Neuromuscular and Neuroimmunology Service, IRCCS Humanitas Clinical and Research Center, Milan University, Via Manzoni 56, Rozzano, Milan, 20089, Italy.
LFB, Les Ulis, France.
J Peripher Nerv Syst. 2020 Dec;25(4):356-365. doi: 10.1111/jns.12408. Epub 2020 Aug 31.
This prospective, multicenter, single-arm, open-label phase 3 study aimed to evaluate the efficacy and safety of IqYmune in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients received one induction dose of 2 g/kg and then seven maintenance doses of 1 g/kg at 3-week intervals. The primary endpoint was the responder rate at the end of study (EOS), defined as an improvement of ≥1 point on the adjusted inflammatory neuropathy cause and treatment (INCAT) disability scale. The responder rate was compared with the responder rate of a historical placebo group (33.3%). Secondary endpoints included changes from baseline to EOS of adjusted INCAT disability score, grip strength, Medical Research Council (MRC) sum score, Rasch-modified MRC sum score, Rasch-built overall disability scale score and the clinical global impression. Forty-two patients, including 23 Ig-naïve and 19 Ig-pre-treated, were included in the efficacy set. The overall response rate at EOS was 76.2% (95% confidence interval [60.5%-87.9%]). The superiority of IqYmune compared to the historical placebo control was demonstrated (P < .0001). The responder rate was numerically higher in Ig-pre-treated than in Ig-naïve patients but confidence intervals were overlapping (84.2% [60.4%-96.6%] vs 69.6% [47.1%-86.8%]). All secondary endpoints confirmed this conclusion. The median time to response was 15 weeks [8.9-19.1 weeks]. A total of 156 adverse events including five serious were considered related to IqYmune, 87.2% were mild. Neither hemolysis nor signs of renal or hepatic impairment were observed. These results demonstrate that IqYmune is an effective and well-tolerated treatment in patients with CIDP.
这项前瞻性、多中心、单臂、开放标签的 3 期研究旨在评估 IqYmune 在慢性炎症性脱髓鞘性多发性神经病(CIDP)患者中的疗效和安全性。患者接受 1 次 2g/kg 的诱导剂量,然后在 3 周间隔内接受 7 次 1g/kg 的维持剂量。主要终点是研究结束时(EOS)的应答率,定义为调整后的炎症性神经病病因和治疗(INCAT)残疾量表评分至少提高 1 分。应答率与历史安慰剂组(33.3%)的应答率进行比较。次要终点包括从基线到 EOS 时调整后的 INCAT 残疾评分、握力、医学研究委员会(MRC)总分、Rasch 修正 MRC 总分、Rasch 构建的整体残疾量表评分和临床总体印象的变化。42 例患者(包括 23 例 Ig 初治患者和 19 例 Ig 预处理患者)纳入疗效集。EOS 时的总应答率为 76.2%(95%置信区间[60.5%-87.9%])。与历史安慰剂对照相比,IqYmune 的优势得到了证明(P < .0001)。在 Ig 预处理患者中,应答率在数值上高于 Ig 初治患者,但置信区间重叠(84.2%[60.4%-96.6%] vs 69.6%[47.1%-86.8%])。所有次要终点都证实了这一结论。中位反应时间为 15 周[8.9-19.1 周]。共发生 156 例不良事件,包括 5 例严重不良事件,均认为与 IqYmune 有关,87.2%为轻度。未观察到溶血或肾功能或肝功能损害的迹象。这些结果表明,IqYmune 是 CIDP 患者有效且耐受良好的治疗方法。