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. 2021 Feb 15;2021:6667006. doi: 10.1155/2021/6667006

Table 2.

Summary of evidence relating to the foetal safety of DMDs used for relapsing-remitting multiple sclerosis.

DMD Overview of evidence relating to safety during pregnancy
Alemtuzumaba (i) No apparent increase in the frequency of spontaneous abortions between women who had received alemtuzumab and women in the general population (2017, based on 248 pregnancies) [27].

Cladribine tabletsa (i) Similar proportions of live births and spontaneous abortion in women who received cladribine tablets or placebo during the clinical development of this DMD (2017, based on 64 pregnancies) [28].

Dimethyl fumarate (i) No signal for adverse pregnancy outcomes in 63 women in clinical trials and 125 pregnancies described postmarketing (2015) [29].
(ii) International Registry data (194 pregnancies) showed unremarkable rates of pregnancy loss and birth defects (2019) [30].

Fingolimod/siponimoda (i) Prospective Multinational Gilenya® Pregnancy Exposure Registry found a rate of birth defects consistent with the range found in the general population (based on 1,586 pregnancies, 2019) [31].
(ii) A review by the EMA found a 2-fold increase in the rate of birth malformations (2019) [32].

Glatiramer acetate (GA) (i) Registry data suggest no teratogenic effect (based on 246 pregnancies, 151 with exposure in the 1st trimester, 3 to the 3rd trimester, 95 unexposed controls, 2016) [33].
(ii) Comparison of a database including 5,042 pregnancies exposed to GA with control databases including 29% of the European births (>1.7 million/year) and >50,000 births in the USA showed no excess birth defects or other adverse pregnancy outcomes (2018) [34].

Interferon beta (INFβ) (i) 2,148 exposed and 2,025 unexposed pregnancies from the German Multiple Sclerosis and Pregnancy Registry (2016), the Merck Serono Global Drug Safety Database (2011), and a Nordic Pregnancy Registry (2018) showed no excess risk to the foetus resulting from exposure o INFβ (live births, spontaneous abortions, congenital abnormalities, and birth length/weight) relative to the general population [3537].

Natalizumaba (i) Registry data included 101 women with RRMS foetal exposure to natalizumab, 78 women with RRMS and pregnancy unexposed to natalizumab, and 97 control; non-MS pregnancies demonstrated no significant differences for major malformations, low birth weight (<2500 g), or premature birth (2015) [38].
(ii) Observational data suggested odds ratio of 3.9 for spontaneous abortion with natalizumab vs. INFβ or no treatment (p<0.001); the frequency of spontaneous abortion (17.4%) and of major congenital abnormalities (3.7%) was within estimates for the local general population (92 exposed pregnancies 2018) [39].
(iii) No excess risk of miscarriages or birth defects global Tysabri Pregnancy Exposure Registry (376 pregnancies, 2016) [40].

Ocrelizumaba (i) No signal for increased rates of spontaneous abortion in for 267 pregnancies (118 with documented foetal exposure). No foetal abnormalities were reported for 26 live births from these women (2019) [41].

Teriflunomide (i) Spontaneous abortion rate of 18.6% from 70 pregnancies with known exposure to teriflunomide; this was described as within the expected range for the general population (2019) [42].
(ii) Spontaneous abortion rate of 21% from 431 exposed pregnancies, and 4 birth defects (these were considered consistent with the rate in the general population (2019) [43].
(iii) 587 pregnancies exposed to leflunomide (for arthritis) did not suggest teratogenic potential (7% birth defects; 2019) [44].

Dates are years of publication or presentation at an international meeting. EMA: European Medicines Agency. RRMS: relapsing-remitting multiple sclerosis. aUsually considered a high-efficacy disease-modifying drug (DMD) for the management of RRMS (see reference [19]).