Glatiramer acetate exposure during the first trimester of pregnancy appears safe and was not associated with a teratogenic effect in a nationwide German Multiple Sclerosis and Pregnancy registry.
In the second largest study of the safety of glatiramer acetate exposure during early pregnancy in multiple sclerosis patients, Sandra Herbstritt, Pharm.D., and her colleagues at Ruhr University Bochum (Germany) reported that exposure to the drug in 151 women with multiple sclerosis was not associated with significant differences in pregnancy or birth outcomes when compared with 95 controls without exposure to disease-modifying therapy (DMT) during pregnancy. All but three of the patients who took glatiramer acetate stopped it in the first trimester (median duration of 31 days; range, 0-154 days). Pregnancies were considered exposed to glatiramer acetate if the last injection was administered after the last menstrual period (Mult Scler. 2016 Jan 11. doi: 10.1177/1352458515623366).
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Significantly more relapses occurred in women who did not take a DMT during pregnancy than in women who took glatiramer acetate (28 vs. 18, respectively), particularly in the first and third trimesters. A total of 224 live births occurred, including 136 with exposure to glatiramer acetate and 88 without DMT exposure. All but 3 of the 22 pregnancies that did not result in live births were spontaneous abortions in the first trimester.
The only early neonatal death among women who took glatiramer acetate involved an infant who died 30 minutes after birth in gestational week 24 because of a maternal infection. According to the investigators, “the mother received glatiramer acetate for 8 months prior to pregnancy, stopped treatment in the second [gestational week], and was not exposed to other substances during pregnancy.”
A total of nine congenital abnormalities (eight major, one minor) were observed without any specific pattern and included three in glatiramer acetate–exposed neonates and six in unexposed neonates.
No safety signals were reported for glatiramer acetate on the outcome of pregnancy, labor, or delivery in a previous meta-analysis of 97 pregnancies in eight studies. Glatiramer acetate’s manufacturer, Teva, reported no adverse outcomes in a conference abstract of 245 pregnancies exposed to glatiramer acetate, but the company has not published its postmarketing surveillance data in manuscript form, the authors wrote.
“Our results of a lacking adverse effect of glatiramer acetate during early pregnancy exposure are biologically plausible as it is very unlikely that glatiramer acetate passes the placental barrier,” the investigators wrote, because it is not permeable for a large heterogeneous mixture of polypeptides such as glatiramer acetate, which have molecular weights of 5,000-9,000 d.
The German Multiple Sclerosis and Pregnancy registry was partly supported by Bayer Healthcare, Biogen Idec Germany, Merck Serono, Novartis Pharma, Teva Pharma, and Sanofi-Aventis Genzyme Pharmaceuticals, but the sponsors had no role in the registry design, data collection, analyses, or dissemination of results. Two authors reported financial ties to numerous pharmaceutical companies that market MS drugs, and two reported support from the German Research Council. Another author is the site principal investigator for two industry-sponsored randomized clinical trials.