Most MS therapies not associated with worst pregnancy outcomes

Researchers report that most treatments for pregnant women with MS (multiple sclerosis) do not lead to increased risks of major adverse outcomes.

“We found that most therapies were not associated with an increased risk of miscarriage, premature birth or major birth defects,” said Professor Kerstin Hellwig from the Department of Neurology at Ruhr University Bochum, Germany.

Hellwig added, “Due to the small number of cases in pregnancies with cladribine, teriflunomide and alemtuzumab exposure, we are unable to draw any definite conclusions about rare events such as congenital defects or severe infections.”

The researchers published their findings in The Lancet Regional Health Europe on December 24, 2024.

They evaluated data from the German Multiple Sclerosis and Pregnancy Registry recorded between November 2006 and June 2023. This included 2,885 pregnancies in which mothers had received a disease-modifying therapy (DMT), including interferons, glatiramer actate, dimethyl fumarate, teriflunomide, S1P modulators (fingolimod, ponesimod), alemtuzumab, natalizumab, anti-CD20 antibodies (rituximab, ocrelizumab, ofatumumab) and cladribine.

And 837 pregnant women with MS in the registry and the study had not received any medication for MS.

“This cohort is one of the largest in the world,” said Hellwig. “It has a high variability of exposure to the different immunotherapies. Most of the women had only received medication in the first trimester of pregnancy.”

The investigators reported that in 2,885 DMT-exposed and 837 DMT-unexposed pregnancies, exposure was not associated with an increased risk of  spontaneous abortions, preterm births or major congenital anomalies (MCAs).

Severe infections were rare, but more often in the Fumarates-group (11/395: 2.8% vs. 8/837 unexposed-group (p-value: 0.03).

Antibiotic-use was associated with 2nd-trimester (p-value: <0.001), 3rd-trimester Natalizumab-exposure (p-value: 0.01), and anti-CD20-exposure (p-value: <0.001).

Birthweight was significantly reduced in the Sphingosine-1-phosphate-group (p-value: <0.001), and 3rd-trimester Natalizumab-subgroup (p-value: 0.02).

Small for gestational age (SGA) newborns were common in the Sphingosine-1-phospate-subgroup (p-value: 0.02) and anti-CD20-group (p-value: 0.04), and in the whole study cohort (651/3459: 18.8%), exceeding the general German population rate (10%) (p-value: <0.001).

The authors concluded, “We observed an increased SGA [Small for gestational age] risk, especially following highly-effective DMTs, although the pathomechanisms remain unclear. More research is needed on infection risks and MCAs [major congenital anomalies], perhaps by linking different registries.”