个体化间隔艾加莫德维持全身型重症肌无力微小表现状态：单臂、开放标签临床试验的研究方案

文献信息

中文摘要

引言： 艾加莫德是一种靶向新生儿Fc受体的人免疫球蛋白G1 Fc片段，可改善全身型重症肌无力（gMG）的症状。目前尚不清楚通过艾加莫德达到的微小表现（MM）状态能否长期持久维持，以及皮下（SC）自我给药是否能减轻治疗负担并支持生活质量。我们设计了一项前瞻性研究，以评估在间隔调整的艾加莫德给药下，使用低剂量口服泼尼松龙（PSL）≤ 5 mg/天（MM-5 mg）维持MM的情况。
方法： 这项单臂、开放标签、单中心探索性研究将纳入24名任何性别的成人（年龄18至<80岁）gMG患者，这些患者在既往试验或常规诊疗中，使用艾加莫德并口服PSL ≤ 5 mg/天（通常联用钙调神经磷酸酶抑制剂）已达到MM，定义为重症肌无力日常生活活动（MG-ADL）评分≤ 2或重症肌无力综合评分≤ 4。艾加莫德（静脉用艾加莫德α或皮下用艾加莫德α/透明质酸酶α）每周期每周给药一次，共4周。周期间隔根据最差每周MG-ADL评分个体化调整：恶化时缩短1周，连续两个稳定周期后延长1周。PSL和允许的背景口服免疫抑制剂保持不变。治疗持续最多55周，并设4周观察后随访期。
计划结局： 主要终点是在观察期间接受PSL ≤ 5 mg/天的情况下，按照预设的周期水平标准维持MM的患者比例。次要终点包括MG-ADL、重症肌无力综合评分、修订版15项重症肌无力生活质量问卷日文版（MG-QOL15r-J）和定量重症肌无力（QMG）评分的变化；患者报告的治疗便利性；血清免疫球蛋白G（IgG）变化；周期间隔分布；自身抗体滴度；以及从入组到因难以维持MM-5 mg而终止方案的时间。同时评估安全性。本文提供图形摘要。
临床试验注册： 日本临床试验注册中心（jRCT）：jRCTs031260127（于2026年5月14日前瞻性注册）。

英文摘要

INTRODUCTION: Efgartigimod, a human immunoglobulin G1 Fc fragment targeting the neonatal Fc receptor, improves symptoms in generalized myasthenia gravis (gMG). It remains unknown whether minimal manifestation (MM) status achieved with efgartigimod can be durably maintained over the long term, and whether subcutaneous (SC) self-administration reduces treatment burden and supports quality of life. We designed a prospective study to evaluate maintenance of MM with low-dose oral prednisolone (PSL) ≤ 5 mg/day (MM-5 mg) under interval-adjusted efgartigimod administration.
METHODS: This single-arm, open-label, single-center exploratory study will enroll 24 adults of either sex (aged 18 to < 80 years) with gMG who have achieved MM, defined as a Myasthenia Gravis Activities of Daily Living (MG-ADL) score ≤ 2 or MG Composite score ≤ 4, on efgartigimod with oral PSL ≤ 5 mg/day (commonly with a concomitant calcineurin inhibitor), in a preceding trial or routine care. Efgartigimod (intravenous efgartigimod alfa or SC efgartigimod alfa/vorhyaluronidase alfa) is given once weekly for 4 weeks per cycle. The intercycle interval is individualized from the worst weekly MG-ADL score: shortened by 1 week upon worsening, extended by 1 week after two stable cycles. PSL and permitted background oral immunosuppressants are held constant. Treatment lasts up to 55 weeks, with a 4-week post-observation period.
PLANNED OUTCOMES: The primary endpoint is the proportion of patients maintaining MM according to prespecified cycle-level criteria throughout the observation period while receiving PSL ≤ 5 mg/day. Secondary endpoints include changes in MG-ADL, MG Composite, the revised 15-item Myasthenia Gravis Quality of Life questionnaire, Japanese version (MG-QOL15r-J), and Quantitative MG (QMG) scores; patient-reported treatment convenience; change in serum immunoglobulin G (IgG); the intercycle-interval distribution; autoantibody titers; and the time from enrollment to protocol discontinuation due to difficulty maintaining MM-5 mg. Safety is also assessed. Graphical Abstract available for this article.
CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT): jRCTs031260127 (prospectively registered on 14 May 2026).