BackgroundPatients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile. Here, we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM.MethodsData were pooled from two double-blind, placebo-controlled phase 3 trials; EVOLVE-1 and EVOLVE-2. Patients were 18–65 years old, experienced 4–14 monthly migraine headache days (MHDs) for ≥1 year prior, with onset at < 50 years of age. Migraine headaches were tracked via electronic patient-reported outcome system and randomization was stratified by low (LFEM; 4–7 monthly MHDs) or high (HFEM; 8–14 monthly MHDs) frequency. Subgroup analysis compared the HFEM and LFEM subgroups with a linear or generalized linear mixed model repeated measures approach.ResultsThe intent-to-treat patients (N = 1773) had a mean age of 41.3 years, were mostly white (75%), female (85%), and 66% of patients had HFEM. In both the LFEM and HFEM subgroups, the overall (Months 1–6) and monthly changes from baseline in monthly MHDs and monthly MHDs with acute medication use compared with placebo were statistically significantly reduced for galcanezumab 120-mg and 240-mg. Galcanezumab (120-mg and 240-mg) significantly decreased the overall and monthly MHDs with nausea and/or vomiting, and with photophobia and phonophobia versus placebo in patients with LFEM or HFEM. In both subgroups, the mean overall (Months 1–6) and monthly percentages of patients with ≥50%, ≥75%, and 100% reduction in monthly MHDs from baseline were statistically significantly greater in patients receiving either dose of galcanezumab versus placebo. Galcanezumab (120-mg and 240-mg) significantly improved the Migraine-Specific Quality of Life Questionnaire role function-restrictive domain score as well as the Migraine Disability Assessment total score versus placebo for patients with LFEM or HFEM. There were no significant subgroup-by-treatment interactions.ConclusionsGalcanezumab was as effective in patients with HFEM as in those with LFEM. Associated symptoms, quality of life, and disability were similarly improved in patients with HFEM or LFEM.Trial registrationNCT02614183, NCT02614196.

中文翻译：

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Galcanezumab 治疗发作性偏头痛：3 期研究（EVOLVE-1 和 EVOLVE-2）中偏头痛高频率与低频率的疗效亚组分析

背景高频发作性偏头痛 (HFEM) 患者比低频发作性偏头痛 (LFEM) 患者具有更大的疾病负担。急性治疗过度使用会增加 HFEM 患者偏头痛慢性化的风险。Galcanezumab 是一种结合降钙素基因相关肽 (CGRP) 的人源化单克隆抗体，可有效预防偏头痛，并具有良好的安全性。在这里，我们调查了 LFEM 或 HFEM 患者的 galcanezumab 疗效是否存在差异。方法数据来自两项双盲、安慰剂对照的 3 期试验；EVOLVE-1 和 EVOLVE-2。患者年龄为 18-65 岁，在 ≥1 年前经历 4-14 个月的偏头痛天数 (MHD)，发病年龄 < 50 岁。通过电子患者报告结果系统跟踪偏头痛，并按低（LFEM；每月 4-7 次 MHD）或高（HFEM；每月 8-14 次 MHD）频率对随机化进行分层。亚组分析将 HFEM 和 LFEM 亚组与线性或广义线性混合模型重复测量方法进行比较。 结果意向治疗患者 (N = 1773) 的平均年龄为 41.3 岁，主要是白人 (75%)、女性 ( 85%)，66% 的患者患有 HFEM。在 LFEM 和 HFEM 亚组中，与安慰剂相比，使用 galcanezumab 120-mg 和 240-mg 的每月 MHD 和每月 MHD 从基线的总体（第 1-6 个月）和每月变化与安慰剂相比显着降低。Galcanezumab（120 毫克和 240 毫克）显着降低总体和每月 MHD 并伴有恶心和/或呕吐，LFEM 或 HFEM 患者的畏光和畏声与安慰剂的比较。在这两个亚组中，接受任一剂量的 galcanezumab 与安慰剂的患者相比，每月 MHD 从基线降低 ≥50%、≥75% 和 100% 的平均总体（第 1-6 个月）和每月百分比在统计学上显着更高。对于 LFEM 或 HFEM 患者，与安慰剂相比，Galcanezumab（120 毫克和 240 毫克）显着改善了偏头痛特定生活质量问卷角色功能限制域评分以及偏头痛残疾评估总分。没有显着的亚组-治疗相互作用。结论 Galcanezumab 对 HFEM 患者与 LFEM 患者一样有效。HFEM 或 LFEM 患者的相关症状、生活质量和残疾同样得到改善。