Glatiramer Acetate for MS Appears Safe Throughout Pregnancy

Deborah Brauser

November 09, 2017

PARIS — Use of branded glatiramer acetate (GA; Copaxone, Teva) throughout pregnancy is relatively safe for women with multiple sclerosis (MS) and their offspring, new research suggests.

A cohort study of 216 women who chose, after consultation with their physicians, to continue treatment with GA throughout pregnancy showed that the rate of congenital disorders in the newborns was not significantly different from that in a comparison general US population database (3.2% vs 2.8%, respectively).

The number of observed cases of congenital disorders (n = 7) was also similar to that seen in EUROCAT, a European network of population-based registries (n = 5.4).

In addition, 86% of the babies were born at full term, defined as at least 37 weeks. Of those who were preterm, 89% were born between weeks 34 and 36 and were considered to be "late preterm." While the distribution of birth weight was similar between the treatment group and the US population, very low birth weight, defined as less than 1.5 kg, was not reported.

As for adverse events (AEs) during the neonatal period, there were three cases of neonatal respiratory distress/apnea and two cases each of neonatal jaundice and hypoglycemia.

Orit Neudorfer, MD, Teva Pharmaceutical Industries, Petach Tikva, Israel, said that this is the largest cohort with full pregnancy exposure to GA "for which data has been published."

"We think the data are very reassuring. It seems in this cohort there are no adverse effects from Copaxone," Dr Neudorfer told Medscape Medical News.

She presented the findings here at the 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.

Asked for comment, Mar Tintore, MD, PhD, Department of Neurology-Neuroimmunology and the MS Center of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain, noted that these results, along with information from past experimental models, "indicate that this treatment is pretty safe."

"This takes away the obligation of having to stop treatment in pregnancy," added Dr Tintore.

Many Questions

Pregnancy has been shown to be almost protective for mothers with MS, but questions remain about possible effects from disease-modifying therapies (DMTs) to moms and fetuses.

"DMTs for MS are often discontinued for women who intend to become or are confirmed pregnant," write the investigators. But for those with severe or highly active MS, "the benefit of treatment…may outweigh the unknown risk to the fetus from DMTs," they add.

"Although DMTs are not recommended for use in pregnancy, it is not uncommon for women treated with GA to be exposed before the pregnancy is determined, or even throughout pregnancy."

Past analyses of 20 years' worth of records in Teva's database showed that among more than 8000 pregnancies, there was "no increase in risks for malformative or fetal/neonatal toxicity or pregnancy loss" in those who were exposed to branded GA, report the researchers. However, treatment exposure was mostly limited to the first trimester. 

For the current study, the investigators wanted to assess pregnancy outcomes in women with MS who were exposed to the drug during all three trimesters. They examined 216 of such cases in the manufacturer's pharmacovigilance database.

The average age for these women was 32 years, and all cases of pregnancy resulted in a live birth. In addition, 69% of the cases were in the United States; 13% in Brazil; 3.7% in Germany; 2.3% each in Canada and Turkey; and 1.4% or less in France, Israel, Portugal, Spain, Japan, Mexico, and the Netherlands.

In addition, rates of congenital disorders were compared with reference rates from 2010 to 2014 in EUROCAT and rates from the US population–based Metropolitan Atlanta Congenital Defects Program (MACDP) from 1978 to 2005.

The standardized incidence ratio of GA-associated congenital disorders was 1.29 (95% confidence interval, 0.52 - 2.66) compared with EUROCAT data, which was not statistically different.

"Safe Option"

In the 180 newborns of GA-treated mothers that had information on gestational age, 85.6% reached full gestation of at least 37 weeks vs 90.4% of the US general population group; 14.4% vs 9.6%, respectively, were born at less than 37 weeks.

While 88.5% of the preterm GA-exposed babies were born between weeks 34 and 36, 7.7% were born at 32 to 33 weeks and 3.9% were born at 28 to 31 weeks.

Birth weight data, which were known for 116 of the GA-exposed newborns, showed that 89.7% had a normal birth weight vs 90.6% of the general population group. In addition, 10.3% vs 8.1%, respectively, had low birth weight (defined as 1.5 to 2.5 kg) and 0% vs 1.4% had very low birth weight. 

In the treatment group, the most common AEs during pregnancy "were those associated with MS symptoms and classical reactions to GA" (n = 16), report the researchers. There were also 4 cases of placental conditions and 3 cases each of prolonged rupture of membranes and hypertension/preeclampsia.

During labor and delivery, the most common complication was caesarean delivery, with 61 emergency cases and 10 elective cases. Still, this 33% rate was similar to the rate found in the US population group (32%). There were also 3 cases of increased blood loss during labor.

There were 19 reports of neonatal AEs, including 12 "single occurrences of various common neonatal conditions, with no specific trend observed." There were also two non–prematurity-related prolonged hospitalizations: one for neonatal apnea and one for neonatal withdrawal syndrome.

"The current analysis further deepens the understanding of GA's safety profile and provides further insight into potential impact of…exposure throughout pregnancy," write the investigators.

"While thorough risk-benefit assessments are required to decide whether to continue DMT treatment in women who intend to become or are confirmed pregnant, these findings do not indicate a risk of malformative or fetal toxicity with branded GA exposure throughout pregnancy," they add.

On the basis of the findings, Dr Neudorfer noted that "if there's a need for continued treatment," especially to hold back a relapse during pregnancy or postpartum, "this option is safe."

Helpful for Clinical Practice

Dr Tintore agreed that GA may be a relatively safe option for some active patients, "but many of these patients during pregnancy are not very active" because pregnancy is often associated with a decrease in risk for attacks.

"So in the majority of patients, you do not need to maintain this treatment during pregnancy," she told Medscape Medical News. Still, "GA is a good option when you have a young woman who has a mild disease and she wants to be treated, but at the same time she's thinking of getting pregnant," said Dr Tintore.

"Many women will stop treatment once they become aware of being pregnant," but with GA they don't have to worry that treatment before they were aware will cause problems later on, she added.

She noted that she and her colleagues previously were advising patients to stop DMTs before trying to become pregnant. That was a problem because pregnancy could take several months or longer, which meant the patient was going months or longer without treatment.

"Now, that is not the case. I think the most important thing about this [drug] is not so much keeping the treatment throughout pregnancy but maintaining the treatment while trying to get pregnant. That's a great help for our daily practice."

The study was funded by Teva, and Dr Neudorfer is an employee of Teva.

7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017. Poster Session 1, abstract 765. Presented October 26, 2017.

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