Rozanolixizumab in generalized myasthenia gravis: Pooled analysis of the Phase 3 MycarinG study and two open-label extensions.

IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY
Journal of neuromuscular diseases Pub Date : 2025-03-01 Epub Date: 2025-03-04 DOI:10.1177/22143602241305511
Vera Bril, Artur Drużdż, Julian Grosskreutz, Ali A Habib, Renato Mantegazza, Sabrina Sacconi, Kimiaki Utsugisawa, Tuan Vu, Marion Boehnlein, Bernhard Greve, Maryam Gayfieva, Franz Woltering, Thaïs Tarancón, John Vissing
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引用次数: 0

Abstract

Background: Myasthenia gravis (MG) is a chronic autoimmune disease causing fluctuating muscle weakness. The MycarinG study showed that rozanolixizumab, a neonatal Fc receptor inhibitor, provided clinically meaningful improvements in MG outcomes in patients with acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) autoantibody-positive generalized MG (gMG).

Objective: We assessed efficacy and safety of 6-week rozanolixizumab treatment cycles in patients with gMG.

Methods: Following MycarinG, eligible patients enrolled in the open-label extension Phase 3 studies MG0004 (NCT04124965) to receive up to 52 weekly rozanolixizumab infusions or MG0007 (NCT04650854) to receive cycles of 6 weekly rozanolixizumab infusions (initiated on symptom worsening at investigators' discretion). To assess the effect of repeated cyclical treatment, data were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 (interim analysis). Efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Composite (MGC) and Quantitative Myasthenia Gravis (QMG) assessed in patients who received ≥2 symptom-driven treatment cycles. Treatment-emergent adverse events (TEAEs) were assessed in patients who received ≥1 cycle and had an (up to) 8-week follow-up period.

Results: At data cut-off (July 8, 2022), 188/196 (95.9%) patients received ≥1 treatment cycle with a follow-up period (primary safety pool; MycarinG/MG0007) and 127 (64.8%) received ≥2 symptom-driven cycles (primary efficacy pool; MycarinG/MG0004 [first 6 weeks]/MG0007). Consistent and clinically meaningful improvements in MG-ADL, MGC and QMG scores, and high MG-ADL, MGC and QMG response rates, were observed at the end of the first symptom-driven cycle and subsequent cycles. TEAEs were experienced by 169/188 (89.9%) patients and were mostly mild to moderate. TEAEs did not increase with repeated cycles.

Conclusions: Repeated cycles of rozanolixizumab resulted in consistent, clinically meaningful improvements across cycles in MG-specific outcomes with an acceptable safety profile, supporting rozanolixizumab as a treatment option for adults with AChR and MuSK autoantibody-positive gMG.

rozanolizumab治疗广泛性重症肌无力:3期MycarinG研究和两个开放标签扩展的汇总分析
背景:重症肌无力(MG)是一种引起波动性肌肉无力的慢性自身免疫性疾病。MycarinG研究显示,新生儿Fc受体抑制剂rozanolixizumab可改善乙酰胆碱受体(AChR)和肌肉特异性酪氨酸激酶(MuSK)自身抗体阳性的全身性MG (gMG)患者的MG预后。目的:我们评估6周罗扎利单抗治疗gMG患者的有效性和安全性。方法:在MycarinG之后,纳入开放标签扩展iii期研究MG0004 (NCT04124965)的符合条件的患者接受每周最多52次的罗扎利单抗输注,或MG0007 (NCT04650854)接受每周6次的罗扎利单抗输注周期(在症状恶化时开始,由研究者自行决定)。为了评估重复周期治疗的效果,数据汇集在MycarinG、MG0004(前6周)和MG0007(中期分析)中。疗效终点包括在接受≥2个症状驱动治疗周期的患者中评估的重症肌无力日常生活活动(MG-ADL)、重症肌无力复合(MGC)和定量重症肌无力(QMG)的基线变化。治疗出现的不良事件(teae)在接受≥1个周期的患者中进行评估,并进行(长达)8周的随访。结果:截止日期(2022年7月8日),188/196例(95.9%)患者接受了≥1个治疗周期和随访期(主要安全池;MycarinG/MG0007)和127例(64.8%)接受了≥2个症状驱动周期(主要疗效池;MycarinG/MG0004[前6周]/MG0007)。在第一个症状驱动周期和随后的周期结束时,观察到MG-ADL、MGC和QMG评分的一致和有临床意义的改善,以及MG-ADL、MGC和QMG的高缓解率。169/188例(89.9%)患者出现teae,多数为轻至中度。teae不随循环次数增加而增加。结论:rozanolixizumab的重复周期导致mg特异性结果的一致,临床有意义的改善,并且具有可接受的安全性,支持rozanolizumab作为AChR和MuSK自身抗体阳性的成人gMG的治疗选择。
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来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
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