Disease Activity in Pregnant and Postpartum Women with Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies

Abstract

Background and ObjectivesWomen with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.MethodsWe performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued ≥28 weeks of gestation, restarted ≤1 month postpartum) or conservative (NAT-C; continued ≤4 weeks of gestation, restarted >1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods.ResultsA total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1) experienced 1 relapse in the postpartum period (ARR 0.09 95% CI 0.02-0.27). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 0.01-0.15) and 4 (4.9%) relapsed during postpartum (0.10 0.03-0.26). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 0.20-0.51) and 25 (30.5%) relapsed during postpartum (0.74 0.50-1.06). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 0.10-0.14), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 0.38-0.48). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 0.06-0.20) and 25 (15.2%) of 164 relapsing postpartum (0.39 0.26-0.57). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse.DiscussionWomen treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family.Classification of EvidenceThis study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued ≥28 weeks of gestation and restarted ≤1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies. © 2024 American Academy of Neurology.