Estimating Risk of Multiple Sclerosis Disease Reactivation in Pregnancy and Postpartum: The VIPRiMS Score

Abstract

Background:Evidence guiding personalized decision-making with respect to disease-modifying therapy (DMT) around pregnancy in relapsing multiple sclerosis (RMS) is lacking.Objective:To generate and validate a risk score for disease reactivation intrapartum and postpartum in RMS.Methods:From the Vienna Innsbruck MS database (VIMSD), we included 343 pregnancies in patients with RMS. Primary endpoint was disease reactivation. Patients were randomly assigned 2:1 in a generation and validation dataset. A predictive score was calculated using the Cox regression and validated.Results:In the generation dataset, occurrence of relapse and type of DMT in the year before conception, DMT washout duration, the Expanded Disability Status Scale (EDSS) at conception, and time until DMT restart postpartum were identified as independent predictors of disease reactivation (p < 0.001). The resulting 10-point risk score robustly predicted reactivation (explaining 75% of variance, p < 0.001) identifying patients at high [≥6 points; mean risk 65%; range 50–100%; hazard ratio (HR) 14.5], intermediate (3–5 points; mean risk 24%; range 15–35%; HR 4.3), and low risk (≤2 points; mean risk 6%; range 0–8%) of disease reactivation in pregnancy and up to 6 months postpartum.Conclusion:The composite Vienna Innsbruck Pregnancy Risk in Multiple Sclerosis (VIPRiMS) score is a valuable clinical tool to support patients and neurologists in anticipating risk and, thus, individualizing treatment decision-making around pregnancy.

Sex impacts treatment decisions in multiple sclerosis

“…Although continuous administration of CD20 antibodies is necessary to suppress disease activity, no excessive disease activity after discontinuation has been observed so far [ 34 ]. In contrast to hDMT, discontinuation of mDMT in women with a stable course of disease without clinical or radiological disease activity is considered relatively safe [ 35 ].…”

Disease-Modifying Therapies (DMTs) in Pregnant and Lactating Women with Multiple Sclerosis: Analysis of Real-World Data from EudraVigilance Database

“…The ICSRs related to pregnancy/breastfeeding complications were mostly associated with the "pregnancy" condition both in the mother and the baby compared to the "breastfeeding" condition. This could be due to the possibility for the mother to choose between natural and artificial lactation, based on the need to restart DMT therapy immediately or postpone it to avoid potential damage to the baby [41]. In a cohort of approximately one million pregnant women identified using a wide US healthcare and pharmacy database, MacDonald et al selected 1649 women with MS of whom 35% were exposed to DMTs during pregnancy.…”

Assisted Reproductive Techniques in Multiple Sclerosis: Recommendations from an Expert Panel

“…Notably, the DMT should be assessed, especially if a switch of DMT, or a washout period, is necessary before conception. Current recommendations from regulatory agencies include avoiding pregnancy during treatment and, depending on the DMT, maintaining a 2-to 6-month washout period before conception [25][26][27]. Finally, in women with MS, an evaluation of cervical pathologies through cytology tests should be undertaken since some DMT, in particular those with an immunosuppressing mechanism, such as mitoxantrone, azathioprine and alemtuzumab, have been associated with a potential risk of cervical dysplasia (Table 1) [28,29].…”