Family Planning for People with Multiple Sclerosis in Saudi Arabia: an Expert Consensus

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
Alemtuzumab^a	(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 tablets^a	(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/siponimod^a	(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 [35–37].
Natalizumab^a	(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].
Ocrelizumab^a	(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]).