From Eli Lilly and Company, Indianapolis, IN (H.C.D., S.W., K.J.S., S.K.A.); Department of Neurology (P.J.G.), NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, UK; University of California (P.J.G.), San Francisco; and Departments of Neurology and Neurotherapeutics and Ophthalmology, University of Texas Southwestern Medical Center, Dallas.
Neurology. 2018 Dec 11;91(24):e2211-e2221. doi: 10.1212/WNL.0000000000006640. Epub 2018 Nov 16.
To evaluate the efficacy and safety of galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, in the preventive treatment of chronic migraine.
A phase 3, randomized, double-blind, placebo-controlled study of LY2951742 in patients with chronic migraine (Evaluation of Galcanezumab in the Prevention of Chronic Migraine [REGAIN]) was a phase 3 study with a 3-month double-blind, placebo-controlled treatment phase and a 9-month open-label extension. Eligible patients 18 to 65 years of age with chronic migraine were randomized 2:1:1 to monthly subcutaneous injections of placebo (n = 558), galcanezumab 120 mg (with a 240-mg loading dose, n = 278), or galcanezumab 240 mg (n = 277). The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days (MHDs) during the 3-month double-blind treatment phase.
Mean number of monthly MHDs at baseline was 19.4 for the total sample. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo -2.7, galcanezumab 120 mg -4.8, galcanezumab 240 mg -4.6) ( < 0.001 for each dose compared to placebo). There were no clinically meaningful differences between galcanezumab doses and placebo on any safety or tolerability outcome except for a higher incidence of treatment-emergent injection-site reaction ( < 0.01), injection-site erythema ( < 0.001), injection-site pruritus ( < 0.01), and sinusitis ( < 0.05) in the galcanezumab 240-mg group relative to placebo.
Both doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.
NCT02614261.
This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.
评估降钙素基因相关肽（CGRP）人源化单克隆抗体加奈珠单抗治疗慢性偏头痛的疗效和安全性。
这是一项在慢性偏头痛患者中开展的为期 3 个月的随机、双盲、安慰剂对照的 LY2951742 评估试验（预防慢性偏头痛的加奈珠单抗评估[REGAlN]），也是一项 3 期研究，包含 3 个月的双盲对照治疗期和 9 个月的开放标签扩展期。18 至 65 岁的慢性偏头痛患者按 2:1:1 的比例随机分配，每月接受皮下注射安慰剂（n = 558）、加奈珠单抗 120 mg（初始剂量 240 mg，n = 278）或加奈珠单抗 240 mg（n = 277）。主要终点为双盲治疗期 3 个月内每月偏头痛发作天数（MHD）的总体平均变化。
总体样本的基线每月 MHD 平均值为 19.4。与安慰剂相比，加奈珠单抗两个剂量组每月 MHD 数均有更大的总体平均降低（安慰剂-2.7，加奈珠单抗 120 mg-4.8，加奈珠单抗 240 mg-4.6）（各剂量组与安慰剂相比，均＜0.001）。除注射部位反应（＜0.01）、注射部位红斑（＜0.001）、注射部位瘙痒（＜0.01）和鼻窦炎（＜0.05）的发生率较高外，加奈珠单抗各剂量组与安慰剂相比，在任何安全性或耐受性结果方面均无临床意义差异。
加奈珠单抗两个剂量均优于安慰剂，能减少每月 MHD 数。加奈珠单抗治疗慢性偏头痛预防有效，且安全耐受良好。
NCT02614261。
这项干预性研究提供了 I 级证据，表明加奈珠单抗在减少每月 MHD 数方面优于安慰剂。
