Many disease modifying treatments for patients with relapsing form of multiple sclerosis are currently Category C, with one being Category X, which has contributed to the prevailing sentiment that MS patients should avoid becoming pregnant while taking these medications. While pregnancy avoidance is not always required, caution should be used when patients are taking the newer MS medications. For some medications, pregnancy should be avoided, and otherwise a clear plan for an appropriate wash-out period should be in place. Reproductive plans should also be discussed with male patients in some circumstances, as one of the oral medications (Aubagio) is known to pass through semen. The chart below summarizes what studies have shown regarding the safety of commonly used DMTs on perinatal and developmental outcomes in offspring of mothers with MS.
|DMT||Study Summary||FDA Category|
|Interferon beta||Amato et al. in a prospective cohort study looked at 88 pregnancies classified as exposed (avg. four weeks) and found that, regardless of different formulations and doses, exposure was not associated with an increased risk of spontaneous abortion, but was associated with both lower baby weight (though not particularly low birth weight) and length. IFN beta exposure and cesarean delivery were the only predictors of preterm delivery. In the exposed group they did not observe any significant fetal complications, malformations, or developmental abnormalities over a median follow-up of 2.1 years.1||C|
|Glatiramer Acetate||Giannini et al. examined 17 pregnancies with exposure to GA (also average exposure of four weeks) and found no increased risk of spontaneous abortion, nor higher risk of preterm or cesarean delivery, nor a lower weight and length of babies found.2||B (No adequate human studies)|
|Natalizumab||German study with 35 natalizumab-treated patients studied and exposure did not appear to be associated with shorter mean birth length, lower mean birth weight, or lower mean gestational age.3||C|
|Mitoxantrone||Animal studies and human case reports suggest potential harm and teratogenicity with no controlled human studies to date. Should be prescribed only with assurance of effective contraception. 4||D|
|Fingolimod||Drug has only recently entered the market, so no human studies exist. Animal studies have shown developmental toxicity, including teratogenicity and embryolethality during organogenesis. In rats, most frequently reported fetal visceral malformations were persistent truncus arteriosus and ventricular septal defect. Fingolimod affects the sphingosine 1-phosphate receptor, which is involved in vascular formation during embryogenesis.5||C|
|Teriflunomide||Animal studies resulted in decreased growth, eye and skin abnormalities, high incidences of fetal malformation, postnatal death, and embryofetal death at doses not associated with maternal toxicity. Has been detected in human semen, so both men and women need to use appropriate contraception. Medication can last in the system anywhere from eight months to two years after stopping treatment. If pregnancy is desired, then an elimination protocol with cholestyramine or oral activated charcoal is necessary.6||X|
|Dimethyl fumarate||Newest oral medication; animal studies have shown evidence of embryofetotoxicity, but no controlled data in human pregnancy.7||C|
|Pulse IV methylprednisolone||In a small study comparing twenty women receiving 1 g of methylprednisolone IV per month for six months postpartum to twenty-two untreated historical controls, the treated group tended to have fewer relapses in the first trimester postpartum. If patient experiences a postpartum exacerbation, treatment with IV methylprednisolone can be used, but during therapy breastfeeding should be suspended as corticosteroids pass through breast milk. High-dose corticosteroids are associated with a slight increase in thrombosis risk, which is already higher during the postpartum period, so only relapses associated with disruption of daily activities should be considered for treatment. During pregnancy, MS exacerbations can be treated by high dose IV corticosteroids as indicated/needed.8||C|
- Amato MP, Portaccio E, Ghezzi A, Hakiki B, Zipoli V, Martinelli V, et al. Pregnancy and fetal outcomes after interferon-β exposure in multiple sclerosis. Neurology. 2010 Nov 16;75(20):1794-802.
- Giannini M, Portaccio E, Ghezzi A, Hakiki B, Pastò L, Razzolini L, et al. Pregnancy and fetal outcomes after Glatiramer Acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study. BMC Neurol. 2012 Oct 22;12:124.
- Hellwig K, Haghikia A, Gold R. Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment. Mult Scler. 2011 Aug;17(8):958-63.
- Lu E, Wang BW, Guimond C, Synnes A, Sadovnick AD, Dahlgren L, et al. Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance. Expert Rev Neurother. 2013 Mar;13(3):251-60.
- GILENYA® (fingolimod) capsules Full Prescribing Information.
- AUBAGIO® (teriflunomide) Full Prescribing Information.
- TECFIDERA® (dimethyl fumarate) delayed-release capsules Full Prescribing Information.
- Crabtree-Hartman E. Sex differences in multiple sclerosis. Continuum Lifelong Learning Neurol 2010;16(5):193-210.