Can MS Patients Safely Stay on DMTs During Pregnancy?

Modern disease-modifying drugs (DMTs) have revolutionized the treatment of relapsing-remitting multiple sclerosis (MS). However, their use during pregnancy has long been concerning. 

A study published in The Lancet Regional Health – Europe provides valuable insights into the safety of these medications during pregnancy, based on data from the German MS and Pregnancy Registry.

This study confirms that beta-interferons and glatiramer acetate are safe for use during early pregnancy. In addition, fumarate is likely a safe treatment option during pregnancy, and natalizumab and CD20 antibodies are viable treatment options for women with highly active MS.

In an interview with Medscape Medical News, Wolfgang Paulus, MD, from the Reproductive Toxicology Advisory Center at the University Women’s Clinic in Ulm, Germany, emphasized, “Patients with MS are often women of childbearing age who face the dilemma of needing effective therapy to prevent MS damage while also wanting to have children. They often feel uncertain about continuing to take MS medications during pregnancy. This study is therefore very valuable.”

Limited Data

Safety data on the use of many DMTs approved in recent decades in pregnancy remain limited. The European Medicines Agency (EMA) requires outcome data from at least 1000 pregnancies with first-trimester exposure to a given therapy. To date, this threshold has been met by only beta-interferons and glatiramer acetate.

According to the EMA, natalizumab does not increase the risk for teratogenic effects during the first trimester. This finding was highlighted by the Lancet study’s authors led by Nadine Bast, from the Neurological Clinic at St. Josef Hospital, Ruhr University Bochum in Bochum, Germany. 

In the past, many patients discontinued immunomodulatory medications after learning that they were pregnant. Patients often waited to see if a flare-up occurred, before treating it with methylprednisolone or prednisolone in the form of shock therapy for 3-5 days. This approach is feasible because immune processes and autoimmune diseases, such as MS, tend to be less active during pregnancy. 

Continuing Therapy

“This is still done in some cases, but it is no longer the treatment of choice,” Paulus stated. “Women with MS need effective treatment options during pregnancy, particularly those with highly active forms of the disease, as relapses often occur when the medication is stopped.”

Paulus advised that patients who are well-controlled on well-researched medications such as beta-interferons, glatiramer acetate, or natalizumab should continue therapy.

Pregnancy Outcomes

Bast and colleagues analyzed 2885 DMT-exposed pregnancies and 837 DMT-unexposed pregnancies between 2006 and 2023. The encouraging findings indicate that women who continued DMTs during pregnancy did not experience higher rates of spontaneous abortions (fetal loss before the 22nd week), preterm births (before the 37th week), or severe congenital malformations in their children. Women treated with teriflunomide had a higher preterm birth rate (21.9%) than those in the untreated group (9.3%).

Growth Restrictions

Babies born to mothers treated with S1P modulators or CD20 antibodies are more likely to be small for gestational age (SGA). 

The study found that these babies had lower birth weights (132 g less) and shorter heights (0.91 cm shorter) than those not exposed to these treatments. Similarly, lower birth weight (−74 g) was noted in babies whose mothers received natalizumab during the third trimester of pregnancy.

“Whether these growth restrictions are due to the DMTs or other factors cannot be determined from this registry data,” Paulus explained.

He suggested that the underlying disease might also have played a role, adding, “That would seem the most plausible to me in this context.” 

These findings are supported by data from the general German population, where the SGA rate is approximately 10%. In comparison, SGA rates were significantly higher in the overall cohort (18.8%), in those treated with highly effective DMTs (22.0%), and in the untreated group (17.6%).

When comparing birth weights, both the overall cohort and the untreated cohort (girls only) had worse outcomes than the general population.

“Growth restriction does not mean that the children suffer long-term damage. This should not be overestimated; it is not comparable to a malformation or a premature birth in the 28th week,” Paulus emphasized.

Congenital Malformations

Severe congenital malformations were observed in 3.8% of children with a 12-month follow-up period. No significant differences were noted between the treated and untreated pregnancies. However, the incidence of congenital malformations was numerically higher in the teriflunomide (12.0%) and alemtuzumab (10.5%) groups, according to Bast and colleagues.

“The number of cases of these substances is too small to make a reasonably reliable statement,” Paulus explained. “Since problems have already been seen with these substances in animal experiments, patients are informed in advance that they must not become pregnant while taking them, so this happens very rarely.”

Infection Risks

The researchers also analyzed the occurrence of serious infections and the use of antibiotics during pregnancy. Serious infections were rare (1.6%) but more common in the fumarate group (2.8% vs 1.0%) and the alemtuzumab group (9.1 vs 1.0%) than in the untreated group. Systemic antibiotics were administered more commonly during the second and third trimesters in women receiving natalizumab therapy and in those treated with CD20 antibodies.

“Further data from extended follow-up studies on the risk of maternal/infant infection [are needed],” Bast and her colleagues wrote. They noted that, despite being generally safe, fumarates were unexpectedly associated with higher infection rates.

Further research is needed to determine how quickly the weight of children with retardation of fetal growth returns to normal and whether these effects on growth are due to disease activity or DMTs. This is crucial for improving the recommendations for patients with highly active MS.

This story was translated fromMedscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.