Bril Vera, Drużdż Artur, Grosskreutz Julian, Habib Ali A, Mantegazza Renato, Sacconi Sabrina, Utsugisawa Kimiaki, Vu Tuan, Boehnlein Marion, Greve Bernhard, Gayfieva Maryam, Woltering Franz, Tarancón Thaïs, Vissing John
University Health Network, Toronto, ON, Canada.
Department of Neurology, Municipal Hospital Poznań, Poznań, Poland.
J Neuromuscul Dis. 2025 Mar;12(2):218-230. doi: 10.1177/22143602241305511. Epub 2025 Mar 4.
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).
We assessed efficacy and safety of 6-week rozanolixizumab treatment cycles in patients with gMG.
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.
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.
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.
重症肌无力（MG）是一种慢性自身免疫性疾病，可导致肌肉无力波动。MycarinG研究表明，新生儿Fc受体抑制剂rozanolixizumab在乙酰胆碱受体（AChR）和肌肉特异性酪氨酸激酶（MuSK）自身抗体阳性的全身型重症肌无力（gMG）患者的MG结局方面带来了具有临床意义的改善。
我们评估了rozanolixizumab治疗6周周期对gMG患者的疗效和安全性。
在MycarinG研究之后，符合条件的患者参加了开放标签扩展3期研究MG0004（NCT04124965），接受每周一次的rozanolixizumab输注，最多52次，或MG0007（NCT04650854），接受每6周一次的rozanolixizumab输注周期（在研究者自行决定症状恶化时开始）。为了评估重复周期性治疗的效果，将MycarinG、MG0004（前6周）和MG0007（中期分析）的数据进行汇总。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）、重症肌无力综合评分（MGC）和重症肌无力定量评分（QMG）相对于基线的变化。在接受≥1个周期且有（最长）8周随访期的患者中评估治疗中出现的不良事件（TEAE）。
在数据截止时（2022年7月8日），188/196（95.9%）的患者接受了≥1个治疗周期并进入随访期（主要安全组；MycarinG/MG0007），127名（64.8%）患者接受了≥2个症状驱动周期（主要疗效组；MycarinG/MG0004[前6周]/MG0007）。在第一个症状驱动周期结束时及随后的周期中观察到MG-ADL、MGC和QMG评分持续且具有临床意义的改善，以及较高的MG-ADL、MGC和QMG缓解率。169/188（89.9%）的患者出现了TEAE，大多为轻度至中度。TEAE并未随着重复周期而增加。
rozanolixizumab的重复周期在MG特异性结局方面导致了各周期一致且具有临床意义的改善，安全性可接受，支持rozanolixizumab作为AChR和MuSK自身抗体阳性gMG成人患者的一种治疗选择。
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