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PHOENIX — Two new datasets support the use of potent disease-modifying therapies (DMTs) during pregnancy in women with active multiple sclerosis (MS), reinforcing a growing shift toward treatment when the potential benefit to the mother outweighs the risks.

Both studies — one involving the anti-CD20 monoclonal antibody ofatumumab and the other the integrin receptor antagonist natalizumab — are observational, but they provide a foundation for taking a proactive rather than reactive approach to treating pregnant women with active MS, said Riley M. Bove, MD, associate professor of neurology, University of California San Francisco.

Bove emphasized that a “we-don’t-know” approach is no longer acceptable when counseling pregnant women with active disease. As first author of the ofatumumab study — presented on May 29 at Consortium of Multiple Sclerosis Centers (CMSC) 2025 Annual Meeting— she followed up with a lecture the next day, explaining that evidence is now available to guide treatment decisions.

Relevant Data 

While significant knowledge gaps remain about the relative risks of DMTs to fetal development and pregnancy outcomes, it is well established that women with active disease “will be harmed if we do not help,” Bove said.

She and others now believe that the available data, even if observational, are relevant and useful in guiding decisions that affect both maternal and fetal health.

The new data on ofatumumab and natalizumab offer a clear example.

In an ongoing registry, ofatumumab exposure has been documented in 669 pregnancies.

Of these, 221 were reported prior to 2023, allowing for assessment of both short- and long-term outcomes. In most cases (87%), exposure occurred during the first trimester.

Adverse outcomes were reported, including spontaneous abortions in 12.6% of cases, preterm births in 9.6%, and minor congenital malformations in two infants (< 1%).

However, these rates are “in line with the background rates observed in the general population,” Bove noted. She emphasized that such data are important when weighing treatment decisions against the known risks of active disease, which can lead to irreversible brain injury in the mother.

The natalizumab data, presented as a late-breaking abstract at CMSC on May 30, reflected 16 years of experience at a single center. Tracking began in 2008, when two pregnancies were identified in women already receiving natalizumab.

Through 2024, no increased risk for adverse pregnancy outcomes was observed, while natalizumab treatment was associated with meaningful improvements in MS disease control.

A total of 58 pregnancies in 43 women have been tracked at the Rocky Mountain MS Clinic in Salt Lake City, according to Katrina Bawden, FNP-C, a nurse practitioner who has been involved since the registry began.

Reevaluating Natalizumab

She noted that outcomes were analyzed in women who discontinued natalizumab after learning they were pregnant as well as those who continued treatment into the third trimester.

Among the 38 pregnancies in which natalizumab was stopped, 13 women experienced clinical relapses, and four others showed new lesions on MRI. In contrast, among the 20 pregnancies where treatment was continued, there were no relapses and no MRI evidence of disease activity.

Pregnancy complications were observed, including one fetal malformation and 10 miscarriages, but Bawden noted that these figures — like those in the ofatumumab registry — are consistent with background rates.

“Of the three fetal deaths, all occurred in those who discontinued natalizumab,” she said. She noted that all 10 of the women who miscarried had healthy term full term deliveries in a subsequent pregnancy while remaining on natalizumab.

Compared to the start of the tracking period, Bawden said the data have prompted clinicians at her clinic to reevaluate the benefit-risk balance of using natalizumab during pregnancy.

“Women at the Rocky Mountain MS Clinic who become pregnant while treated with natalizumab, using shared decision-making, are now given the option of continuing natalizumab every 8 weeks throughout pregnancy with the last dose scheduled at 34 weeks’ gestation,” Bawden said.

‘Illogical Guidance’

Caring for pregnant women with MS is a complex challenge, given the incomplete information available. However, Bove — co-author of a 2024 paper on practical considerations for weighing the risks and benefits of DMT use during pregnancy — said that strictly following drug labeling is not helpful in guiding clinical decisions.

She noted that current recommendations are inconsistent across drug classes, vary between the FDA and the European Medicines Agency, and often fail to reflect the latest science — resulting in guidance that is ultimately “illogical.”

Moreover, labeling continues to evolve, and pregnancy-related use of DMTs remains a dynamic area, with new data — such as the recent studies presented at CMSC — shaping clinical strategies.

Bove emphasized that it is the clinician’s responsibility to stay informed as the evidence develops, in order to support shared decision-making. This includes staying up to date on when to treat active disease during pregnancy, when to restart therapy if it was paused, and how to weigh the benefit-risk profile of DMTs for women who choose to breastfeed.

When making MS treatment decisions during pregnancy, the adage “first, do no harm” has traditionally focused on fetal risk. But Bove pointed out that withholding treatment may, in many cases, pose greater harm to the mother, underscoring the need for a balanced discussion that considers risks to both mother and fetus.

Bove reported financial relationships with Alexion, Biogen, Genentech, Horizon, Janssen, Merck, Novartis, Roche, Sanofi, and TG Therapeutics. Bawden reported financial relationships with Amgen, ANI Pharmaceuticals, Sanofi, TG Therapeutics, and Biogen, which provided funding for assembling the data she presented.