利妥昔单抗治疗儿童重症肌无力的效果及安全性

Efficacy and safety of rituximab in the treatment of pediatric myasthenia gravis

目的评价利妥昔单抗对儿童重症肌无力(MG)的疗效和安全性。方法病例系列研究,回顾性收集2013年6月至2023年6月北京大学第一医院儿童医学中心就诊的27例应用利妥昔单抗治疗的MG患儿病例资料,分析临床表现、实验室检查、治疗方案及转归资料。结果27例患儿中男5例、女22例,起病年龄为2.1(1.6,4.8)岁,范围为8月龄至11岁,临床分型包括20例(74%)眼肌型和7例(26%)全身型。17例(63%)患儿MG相关致病抗体阳性,抗AchR抗体17例,其中1例MuSK抗体也阳性。利妥昔单抗作为一线免疫抑制剂13例,作为二线免疫抑制剂13例,作为三线免疫抑制剂1例。患儿应用利妥昔单抗前应用过的免疫抑制剂包括环孢素8例、他克莫司3例、硫唑嘌呤1例、吗替麦考酚酯1例和环孢素+硫唑嘌呤1例。利妥昔单抗用药年龄2~15岁,用药时间至少6个月,随访时间12个月以上。所有患儿接受利妥昔单抗治疗后末次随访时均达到改善及以上水平,14例(52%)达到完全稳定缓解,7例(26%)达到药物缓解,1例(4%)达到微小状态,5例(18%)病情改善。利妥昔单抗治疗后27例患儿均可以减少免疫调节治疗、缩短糖皮质激素疗程,22例(81%)患儿已减停激素治疗。在14例应用其他免疫抑制剂疗效欠佳患儿中,利妥昔单抗治疗后完全缓解7例。最常见的不良反应为呼吸道感染[4例(15%)]。仅2例对利妥昔单抗有过敏反应,经对症治疗后好转。结论利妥昔单抗对儿童MG具有良好的疗效和耐受性。早期应用利妥昔单抗有助于改善预后并缩短糖皮质激素疗程。

ObjectiveTo evaluate the efficacy and safety of rituximab in pediatric myasthenia gravis(MG).MethodsCase series study.The clinical manifestations,laboratory tests,treatment plans and prognosis of 27 pediatric MG patients treated with rituximab from June 2013 to June 2023 at Children′s Medical Center of Peking University First Hospital were retrospectively collected.ResultsThere were 5 males and 22 females in 27 MG children.The onset age was 2.1(1.6,4.8)years,ranging from 8 months to 11 years.The clinical classification included 20 children(74%)of ocular MG and 7 children(26%)of generalized MG.Seventeen children(63%)had positive MG-related pathogenic antibodies,including 17 children of anti-AchR antibody and 1 of them also had anti-MuSK antibody.Rituximab was used as first-line immunosuppressant in 13 children,second-line immunosuppressant in 13 children and third-line immunosuppressant in 1 child.Immunosuppressants used before rituximab including 8 children of cyclosporine,3 children of tacrolimus,1 child of azathioprine,1 child of mycophenolate mofetil and 1 child of cyclosporine combined with azathioprine.Rituximab was used for at least half a year with a follow-up period of more than 12 months.At the last follow-up after rituximab treatment,all children achieved improved or above,14 children(52%)achieved complete stable remission,7 children(26%)achieved pharmacologic remission,1 child(4%)achieved minimal manifestations,and 5 children(18%)improved.After rituximab treatment,27 children all could reduce the immunomodulation therapy and shorten the course of glucocorticoid therapy,and 22 children(81%)had stopped the glucocorticoid therapy.Among the 14 children with poor efficacy of other immunosuppressants,rituximab had complete stable remission of 7 children.The most common adverse reaction was respiratory infection(4 children(15%)).Only 2 children had allergic reaction to rituximab and got better after symptomatic treatment.ConclusionsRituximab has good efficacy and tolerance in pediatric MG.Early application of rituximab can improve the prognosis and shorten the course of glucocorticoid treatment.