Pregnancy and Infant Outcomes in Women with Multiple Sclerosis Exposed to Glatiramer Acetate Therapy: An Extended 4-Year Safety Update.

Abstract

Background and objectives: While glatiramer acetate (GA) is generally considered safe during pregnancy and breastfeeding, long-term data, particularly for the 40 mg/mL dose, are limited. Previous research found GA exposure rates and pregnancy outcomes comparable to the general population. This study evaluates pregnancy, fetal, and infant outcomes following maternal exposure to GA 20 and 40 mg/mL to provide a cumulative four-year update.

Methods: Post-marketing pregnancy data reported between April 1, 2019 to March 31, 2023 were searched in Teva's Global Safety database and supplemented with 1- and 12-month post-delivery questionnaires. Prospective pregnancy data, collected prior to known pregnancy outcomes or congenital malformations, were used to estimate pregnancy and infant outcomes for GA 20 and 40 mg/mL exposure. Rates of major congenital malformations (MCM) and other pregnancy and infant outcomes were estimated.

Results: Among 3514 pregnancies, multiple sclerosis (MS) was the primary indication (62.4%), with most exposure to GA 40 mg/mL (72.2%), in the first trimester (94.9%). Of these, 2455 (69.9%) had known pregnancy outcomes. Of 1211 prospective pregnancies (1239 fetuses) with known outcomes, 1138 (91.8%) resulted in live births. Fetal loss occurred in 101 cases (8.2%), including spontaneous abortion (6.7%), elective termination (0.8%), ectopic pregnancy (0.3%), stillbirth (0.2%), and other (0.2%). The prevalence of MCM was 1.5% overall (95% CI, 0.9-2.4) and 1.9% during organogenesis (95% CI, 1.1-3.1), comparable to background rates. Minor congenital malformations were less frequent (0.7%). Prospective pregnancies with completed questionnaires (n = 539) reported preterm birth (9.8%), low/very low birth weight (7.3%), neonatal intensive care unit (NICU) admission (8.8%), and adverse events (17.4%). Infant growth remained within normal ranges. Of 384 women completing the 12-month questionnaire, 146 reported breastfeeding with GA (average 8 months). Among these, 14/125 (11.2%) respondents reported infant hospitalization. Growth parameters for 55 breastfed infants were within normal limits. Overall, pregnancy and infant outcomes were similar across GA doses.

Discussion: Despite limitations of post-marketing data, this four-year study found no increased risk of adverse pregnancy, fetal, or infant outcomes associated with GA exposure. The MCM rates aligned with the general population, and infant outcomes during breastfeeding were within normal ranges. These findings support the safety of both 20 and 40 mg/mL GA during pregnancy and breastfeeding.