Glatiramer acetate exposure in pregnancy: preliminary safety and birth outcomes

Abstract

With the increasing incidence of multiple sclerosis (MS) in women and the earlier use of disease modifying therapy (DMT), issues surrounding DMT and pregnancy are a regular subject of discussion with regards to optimal management. Current recommendations are to withdraw DMT prior to conception, leaving patients exposed to an uncertain period of untreated disease. The objective of this study is to report preliminary experience on glatiramer acetate (GA) exposure through conception, pregnancy and the post-partum period in a series of 13 patients with previously highly active relapsing-remitting MS. This is a prospective observational case series. Fourteen pregnancies of 13 women resulted in 13 live births (one twin pregnancy), nine exposed to GA throughout pregnancy. There were no birth defects and treatment was well tolerated. No relapses occurred during pregnancy in those continuing on treatment. In conclusion, our early experience suggests that when considering the risks and benefits of treatment withdrawal prior to pregnancy, it may be reasonable to continue GA in those patients with previously highly active disease. Consideration should also be given to the initiation of a birth register, similar to such initiatives in epilepsy, to generate more robust safety data in this controversial area.

Some Unique Considerations in Treatment of Multiple Sclerosis

“…Compared to general population, offspring of women with MS have a 20-50 times greater risk of developing MS, although the absolute risk is relatively low 4,5 . Glatiramer acetate (FDA pregnancy category B) does not appear to be associated with teratogenic risk or a higher risk of miscarriage 6 . Fingolimod is classified as FDA category C (i.e., animal studies warrant patients be counselled on foetal risk and appropriate contraception use for at least 2 months after stopping the drug).…”

“…Fingolimod is classified as FDA category C (i.e., animal studies warrant patients be counselled on foetal risk and appropriate contraception use for at least 2 months after stopping the drug). Natalizumab is also FDA category C based on the lack of human data 6 . Mitoxantrone and teriflunomide are associated with teratogenic effects and should only be prescribed to women who are using reliable contraception 7,8 .…”

Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance

“…IFN-β exposure was not associated with low birthweight (<2500 g), cesarean delivery, congenital anomaly or spontaneous abortion [12]. Fewer studies (with limited sample size) were available regarding the safety of GA [13][14][15][16] or natalizumab [17]. Therefore, while GA exposure was not associated with lower mean birthweight, congenital anomaly, preterm birth or spontaneous abortion [13], and natalizumab did not appear to increase the risk of shorter birth length, lower birthweight or lower gestational age [17], conclusive statements surrounding safety cannot be made.…”

“…For example, when classifying DMD exposure, some defined in utero DMD exposure as within 1 month prior to conception, whereas others used the estimated time of conception. All these issues outlined here could contribute to the differences in reported findings between studies -with some studies reporting harm [12,13,[25][26][27] and others not [14][15][16][17][27][28][29][30][31][32][33]. Some of the best available studies are prospective, which, by their nature, minimize reporting and recall bias (a common challenge in pregnancy-related pharmacovigilance studies).…”

“…Of these, two had relatively large sample sizes (n = 69 [13] and 88 [12]), which also allowed for adjustment of important confounders (including gestational age, parity, socioeconomic status and smoking or alcohol use) to better estimate the true effect of IFN-β exposure. In addition, some studies investigated DMD exposure late in pregnancy; three small studies (n = 9 [14], 11 [16] and 12 [15] pregnancies) reported on GA exposure up to the third trimester of pregnancy, whereas others followed long-term developmental outcomes beyond the immediate perinatal period in offspring exposed to GA [16] or IFN-β [12,26] in utero. Individual studies have also investigated maternal natalizumab exposure during pregnancy [17] and paternal DMD use around conception [28] -both represent the first cohort studies published on these topics.…”