利妥昔单抗治疗青少年重症肌无力：法国经验。

Rituximab Therapy in the Treatment of Juvenile Myasthenia Gravis: The French Experience.

机构信息

From the Hôpital Necker-Enfants Malades (A.M.), APHP; Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est (C.G., C.B., I.D.), Service de Neurologie pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris; Centre de Référence des Maladies Neuromusculaires de l'enfant PACARARE (F.A., B.C.), Service de Neuropédiatrie, Hôpital Timone Enfants, Marseille; Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est (A.I.), Service de Neuropédiatrie, Hôpital Trousseau, APHP, Paris; Centre de Référence des Maladies Neuromusculaires AOC (U.W.-L.), Service de Neuropédiatrie CHU Montpellier; Centre de Référence des Maladies Neuromusculaires AOC (C.C.), Unité de Neurologie Pédiatrique, Hôpital des Enfants CHU Toulouse; Centre de Référence des Maladies Neuromusculaires AOC (C.E.-T.), Unité de Neurologie pédiatrique, CHU Pellegrin, Bordeaux; Centre de référence des maladies neuromusculaires Nord Est Ile de France (J.-B.D.), CHU de Lille; Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est (S.Q.-R.), Hôpital Raymond Poincaré, APHP, Garches; and Service de pédiatrie (C.G.), Centre Hospitalier Intercommunal de Créteil, France.

出版信息

Neurology. 2022 Jun 7;98(23):e2368-e2376. doi: 10.1212/WNL.0000000000200288. Epub 2022 Mar 21.

DOI:10.1212/WNL.0000000000200288

PMID:35314497

Abstract

BACKGROUND AND OBJECTIVES: Corticosteroids are the first-line immunosuppressants in the management of juvenile myasthenia gravis despite their adverse effects. The place of new immunosuppressive therapies is not clearly defined by the last international consensus held in March 2019 due to the lack of clinical trials. The aim of this study is to describe the use of rituximab and its efficacy and safety in 8 main pediatric centers of the French neuromuscular reference network to propose a new place in the therapeutic strategy of juvenile myasthenia gravis. METHODS: We conducted a retrospective multicenter study from January 1, 2009, to April 30, 2020, including a large cohort of children with myasthenia gravis in 8 main French pediatric reference centers of the FILNEMUS network. The type of myasthenia, different lines of immunosuppressive treatment, and clinical course of the patients were collected. To evaluate the efficacy of rituximab, we studied the clinical course of patients on immunosuppressive therapy. Outcome was defined as the clinical and therapeutic status of patients at the last visit: stable without immunosuppressants, stable with immunosuppressants, or unstable. RESULTS: We included 74 patients: 18 children with ocular form and 56 children with generalized form. Of the 37 patients who required immunosuppressive therapy, 27 were treated with rituximab. Patients treated with rituximab had a better outcome than patients treated with conventional immunosuppressants ( = 0.006). The use of rituximab as a first-line immunosuppressant showed a better efficacy with a discontinuation of immunosuppressants in 75% of patients (vs 25%, = 0.04) and results in cortisone sparing (42% vs 92%, = 0.03) compared with rituximab treatment as a second- or third-line immunosuppression. Rituximab was well tolerated; no adverse effect was observed. DISCUSSION: The use of rituximab has increased in France over the last 10 years as a first-line immunosuppressant. This study suggests good tolerability and efficacy of rituximab in juvenile myasthenia gravis. Early use appears to improve outcomes and facilitate cortisone sparing in antibody-positive generalized juvenile myasthenia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for children with MG, rituximab is effective and well tolerated.

摘要

背景和目的：尽管皮质类固醇类药物存在不良反应，但仍是治疗小儿重症肌无力的一线免疫抑制剂。由于缺乏临床试验，2019 年 3 月举行的上一次国际共识会议并未明确界定新型免疫抑制疗法的地位。本研究旨在描述法国神经肌肉疾病参考网络的 8 个主要儿科中心使用利妥昔单抗的情况及其疗效和安全性，以期为小儿重症肌无力的治疗策略提供新的依据。

方法：我们进行了一项回顾性多中心研究，纳入了 2009 年 1 月 1 日至 2020 年 4 月 30 日期间，来自法国 FILNEMUS 网络 8 个主要儿科参考中心的患有重症肌无力的大量患儿。收集了重症肌无力的类型、不同的免疫抑制治疗方案以及患儿的临床病程。为了评估利妥昔单抗的疗效，我们研究了接受免疫抑制治疗的患儿的临床病程。疗效定义为最后一次就诊时患儿的临床和治疗状况：无免疫抑制剂的稳定状态、有免疫抑制剂的稳定状态或不稳定状态。

结果：我们共纳入 74 例患儿：18 例为眼肌型，56 例为全身型。在需要免疫抑制治疗的 37 例患儿中，27 例接受了利妥昔单抗治疗。与接受传统免疫抑制剂治疗的患儿相比，接受利妥昔单抗治疗的患儿的疗效更好（ = 0.006）。将利妥昔单抗作为一线免疫抑制剂使用，在 75%的患者中可停用免疫抑制剂（而使用传统免疫抑制剂的患者中这一比例为 25%， = 0.04），且可节省皮质类固醇（42% vs 92%， = 0.03），优于将利妥昔单抗作为二线或三线免疫抑制剂使用。利妥昔单抗耐受性良好，未观察到不良反应。

讨论：过去 10 年来，利妥昔单抗在法国的使用有所增加，作为一线免疫抑制剂。本研究提示利妥昔单抗治疗小儿重症肌无力具有良好的疗效和耐受性。早期使用可能改善疗效，有助于节省皮质类固醇类药物在抗体阳性的全身型小儿重症肌无力患者中的应用。

证据分类：本研究提供了 III 级证据，表明对于患有重症肌无力的儿童，利妥昔单抗是有效且耐受良好的。