Pregnancy and Fetal Outcomes After Glatiramer Acetate Exposure in Patients With Multiple Sclerosis

A Prospective Observational Multicentric Study

Marta Giannini; Emilio Portaccio; Angelo Ghezzi; Bahia Hakiki; Luisa Pastò; Lorenzo Razzolini; Elisa Piscolla; Laura De Giglio; Carlo Pozzilli; Damiano Paolicelli; Maria Trojano; Maria G Marrosu; Francesco Patti; Loredana La Mantia; Gianluigi Mancardi; Claudio Solaro; Rocco Totaro; Maria R Tola; Giovanna De Luca; Alessandra Lugaresi; Lucia Moiola; Vittorio Martinelli; Giancarlo Comi; Maria P Amato

Disclosures

BMC Neurol. 2012;12(124) 

In This Article

Abstract and Introduction

Abstract

Background Only 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 methods We 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.

Results Data 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.

Conclusions Data 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.

Introduction

Since Multiple Sclerosis (MS) predominantly affects women in childbearing phase of their lifes, the issue on the tolerability and safety of disease-modifying therapy (DMT) use in pregnant relapsing-remitting (RR) MS patients has become increasingly important. This concept is especially prominent in subjects with highly active MS, in which the discontinuation of DMT in case of pregnancy planning can expose the patients to the risk of relapses. Over the past few years several studies have suggested that exposure to Interferon-β (IFNB) therapies during early pregnancy period is safe.[1–4] As for glatiramer acetate (GA) data in humans are rather limited. To date, GA is classified by US FDA as a Category B drug in relation to pregnancy, due to the absence of foetal risk in animal studies.[5] However few studies suggested the absence of adverse outcomes from GA exposure during the early pregnancy.[4,6–8] In particular, a prospective observational controlled cohort study on 31 pregnancies exposed to GA found neither drug-specific adverse pregnancy outcomes nor birth defects compared to an MS and non-MS control groups.[6] Moreover, two smaller uncontrolled studies reported a preliminary experience on continuous exposure of GA throughout the whole course of pregnancy.[9,10] Neither drug-related obstetric/neonatal complications nor malformations, were reported in the pregnancies exposed to GA. The Authors also preliminarly suggested a protective role of continuos exposure to GA during pregnancy against the risk of relapses in the post-partum period.

In a previous multicentric, prospective study we collected pregnancies followed-up in the main Italian MS centers and addressed the issue of IFNB exposure. In the same study we also gathered detailed information on pregnancies exposed to GA.[1] The objective of this further analysis was to determine the safety of in utero exposure to GA in terms of pregnancy and foetal outcomes as well as developmental abnormalities of the babies after birth.

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