Disease Evolution in Women With Highly Active MS Who Suspended Natalizumab During Pregnancy vs Rituximab/Ocrelizumab Before Conception

BACKGROUND AND OBJECTIVES: In women with highly active multiple sclerosis (MS), suspending rituximab (RTX) for planning pregnancy is associated with low disease reactivation. Whether this strategy reduces the risk of disease reactivity as compared with suspending natalizumab (NTZ) 3 months after conception is unclear. METHODS: We retrospectively included women with MS followed in our department during pregnancy and 1 year after birth who suspended NTZ at the end of the first trimester (option mostly proposed before 2016) or suspended RTX/ocrelizumab (RTX/OCR) in the year before conception (option proposed since 2016). RESULTS: In women who suspended NTZ, 45 pregnancies resulted in 3 miscarriages and 42 live births, including 1 newborn with major malformations. In women who suspended RTX/OCR, 37 pregnancies resulted in 3 miscarriages and 33 live births; 1 pregnancy was terminated for malformation. During pregnancy, relapse occurred in 3/42 (7.1%) patients of the NTZ group and 1/33 (3%) of the RTX/OCR group (p = 0.6). After delivery, relapse occurred in 9/42 (21.4%) patients of the NTZ group and 0/33 of the RTX/OCR group (p < 0.01). In the NTZ group, 8/9 relapses occurred in patients who restarted NTZ less than 4 weeks after delivery. The proportion of patients with gadolinium-enhanced and/or new T2 lesions on brain or spinal cord MRI performed after delivery was higher in the NTZ than RTX/OCR group (14/40 [35%] vs 1/31 [3%] patients, p = 0.001), the proportion with EDSS score progression during the period including pregnancy and the year after delivery was higher (7/42 [17%] vs 0/33 patients, p = 0.01), and the proportion fulfilling NEDA-3 during this period was lower (21/40 [53%] vs 30/31 [97%] patients, p < 0.001). DISCUSSION: Suspending RTX/OCR in the year before conception in women with highly active MS was associated with no disease reactivation during and after pregnancy. As previously reported, stopping NTZ at the end of the first trimester was associated with disease reactivation. In women receiving NTZ who are planning pregnancy, a bridge to RTX/OCR for pregnancy or continuing NTZ until week 34 are both reasonable clinical decisions. The RTX/OCR option is more comfortable for women and reduces the exposure of infants to monoclonal antibodies.