Pregnancy and fetal outcomes after Glatiramer Acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study

Abstract

BackgroundOnly few studies have assessed safety of in utero exposure to glatiramer acetate (GA). Following a previous study assessing the safety of interferon beta (IFNB) pregnancy exposure in multiple sclerosis (MS), we aimed to assess pregnancy and fetal outcomes after in utero exposure to GA, using the same dataset, with a specific focus on the risk of spontaneous abortion.Materials and methodsWe recruited MS patients, prospectively followed-up in 21 Italian MS Centres, for whom a pregnancy was recorded in the period 2002–2008. Patients were divided into 2 groups: drug-exposed pregnancies (EP: suspension of the drug less than 4 weeks from conception); non-exposed pregnancies (NEP: suspension of the drug at least 4 weeks from conception or never treated pregnancies). All the patients were administered a structured interview which gathered detailed information on pregnancy course and outcomes, as well as on possible confounders. Multivariate logistic and linear models were used for treatment comparisons.ResultsData on 423 pregnancies were collected, 17 were classified as EP to GA, 88 as EP to IFNB, 318 as NEP. Pregnancies resulted in 16 live births in the GA EP, 75 live births in the IFNB EP, 295 live births in the NEP. GA exposure was not significantly associated with an increased risk of spontaneous abortion (OR = 0.44;95% CI 0.044-4.51;p = 0.49). Mean birth weight and length were not significantly different in pregnancies exposed to GA than in non exposed pregnancies (p = 0.751). The frequency of preterm delivery, observed in 4 subjects exposed to GA (25% of full term deliveries), was not significantly higher in pregnancies exposed to GA than in those non exposed (p > 0.735). These findings were confirmed in the multivariate analysis. There were neither major complications nor malformations after GA exposure.ConclusionsData in our cohort show that mother’s GA exposure is not associated with a higher frequency of spontaneous abortion, neither other negative pregnancy and fetal outcomes. Our findings point to the safety of in utero GA exposure and can support neurologists in the therapeutic counselling of MS women planning a pregnancy.

The heritage of glatiramer acetate and its use in multiple sclerosis

“…Considering the choice among first-line therapies, GA offers an obvious advantage in young, potentially fertile women for the favourable safety profile in this population, as discussed above [107]. Patients with CIS are also expected to benefit from GA, given the evidence of efficacy in such patients, supported by extension studies showing clear protection from brain atrophy [86,87].…”

“…An Italian retrospective study showed that the mother's exposure to GA when the drug was suspended within 4 weeks from conception was not associated with an increased frequency of spontaneous abortion nor with other negative pregnancy and foetal outcomes compared with women in whom the medication was suspended 4 weeks or more from conception, or who were untreated [107]. These findings confirm those of a previous observational study [106] suggesting that GA and the IFNs do not represent a significant risk for prenatal developmental toxicity.…”

“…Animal reproduction studies have failed to demonstrate a risk of GA treatment to the foetus, and post-marketing studies support the absence of foetal toxicity [103][104][105][106][107][108]. For these reasons GA has been classified as FDA Class B during pregnancy [109].…”

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

“…Pregnancy loss not observed (n = 31 [13], n = 46 [61] and n = 17 [62]) Decreased fetal growth not observed (n = 31 [13] and n = 17 [62]) Teratogenicity not observed (n = 31 [13], n = 46 [61] and n = 17 [62]) Impaired development of the newborn not observed (n = 11 [16] Recommend discontinuation prior to conception or once pregnancy is known [7,8] with some suggesting a washout period of at least 1 month prior to conception [60] for women with mild MS Use until conception or into pregnancy may be recommended for women with severe or highly active MS [6] Use not recommended in breastfeeding [6] Natalizumab Contraception required for women with childbearing potential; recommend discontinuation at least 3 months prior to conception [6] Use not recommended in breastfeeding [6,11] MS: Multiple sclerosis.…”

Is it correct for a woman with multiple sclerosis to forgo medication because she may become pregnant?

“…Although safety data on exposure for newer drugs like natalizumab and fingolimod are still lacking 9 , there seems to be strong data on the safety of glatiramer acetate 10,11 and interferon beta 11,12 exposure during pregnancy. Is it time to rethink our recommendations?…”