GomezMancilla Baltazar, Meriggioli Matthew N, Genge Angela, Roubenoff Ronenn, Espié Pascal, Dupuy Cyrielle, Hartmann Nicole, Pezous Nicole, Kinhikar Arvind, Tichy Mia, Dionne Annie, Vissing John, Andersen Henning, Schoser Benedikt, Meisel Andreas, Jordan Berit, Devlikamova Farida, Poverennova Irina, Stuchevskaya Fatima, Lin Thy-Sheng, Rush James S, Gergely Peter
Novartis Institutes for BioMedical Research, Basel, Switzerland.
Novartis Biomedical Research, Cambridge, MA, USA.
J Clin Neurosci. 2024 Jan;119:76-84. doi: 10.1016/j.jocn.2023.11.013. Epub 2023 Nov 20.
Increased morbidity in many patients with myasthenia gravis (MG) on long-term immunosuppression highlights the need for improved treatments. The aim of this study is to investigate the safety and efficacy of iscalimab (CFZ533), a fully human anti-CD40 monoclonal antibody, in patients with moderate-to-severe MG receiving standard-of-care (SoC) therapies.
In this double-blind, placebo-controlled phase 2 study, symptomatic patients (n = 44) despite SoC were randomized 1:1 to receive intravenous iscalimab (10 mg/kg; n = 22) or placebo (n = 22) every 4 weeks for 6 doses in total. Patients were followed up for 6 months after the last dose. The total duration of the study was 52 weeks.
In total, 34 of 44 patients (77.3 %) completed the study. The primary endpoint, Quantitative MG score, did not change significantly between baseline and week 25 for iscalimab (median [90 % CI], -4.07 [-5.67, -2.47]) versus placebo (-2.93 [-4.53, -1.33]); however, non-thymectomized patients (n = 29) showed more favorable results (iscalimab, -4.35 [-6.07, -2.64] vs placebo, -2.26 [-4.16, -0.36]). A statistically significant difference between iscalimab and placebo groups was observed in MG Composite score (adjusted mean change: -4.19 [-6.67, -1.72]; p = 0.007) at week 13, and MG-Activities of Daily Living score (-1.93 [-3.24, -0.62]; p = 0.018) at week 21. Adverse events were comparable between the iscalimab (91 %) and placebo (96 %) groups.
Iscalimab showed favorable safety and improvements compared with placebo in non-thymectomized patients with moderate-to-severe MG. It did not show any protective effect in patients with moderate-to-severe MG.
许多长期接受免疫抑制治疗的重症肌无力（MG）患者发病率增加，这凸显了改进治疗方法的必要性。本研究的目的是调查全人源抗CD40单克隆抗体伊斯卡利单抗（CFZ533）在接受标准治疗（SoC）的中重度MG患者中的安全性和有效性。
在这项双盲、安慰剂对照的2期研究中，尽管接受了SoC治疗但仍有症状的患者（n = 44）按1:1随机分组，每4周静脉注射伊斯卡利单抗（10 mg/kg；n = 22）或安慰剂（n = 22），共6剂。最后一剂后对患者进行6个月的随访。研究总时长为52周。
44例患者中共有34例（77.3%）完成了研究。主要终点指标定量MG评分在基线至第25周期间，伊斯卡利单抗组（中位数[90%CI]，-4.07[-5.67，-2.47]）与安慰剂组（-2.93[-4.53，-1.33]）之间无显著变化；然而，未行胸腺切除术的患者（n = 29）显示出更有利的结果（伊斯卡利单抗组，-4.35[-6.07，-2.64] vs安慰剂组，-2.26[-4.16，-0.36]）。在第13周时，伊斯卡利单抗组和安慰剂组在MG综合评分（调整后平均变化：-4.19[-6.67，-1.72]；p = 0.007）以及第21周时在MG日常生活活动评分（-1.93[-3.24，-0.62]；p = 0.018）方面观察到有统计学意义的差异。伊斯卡利单抗组（91%）和安慰剂组（96%）的不良事件发生率相当。
在未行胸腺切除术的中重度MG患者中，与安慰剂相比，伊斯卡利单抗显示出良好的安全性并带来了改善。但在中重度MG患者中未显示出任何保护作用。
