Despite the fact that there are no DMTs approved by the US Food and Drug Administration (FDA) for use during pregnancy, there is evolving guidance in the literature on use of disease-modifying therapies (DMTs) during pregnancy or breastfeeding. The reviews by Coyle et al. (2019), Vaughn et al. (2018), Bove et al. (2014), Cree (2013), Krysko et al. (2023), and Bove and Houtchens (2022) offer evolving guidance for clinicians who are counseling their patients about treatment options.
Oftentimes, DMTs are not required by individuals living with MS who become pregnant. The decision whether to discontinue DMT depends on the safety of the product, risk of MS reactivation in the patient/MS stability and patient preferences. Typically, to ensure no effect of DMT at the time of conception, a DMT should be stopped 5 maximal half-lives before conception (Kaisey et al., 2018). The exception is teriflunomide which has known teratogenic effects, and specific prescribing information guidance including a pregnancy registry. If discontinued, natalizumab and S1P receptor modulators such as fingolimod, can be associated with severe rebound relapses before, during and after a pregnancy (Alroughani, et al., 2018; Das et al., 2018, Smith et al., 2020). In addition, dimethyl fumarate and alemtuzumab have been shown to have unclear but likely risks and, therefore, these medications should be avoided if pregnancy is desired (Langer-Gould, 2019).
While there is not enough human data available for the FDA to support the use of injectable DMTs leading up to or during pregnancy, observational studies support the relative safety of injectable DMTs (glatiramer acetate, interferon-beta) for use in pregnancy and some clinicians will allow use of these agents up until conception (Coyle, 2016). The FDA cautions that pregnancy should be avoided during treatment with B-cell depleting therapies and for 6 months after stopping therapy.
The use of B-cell–depleting therapies during pregnancy remains understudied and definitive safety data are lacking. B-cell depleting agents are large IgG1 monoclonal antibodies, which are minimally transferred across the placenta. During the first trimester, maternal transfer of immunoglobulin is negligible. Highest exposure occurs after week 32, during fetal growth, and exposure to these therapies at this time can lead to neonatal hematological abnormalities. B-cell–depleting therapies have long lasting effects and have the potential to reduce the risk of inflammatory activity during pregnancy despite treatment discontinuation prior to conception. Therefore, some clinicians will allow use of these agents up until conception.
Counseling on the risks of stopping a DMT (i.e. potential for disease activity) or continuing it during pregnancy (i.e. potential for fetal harm) should be personalized and include FDA guidance and real-world data. (Galati et al., 2022).
Relapse management during pregnancy
Relapses severe enough to warrant treatment can be safely managed with a short course of corticosteroids after the first trimester. Plasma exchange for severe relapses may also be safe during pregnancy, though data are limited (Coyle et al., 2019). Methylprednisolone is the preferred drug because it is metabolized before crossing the placenta (Coyle, 2016; Bove et al., 2014; Ferrero et al., 2004).