded.