New Data on Natalizumab During
Pregnancy in MS

September 19, 2019

New data on the use of natalizumab (Tysabri, Biogen) during pregnancy in women with multiple sclerosis (MS) have shown that continued use of the drug is associated with a lower risk of relapses during pregnancy and during the postpartum period.

In terms of possible effects on infants, results showed continued use of natalizumab into later pregnancy was associated with an increased risk of anemia. There was also a higher frequency of birth defects in the infants born to women who continued on the drug compared with those that stopped before becoming pregnant, but the majority of these occurred in a child who was a twin.

The researchers concluded that confounding factors needed to be taken into account and the sample size in this study was too small to estimate the effect of the drug on risk of birth defects.

These data come from a new Italian observational study presented at last week's 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019.

Presenting the study, Doriana Landi, MD, University of Rome Tor Vergata, Italy, concluded: "We have observed that prolonging natalizumab treatment in pregnancy protects from MS relapse occurrence in a time-dependent fashion."

"It is desirable to resume infusions within 12 weeks from the last prepartum infusion to minimize the risk of disease rebound," she added.

"Larger samples sizes are required to estimate the incidence of fetal complications in exposed pregnancies and provide conclusive data for patient counseling."

ECTRIMS vice-president and study coauthor Maria Pia Amato, MD, University of Florence, Italy, explained to Medscape Medical News that women on highly active drugs like natalizumab who discontinue treatment before pregnancy can have severe reactivation of disease, "and this is of course a very bad situation during pregnancy."

"We found in a previous Italian study that those who discontinued natalizumab after conception (at the time of the first positive pregnancy test) did better than those that stopped before getting pregnant," Amato said.

In the current study, the researchers looked at a cohort of 89 women who continued natalizumab for different durations of the pregnancy.  

The women were divided into three groups: those who discontinued before pregnancy (group 0; n = 31); those who discontinued in the first trimester of pregnancy (group 1; n = 30); and those who continued taking natalizumab into the second and third trimesters (group 2; n = 28).

In group 0, natalizumab was discontinued a median of 70 days before the last menstrual period. The drug was continued for a median of 21 days after the last menstrual period in group 1 and for 197 days in group 2.

Women in group 2 received a median of five natalizumab infusions during pregnancy, with the last dose given a median of 81 days before delivery. The majority of women in group 2 continued taking the drug until the 28th week of gestation.

For women restarting natalizumab after delivery, the median interval between last prepartum dose and first postpartum dose was 411 days in group 0, 288 days in group 1, and 103 days in group 2.

Annualized relapse rate during pregnancy was 1.06 in group 0; 0.49 in group 1; and 0.09 in group 2.

The annualized relapse rate postpartum was 0.39 in group 0, 0.23 in group 1, and 0.10 in group 2.

As for the infants, there was no difference in mean gestational age, birthweight, and length between the 3 groups.

Anemia was found in five infants in group 2, although three were premature and an interaction with prematurity cannot be excluded, Landi reported.  

Malformations occurred in one newborn (minor defect) in group 0; 4 newborns in group 1 (1 major and 4 minor defects) and 4 newborns in group 2 (4 major and 2 minor). "But in group 2 the majority of defects occurred in one twin so this may not be applicable to the wider population," Landi said.

"The longer the exposure of the mother to natalizumab therapy the better her MS outcome," Amato commented. "This included fewer relapses during pregnancy and also during the postpartum period — especially if the drug was resumed within 12 weeks — that is its duration of action.  

"We have to look at the balance between risk to the mother and risks to the baby. While it seems that natalizumab is reasonably safe for the baby, we did see a few cases of anemia in those born to women who continued to receive the drug later in pregnancy," Amato noted. 

"We believe the optimal strategy to reduce risk for the mother — to reduce MS relapses and relapse-associated disability — is to continue the drug until maybe 30 weeks," she added.

Amato explained that this was an observational study, with each patient making her own decision in collaboration with her doctor on whether to stop or continue treatment during pregnancy, how long to continue, and whether to extend the dosing interval. Natalizumab is usually given once every 4 weeks. The interval of dosing was extended in some women to every 6 or 7 weeks.

"In my clinical practice I would discuss what is known and what isn't known with each woman of course. That is fundamental," Amato concluded. "My advice would be to continue treatment, as these are by definition highly active patients with a high risk of relapse if they stop taking the drug. I would recommend they continue until at least the end of the second trimester during pregnancy, as in the third trimester you can have some hematological abnormalities."

Commenting for Medscape Medical News, session co-chair Tobias Derfuss, MD, University Hospital of Basel, Switzerland, called this is a very important study.

"When natalizumab treatment is stopped, disease recurrence is high, and it is hard to treat relapses as the patient is pregnant, so we have limited options," he said. "It is very important to get information on the safety of natalizumab in pregnancy."

Derfuss said this issue is also being investigated at his center. "We are looking at keeping patients on treatment but extending the dosing to every 6 or 7 weeks during pregnancy and then resuming back to every 4 weeks after delivery. So far we have had good experience and certainly less disease activity — similar to what has been shown in this study," he noted.

Landi has received travel funding from Biogen, Merck Serono, Sanofi Genzyme, and Teva; honoraria for speaking from Sanofi Genzyme and Teva; and consultation fees from Merck Serono and Teva. Amato has served on scientific advisory boards for, and has received speaker honoraria and research support from, Biogen Idec, Merck Serono, Bayer Schering Pharma, and sanofi-aventis.

35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019: Abstract 338. Presented September 13, 2019.

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