Late-breaking: Continuation of natalizumab or interruption during pregnancy

Pregnancy in female MS patients treated with natalizumab can expose the patients to high risk of relapses and sustained disability progression. Maintaining natalizumab, at least until conception, and re-starting treatment early after delivery was confirmed to be the optimal strategy when looking at maternal risk. The decision must take into account possible foetal risks and breastfeeding choice. The effects of different timings of natalizumab suspension before and during pregnancy were presented as late-breaking news [1].

Pregnancy is an emerging issue in MS, which influences treatment choice. Dr Doriana Landi (Tor Vergata University, Italy) started her lecture by stating It is well known that pregnancy is not compatible with all high-efficacy treatments, “especially second-line treatment, used to treat women with highly active MS. So, there is a need to accumulate data on how to manage these patients, and planning a pregnancy.”

There are several anecdotal reports and previous studies showing that suspension of natalizumab due to pregnancy is associated with dramatic disease worsening. “This is mainly due to the fact that the pharmacodynamic effects of natalizumab start to decline 8-12 weeks after the last infusion”, Dr Landi explained. Currently, wash-out of natalizumab in women with MS planning a pregnancy is discouraged due to high risk of disease reactivation. Natalizumab suspension early after the last menstrual period, whilst producing a 3-fold reduction of relapses during pregnancy, does not rule out the risks. Continuation of natalizumab is a promising strategy to minimise the occurrence of relapses during pregnancy and postpartum. However, there is a need for new evidence supporting the efficacy and safety of this strategy.

In the current analysis, women with MS treated with natalizumab and undergoing pregnancy, followed in 19 Italian MS centres, were analysed. They were divided into 3 groups according to time of last infusion of natalizumab with respect to last menstrual period:

• Group 0: before last menstrual period;
• Group 1: within the first trimester of pregnancy; and
• Group 2: continuing treatment after the first trimester [1].

A total of 92 completed pregnancies were evaluated, from 84 women with MS (mean age 31.4 years, median EDSS 2.0) and giving birth to 94 new-borns (mean gestational age 38.4 weeks, birthweight 2,878 gram, length 48.23 cm). The median interval between last dose of natalizumab and last menstrual period was -70 days for group 0, +21 days for group 1, and +189 days for group 2. Group 2 received a median of 5 natalizumab infusions during pregnancy with a median last prepartum-delivery dose interval of 81 days [1].

For women restarting natalizumab in the postpartum period, median interval between last prepartum and first postpartum dose was 411 days in group 0, 288 days in group 1, and 103 days in group 2. Annualised relapse rate (ARR) during pregnancy was median 1.06 in group 0, 0.49 in group 1, and 0.09 in group 2 (see Figure). ARR postpartum was median 0.39 in group 0, 0.23 in group 1, and 0.10 in group 2 (see Figure). ARR was lower in pregnancies exposed to natalizumab after conception and became zero in pregnancies exposed for >90 days. ARR was higher in the postpartum period in unexposed pregnancies and reliably depended on delayed treatment resumption. The mean gestational age (P=0.523), birthweight (P=0.896) and length (P=0.331) of the new-borns were not different in these 3 groups [1].

Figure. ARR before and during pregnancy and postpartum [1].



It was concluded that continuation of natalizumab beyond conception reduced the risk of relapse during pregnancy and was not associated with major foetal risks. Although this study was underpowered to detect statistically significant differences among pregnancies exposed up to the first trimester and beyond, the investigators observed that prolonging treatment protected from relapse occurrence in a time-dependent manner. Dr Landi noted that in case of treatment prolongation up to the third trimester, it is likely desirable to restart infusions within 12 weeks from the last prepartum infusion, to minimise the risk of “doubled” disease rebound. It needs to be assessed whether extended dosing is as protective as regular dosing, although no differences were seen in this cohort [1].

Foetal parameters did not vary according to different exposure to natalizumab, however, birthweight was numerically slightly lower in the 3 groups compared to general pregnancies. Anaemia was recorded only in newborns exposed beyond the first trimester, but there were confounding factors. No malformations cluster has been identified according to European Surveillance of Congenital Anomalies (EUROCAT) registry [1]. A larger sample is needed to correctly estimate the incidence of foetal complications in exposed pregnancies and provide conclusive data useful for patients counselling.

1. Landi D, et al. ECTRIMS 2019, abstract 338.

Posted on 8 November 201919 November 2021