Efficacy and Safety of Multidisciplinary Sandwich Regimen in
AQP4
‐
IgG
+
NMOSD
With Preconceptio
Li Xiao, Gengxin Lu, Qian Gao, Feiyan Wan, Zhenze Lu, Wei Qiu, Chengfang Xu, Yaxin Lu, Lejia Xu, Tingting Xia, Jiajing Chao, Yu Fu, Zhuanggui Chen, Rui Li, Yanyu Chang, Yuge Wang, Bing Qin, Yaqing Shu ABSTRACT
Background
Neuromyelitis optica spectrum disorder (NMOSD) predominantly affects women of childbearing age, accompanied by markedly elevated relapse risks during pregnancy and postpartum periods, bringing great challenges to perigravid management. At present, there is no standardized gestational therapeutic regimen for NMOSD worldwide, and data on perigravid application of B‐cell depleting agents including rituximab and inebilizumab remain limited. For patients exposed to B‐cell depleting agents before conception, balancing disease control and fetal safety is an urgent clinical problem to be solved.
Objective
This multicenter prospective cohort study aimed to evaluate the efficacy and safety of a three‐stage multidisciplinary “sandwich” management regimen in AQP4‐IgG‐positive pregnant women with NMOSD exposed to B‐cell depleting agents before conception. Maternal disease activity, pregnancy outcomes, neonatal conditions, and offspring growth and developmental characteristics within the first year of life were analyzed.
Methods
A total of 8 AQP4‐IgG‐positive pregnant women with NMOSD who received B‐cell depleting agents within 9 months prior to conception were enrolled from multiple centers between January 2022 and October 2024, including 3 patients treated with inebilizumab and 5 patients treated with rituximab. All subjects received a unified three‐stage intervention: B‐cell depleting agents were discontinued upon confirmed pregnancy; low‐dose azathioprine combined with low‐dose glucocorticoids was administered during gestation; B‐cell depleting agents were reinitiated at 2 weeks postpartum. Multidisciplinary teams consisting of neurology, obstetrics, clinical pharmacy, and neonatology departments conducted full‐cycle monitoring and follow‐up. Primary observation indicators included maternal relapse events, Expanded Disability Status Scale (EDSS) scores, B‐cell counts, gestational complications, gestational age at delivery, neonatal physical indicators, Apgar scores, congenital malformations, as well as offspring growth and neurodevelopment and vaccination safety from birth to 1 year of age.
Results
All subjects achieved term live births without severe obstetric complications. Seven patients remained relapse‐free throughout pregnancy and postpartum period with stable or improved EDSS scores; one patient discontinued all medications during gestation and suffered a relapse at 1 month postpartum. Neonatal physical indicators and Apgar scores were generally normal, one neonate presented mild hypospadias and two developed transient neonatal abnormalities; neonatal B‐cell counts at birth and 1 month of age were within normal ranges. One‐year follow‐up showed normal physical and neurodevelopment in all offspring with safe vaccination procedures.
Conclusions
For AQP4‐IgG‐positive pregnant women with NMOSD exposed to B‐cell depleting agents before conception, the multidisciplinary “sandwich” regimen featuring B‐cell depletion before conception and postpartum plus gestational bridging therapy with low‐dose azathioprine combined with glucocorticoids is safe and effective, reduces disease relapse risk and yields favorable overall maternal and fetal outcomes. This regimen may serve as a promising perigravid management strategy that warrants further validation in larger cohorts.