Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA, USA.
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA.
J Headache Pain. 2019 Jun 28;20(1):75. doi: 10.1186/s10194-019-1024-x.
Patients 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.
Data 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.
The 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.
Galcanezumab 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.
NCT02614183 , NCT02614196 .
高频发作性偏头痛（HFEM）患者的疾病负担比低频发作性偏头痛（LFEM）患者更重。急性治疗过度会增加 HFEM 患者偏头痛慢性化的风险。加奈珠单抗是一种与人源化单克隆抗体结合降钙素基因相关肽（CGRP），具有良好的安全性，对偏头痛预防有效。在此，我们研究 LFEM 或 HFEM 患者中加奈珠单抗疗效是否存在差异。
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 18-65 岁，在之前至少 1 年中每月有 4-14 次偏头痛发作（MHD），发病年龄<50 岁。偏头痛头痛通过电子患者报告结局系统进行跟踪，随机分组根据低（LFEM；每月 4-7 次 MHD）或高（HFEM；每月 8-14 次 MHD）频率进行分层。亚组分析采用线性或广义线性混合模型重复测量方法比较 HFEM 和 LFEM 亚组。
意向治疗患者（N=1773）的平均年龄为 41.3 岁，大多数为白人（75%），女性（85%），66%的患者为 HFEM。在 LFEM 和 HFEM 亚组中，与安慰剂相比，加奈珠单抗 120mg 和 240mg 在总体（第 1-6 个月）和每月从基线的每月 MHDs 和每月使用急性药物的 MHDs 变化方面均有统计学意义的减少。加奈珠单抗（120mg 和 240mg）与 LFEM 或 HFEM 患者的安慰剂相比，显著减少了总体（第 1-6 个月）和每月伴有恶心和/或呕吐、畏光和畏声的 MHDs。在两个亚组中，与安慰剂相比，接受加奈珠单抗任何剂量治疗的患者每月从基线的 MHDs 至少减少 50%、75%和 100%的总体（第 1-6 个月）和每月百分比均有统计学意义。加奈珠单抗（120mg 和 240mg）与 LFEM 或 HFEM 患者的安慰剂相比，偏头痛特异性生活质量问卷角色功能受限域评分以及偏头痛残疾评估总分均有显著改善。没有发现治疗与亚组之间的显著交互作用。
加奈珠单抗在 HFEM 患者中的疗效与 LFEM 患者相同。HFEM 或 LFEM 患者的伴随症状、生活质量和残疾同样得到改善。
NCT02614183，NCT02614196。
Zotero 插件
