Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis

Abstract

ObjectiveAssessing the risk of clinical and radiological reactivation during pregnancy and post partum in women with multiple sclerosis (MS) treated with natalizumab (NTZ) throughout pregnancy (LONG_EXP) compared with women interrupting treatment before (NO_EXP) and within >−30 days and ≤90 days from conception (SHORT_EXP), and describing newborns’ outcomes.MethodsMaternal clinical and radiological outcomes and obstetric and fetal outcomes were retrospectively collected and compared among groups (NO_EXP, SHORT_EXP, LONG_EXP). Predictors of clinical and radiological reactivation were investigated through univariable and multivariable analysis.Results170 eligible pregnancies from 163 women referring to 29 Italian MS centres were included. Annualised relapse rate (ARR) was significantly lower in LONG_EXP (n=66, 0.02 (0.001–0.09)) compared with NO_EXP (n=31, 0.43 (0.21–0.75), p=0.002) and SHORT_EXP (n=73, 0.46 (0.30–0.66), p=0.0004) during pregnancy, and in LONG_EXP (0.12 (0.05–0.24)) compared with SHORT_EXP (0.30 (0.17–0.50), p=0.008) during post partum. Gadolinium-enhancing (Gd+) lesions were less frequent in LONG_EXP (n=6/50, 2.00%) compared with NO_EXP (n=9/21, 42.86%) and SHORT_EXP after delivery (n=17/49, 34.69%, p=0.010).Delaying NTZ resumption after delivery significantly increased the risk of relapses (OR=1.29 (95% CI 1.07 to 1.57), p=0.009) and Gd+ lesions (OR=1.49 (95% CI 1.17 to 1.89, p=0.001). Newborns’ weight, length, head circumference and gestational age did not differ among groups after adjusting for confounders. Anaemia was tracked in 4/69 LONG_EXP newborns. Congenital anomaly rate was within the expected range for the untreated MS population.ConclusionsOur findings indicate that in women with MS treated with NTZ before conception, continuation of NTZ throughout pregnancy and its early resumption after delivery mitigate the risk of clinical and radiological reactivation. This approach has no major impact on newborns’ outcomes.

Fertility, pregnancy and childbirth in women with multiple sclerosis: a population-based study from 2018 to 2020

“…On the other hand, the presence of DMT escalation (in 11.7% and 41.5% of women with MS who were untreated or discontinued from their DMTs in the 12 months before conception, respectively) suggests relapse occurrence after delivery, or, at least, a perceived risk thereof (eg, MRI activity) 7 30–36. Overall, while we confirmed that a number of women with MS might not require DMT during pregnancy,8 in the case of active MS, safe medications should be considered to achieve disease control during pregnancy, at the time of delivery and afterwards, as recently shown in the case of natalizumab 37 38…”

Multiple Sclerosis in Pregnancy: A Commentary on Disease Modification and Symptomatic Drug Therapies

“…An important factor to consider is disease reactivation in response to natalizumab withdrawal [ 18 ] both prior or during pregnancy, which has serious implications leading to the accumulation of permanent irreversible disability [ 19 ]. More recent data add support to the approach of continuing natalizumab during pregnancy with early treatment postpartum, rather than cessation prior to or following conception, as this appears to be associated with lower clinical and radiological MS disease activity in the post-partum period [ 20 ].…”

Maternal Multiple Sclerosis and Offspring’s Cognitive and Behavioral Development: What Do We Know until Now?

“…In pregnancies exposed to natalizumab, no adverse fetal outcome emerged; however, there is the need to assess newborns’ risk of hematological alterations [ 35 , 37 ]. It is crucial to consider that the cessation of natalizumab may result in severe MS reactivation, highlighting the necessity of understanding the right time of drug discontinuation [ 37 ].…”

“…In pregnancies exposed to natalizumab, no adverse fetal outcome emerged; however, there is the need to assess newborns’ risk of hematological alterations [ 35 , 37 ]. It is crucial to consider that the cessation of natalizumab may result in severe MS reactivation, highlighting the necessity of understanding the right time of drug discontinuation [ 37 ]. To date, women with high-activity disease and a high risk of relapse are recommended to continue natalizumab until the beginning of the third trimester and then resume 8–12 weeks after delivery, possibly spacing out infusions during pregnancy [ 32 ].…”

“…On the other hand, a washout period is strictly recommended for fingolimod (2 months), ocrelizumab (12 months) and teriflunomide (2 years or a complete accelerated elimination procedure) [ 32 ]. Although the first indication is to discontinue medications during pregnancy, IFN and GA may be continued during pregnancy, as well as natalizumab, given the significant risk of disease reactivation [ 32 , 37 ]. Indeed, this medication is usually given to patients with highly active disease.…”