Multiple Sclerosis Disease Activity and Disability Following Discontinuation of Natalizumab for Pregnancy

Abstract

Key Points Question Is early natalizumab cessation before or during the first trimester of pregnancy associated with multiple sclerosis relapse occurrence and relapse-related disability? Findings In this cohort study of 274 pregnancies, relapses during pregnancy and postpartum were common, with more than 10% of women retaining clinically meaningful disability from pregnancy-related natalizumab cessation relapses 1 year after delivery. Neither pregnancy itself, restarting natalizumab shortly after delivery, nor exclusive breastfeeding was associated with protection against these relapses. Meaning These findings suggest that women with multiple sclerosis need to be informed about the risks of early natalizumab cessation due to pregnancy or planned pregnancy, and treatment alternatives should be considered.

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

“…Minimising the risk of relapses due to NTZ cessation is of utmost relevance,9 as our study confirms that relapses during pregnancy and postpartum may lead to EDSS worsening and permanent disability accrual.…”

“…While presenting a high efficacy, NTZ’s protection against disease reactivation starts to decline from the eighth week after the last infusion due to its pharmacokinetics 5. Women who interrupt NTZ for maternity planning encounter an increased risk of relapses before or during pregnancy due to the rapid immune reconstitution after treatment interruption,6–9 which is unmitigated by pregnancy-induced immunomodulation.…”

Peripartum disease activity in moderately and severely disabled women with multiple sclerosis

“…We confirmed an association between natalizumab and fingolimod cessation and peripartum relapses, which was expected based on prior observations of rebound disease activity after cessation of these DMTs. [18][19][20] The lack of observed reduction in relapses or MRI activity after early DMT re-initiation postpartum should be interpreted with caution given the paucity of MRI data available and the heterogeneity in treatment strategies across multiple centers over a relatively long time period (2000-2021). We also did not have access to information regarding DMT adherence.…”

“…Cessation of natalizumab or fingolimod can lead to rebound relapses within several months, and recent studies have suggested that pregnancy does not protect against this risk. 18 – 20 We, therefore, evaluated intra- and postpartum relapse activity in pregnancies where natalizumab or fingolimod was stopped between 3 months preconception and the end of the first trimester of pregnancy, termed “periconception natalizumab cessation” (PNC) and “periconception fingolimod cessation” (PFC).…”

Ocrelizumab during pregnancy and lactation: Rationale and design of the MINORE and SOPRANINO studies in women with MS and their infants

“…Not only does this subject women to periods where they are not treated for their MS, but discontinuation of some treatments before pregnancy (e.g. S1P receptor modulators and natalizumab) can further increase relapse risk (Meinl et al, 2018;Novi et al 2017;Alroughani et al 2018;Langer-Gould et al 2019;Yeh et al 2021;Hellwig et al 2022) and long-term disability (Portaccio et al 2021).…”