Impact of disease-modifying therapies on pregnancy outcomes in multiple sclerosis: a prospective cohort study from the German multiple sclerosis and pregnancy registry.

Abstract

In recent decades, relapsing remitting multiple sclerosis (MS) became more treatable through new disease-modifying therapies (DMTs). Identifying safe treatments with minimal fetal risks for family planning is needed. In this prospective cohort from the German MS and Pregnancy Registry (DMSKW), we analyzed pregnancy and neonatal outcomes in MS-patients using descriptive statistics and logistic/linear regression models to compare DMT-exposed pregnancies to DMT-unexposed pregnancies. In 2885 DMT-exposed and 837 DMT-unexposed pregnancies, exposure was not associated with spontaneous abortions, preterm births or major congenital anomalies (MCAs). Severe infections were rare, but more frequent in the Fumarates-group (11/395: 2.8% vs. 8/837 unexposed-group: 1.0%, p-value: 0.03). Antibiotic-use was associated with 2nd-trimester (OR: 2.47, CI: 1.47, 4.05, p-value: <0.001), 3rd-trimester Natalizumab-exposure (OR: 1.75, CI: 1.15, 2.63, p-value: 0.01), and anti-CD20-exposure (OR: 2.16, CI: 1.41, 3.29, p-value: <0.001). Birthweight was significantly reduced in the Sphingosine-1-phosphate-group (β: -132 g, CI: -205, -60, p-value: <0.001), and 3rd-trimester Natalizumab-subgroup (β: -74 g, CI: -138, -9.4, p-value: 0.02). Small for gestational age (SGA) neonates were common in the Sphingosine-1-phospate- (OR: 1.65, CI: 1.07, 2.50, p-value: 0.02) and anti-CD20-group (OR: 1.54, CI: 1.01, 2.32, p-value: 0.04), and also the entire cohort (651/3459: 18.8%), exceeding the general German population rate (10%) (p-value: <0.001). We observed an increased SGA risk, especially following highly-effective DMTs, although the pathomechanisms remain unclear. More research is needed on infection risks and MCAs, perhaps by linking different registries. The DMSKW is partly supported by Almirall, Biogen, Hexal, Merck, Novartis, Roche, Sanofi Genzyme, Teva Pharma and Viatris.