Hewamadduma Channa, Freimer Miriam, Genge Angela, Leite M Isabel, Utsugisawa Kimiaki, Vu Tuan, Boroojerdi Babak, Grimson Fiona, Savic Natasa, Vanderkelen Mark, Howard James F
Academic Neuromuscular Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Sheffield Institute for Translational Neurosciences (SITraN), University of Sheffield, Sheffield, UK.
J Neurol. 2025 Jun 12;272(7):457. doi: 10.1007/s00415-025-13113-0.
The efficacy and safety of complement component 5 inhibitor zilucoplan in patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) were assessed in two double-blind studies (NCT03315130/NCT04115293 [RAISE]). During these studies and the first 12 weeks of the open-label extension study, RAISE-XT, corticosteroid and non-steroidal immunosuppressive therapy (NSIST) doses were kept stable; thereafter doses could be changed at the investigator's discretion. We evaluated corticosteroid and NSIST dose changes in patients with gMG during zilucoplan treatment in RAISE-XT.
In RAISE-XT, patients who completed a qualifying double-blind study self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. We assessed (post hoc) patients who changed their corticosteroid or NSIST dose relative to double-blind baseline at Week 120 (data cutoff: November 11, 2023).
Overall, 200 patients enrolled. At Week 120, 61.1% (n = 33/54) of patients who were on corticosteroids at double-blind baseline had reduced or discontinued corticosteroids (mean 15.5mg dose reduction); mean change from baseline (CFB) in Myasthenia Gravis Activities of Daily Living (MG-ADL) score:-6.55 (standard deviation [SD] 3.65). Of patients on NSIST at double-blind baseline, 29.8% (n = 14/47) reduced or discontinued ≥ 1 NSIST; mean CFB in MG-ADL score:-7.57 (SD 4.69). Among all patients at Week 120, 9.3% (n = 8/86) had increased or started corticosteroids; 2.4% of patients (n = 2/85) had increased NSIST, including one who started a new NSIST. Zilucoplan was well tolerated.
Treatment with zilucoplan allowed for reduction or discontinuation of corticosteroids in the majority of patients and NSIST in about a third of patients, while maintaining efficacy.
NCT04225871; October 2, 2019.
在两项双盲研究（NCT03315130/NCT04115293 [RAISE]）中评估了补体成分5抑制剂zilucoplan在抗乙酰胆碱受体抗体阳性全身型重症肌无力（gMG）患者中的疗效和安全性。在这些研究以及开放标签扩展研究RAISE-XT的前12周期间，皮质类固醇和非甾体免疫抑制疗法（NSIST）的剂量保持稳定；此后，剂量可由研究者自行决定更改。我们评估了RAISE-XT中接受zilucoplan治疗的gMG患者的皮质类固醇和NSIST剂量变化。
在RAISE-XT中，完成合格双盲研究的患者每日一次皮下自行注射0.3mg/kg的zilucoplan。我们评估了在第120周时相对于双盲基线改变了皮质类固醇或NSIST剂量的患者（事后分析）（数据截止日期：2023年11月11日）。
总体而言，共有200名患者入组。在第120周时，双盲基线时接受皮质类固醇治疗的患者中有61.1%（n = 33/54）减少或停用了皮质类固醇（平均剂量减少15.5mg）；重症肌无力日常生活活动（MG-ADL）评分相对于基线的平均变化（CFB）为-6.55（标准差[SD] 3.65）。双盲基线时接受NSIST治疗的患者中，29.8%（n = 14/47）减少或停用了≥1种NSIST；MG-ADL评分的平均CFB为-7.57（SD 4.69）。在第120周时的所有患者中，9.3%（n = 8/86）增加或开始使用皮质类固醇；2.4%的患者（n = 2/85）增加了NSIST，其中1人开始使用新的NSIST。zilucoplan耐受性良好。
使用zilucoplan进行治疗可使大多数患者减少或停用皮质类固醇，约三分之一的患者减少或停用NSIST，同时维持疗效。
NCT04225871；2019年10月2日。
