Habib Ali A, Sacconi Sabrina, Antonini Giovanni, Cortés-Vicente Elena, Grosskreutz Julian, Mahuwala Zabeen K, Mantegazza Renato, Pascuzzi Robert M, Utsugisawa Kimiaki, Vissing John, Vu Tuan, Wiendl Heinz, Boehnlein Marion, Greve Bernhard, Woltering Franz, Bril Vera
MDA ALS and Neuromuscular Center, University of California, 200 South Manchester Avenue, Suite 110, Irvine, Orange, CA 92868, USA.
Peripheral Nervous System & Muscle Department, Pasteur 2 Hospital, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.
Ther Adv Neurol Disord. 2024 Sep 12;17:17562864241273036. doi: 10.1177/17562864241273036. eCollection 2024.
Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG.
To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study.
A randomised, double-blind, placebo-controlled phase III study.
Patients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II-IVa, Myasthenia Gravis Activities of Daily Living [MG-ADL] score ⩾3.0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11.0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed.
Overall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg ( = 5), 10 mg/kg ( = 8) or placebo ( = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), -7.28 (1.94); 10 mg/kg, -4.16 (1.78); and placebo, 2.28 (1.95). Rozanolixizumab 7 mg/kg LSM difference from placebo was -9.56 (97.5% confidence interval: -15.25, -3.87); 10 mg/kg, -6.45 (-11.03, -1.86). TEAEs were experienced by four (80.0%), five (62.5%) and three (37.5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred.
This subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies.
ClinicalTrials.gov: NCT03971422 (https://clinicaltrials.gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000968-18/GB).
肌肉特异性酪氨酸激酶（MuSK）自身抗体阳性（Ab+）的全身性重症肌无力（gMG）是gMG一种罕见且通常较为严重的亚型。
在MycarinG研究中评估rozanolixizumab在MuSK Ab+ gMG患者亚组中的疗效和安全性。
一项随机、双盲、安慰剂对照的III期研究。
乙酰胆碱受体（AChR）Ab+或MuSK Ab+ gMG患者（年龄≥18岁，美国重症肌无力基金会疾病分级II-IVa级，重症肌无力日常生活活动[MG-ADL]评分≥3.0[非眼部症状]，重症肌无力定量评分≥11.0）被随机分配（1:1:1），接受每周一次皮下注射rozanolixizumab 7 mg/kg、rozanolixizumab 10 mg/kg或安慰剂，持续6周，随后为8周观察期。随机分组按AChR和MuSK自身抗体状态分层。主要研究终点是从基线至第43天MG-ADL评分的变化。还评估了治疗中出现的不良事件（TEAE）。
总体而言，200例患者被随机分组，其中21例患有MuSK Ab+ gMG，接受rozanolixizumab 7 mg/kg（n = 5）、10 mg/kg（n = 8）或安慰剂（n = 8）。在MuSK Ab+ gMG患者中，观察到从基线至第43天MG-ADL评分的降低：rozanolixizumab 7 mg/kg最小二乘均值（LSM）变化（标准误）为-7.28（1.94）；10 mg/kg为-4.16（1.78）；安慰剂为2.28（1.95）。rozanolixizumab 7 mg/kg与安慰剂的LSM差异为-9.56（97.5%置信区间：-15.25，-3.87）；10 mg/kg为-6.45（-11.03，-1.86）。接受rozanolixizumab 7 mg/kg、10 mg/kg和安慰剂的MuSK Ab+ gMG患者分别有4例（80.0%）、5例（62.5%）和3例（37.5%）经历了TEAE。无患者经历严重TEAE。无死亡发生。
对参与MycarinG研究的成年MuSK Ab+ gMG患者进行的该亚组分析支持将rozanolixizumab用作患有MuSK自身抗体的gMG患者的一种有效治疗选择。
ClinicalTrials.gov：NCT03971422（https://clinicaltrials.gov/study/NCT03971422）；欧盟临床试验注册：EudraCT 2019-000968-18（https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000968-18/GB）
