Diener Hans-Christoph, Day Kathleen A, Lipsius Sarah, Aurora Sheena K, Hindiyeh Nada A, Detke Holland C
Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
Eli Lilly and Company, Indianapolis, IN, USA.
J Headache Pain. 2025 Feb 3;26(1):26. doi: 10.1186/s10194-025-01956-x.
Chronic migraine (CM) is a highly disabling form of migraine in which patients have ≥ 15 headache days per month, of which at least 8 have the features of migraine. Galcanezumab is a monoclonal antibody to calcitonin gene-related peptide which is approved for the preventive treatment of migraine. Ability to convert patients from chronic migraine frequency to episodic migraine (EM) frequency is a clinically relevant and desirable outcome when prescribing preventive treatments to patients with CM.
Patients aged 18-65 years with an ICHD-3β diagnosis of CM were randomized 2:1:1 to receive monthly injections of placebo (N = 558), galcanezumab 120 mg with a 240-mg loading dose (N = 278), or galcanezumab 240 mg (N = 277) during a 3-month double-blind period of the phase 3 REGAIN trial. Patients could subsequently enter a 9-month open-label extension in which they received galcanezumab 120 mg or 240 mg/month per investigator's discretion. In this post-hoc analysis, we assessed the percentages of patients who shifted to EM (< 8 migraine headache days or < 15 headache days/month), low frequency EM (LFEM; <8 migraine headache days/month), and very low frequency EM (VLFEM; <4 migraine headache days/month) for at least 3 consecutive months. Double-blind percentage comparisons versus placebo represent modeled estimates from raw rates.
At baseline, patients had a mean of 19.4 migraine headache days per month (SD = 4.5) and 21.4 headache days per month (SD = 4.1). During the 3-month double-blind treatment period, a greater percentage of galcanezumab-treated patients shifted to EM frequency and maintained it across all 3 months (31.5%) than did placebo-treated patients (19.8%, p < 0.001). Among galcanezumab-treated patients across the entire 12-month trial, 65.1% shifted from CM to EM frequency, with 44.2% shifting to LFEM and 21.5% shifting to VLFEM for ≥ 3 consecutive months. Proportions of patients shifting from CM to EM frequency for ≥ 3 consecutive months and until last patient visit were: 55.0% to EM; 33.4% to LFEM; 13.9% to VLFEM.
These results suggest that galcanezumab helped a majority of patients convert from chronic to episodic migraine frequency over the course of this 12-month study.
Clinicaltrials.gov NCT02614261, first registered November 25, 2015.
慢性偏头痛（CM）是偏头痛的一种高度致残形式，患者每月头痛天数≥15天，其中至少8天具有偏头痛特征。加卡尼单抗是一种针对降钙素基因相关肽的单克隆抗体，已被批准用于偏头痛的预防性治疗。对于CM患者开具预防性治疗药物时，将患者从慢性偏头痛发作频率转变为发作性偏头痛（EM）频率的能力是一个具有临床相关性且理想的结果。
年龄在18 - 65岁、国际头痛疾病分类第三版beta版（ICHD-3β）诊断为CM的患者，在3期REGAIN试验的3个月双盲期内，按2:1:1随机分组，分别接受每月一次的安慰剂注射（N = 558）、负荷剂量240 mg后每月120 mg的加卡尼单抗（N = 278）或每月240 mg的加卡尼单抗（N = 277）。患者随后可进入为期9个月的开放标签延长期，在此期间，研究者可自行决定让患者每月接受120 mg或240 mg的加卡尼单抗治疗。在这项事后分析中，我们评估了连续至少3个月转变为EM（每月偏头痛头痛天数<8天或头痛天数<15天）、低频EM（LFEM；每月偏头痛头痛天数<8天）和极低频率EM（VLFEM；每月偏头痛头痛天数<4天）的患者百分比。与安慰剂的双盲百分比比较代表根据原始率进行的模型估计。
基线时，患者每月平均偏头痛头痛天数为19.4天（标准差 = 4.5），每月头痛天数为21.4天（标准差 = 4.1）。在3个月的双盲治疗期内，接受加卡尼单抗治疗的患者转变为EM频率并在所有3个月中维持该频率的百分比（31.5%）高于接受安慰剂治疗的患者（仅19.8%，p < 0.001）。在整个12个月试验中接受加卡尼单抗治疗的患者中，65.1%从CM转变为EM频率，其中44.2%转变为LFEM，21.5%连续≥3个月转变为VLFEM。连续≥3个月直至最后一次患者访视时从CM转变为EM频率的患者比例分别为：55.0%转变为EM；33.4%转变为LFEM；13.9%转变为VLFEM。
这些结果表明，在这项为期12个月的研究过程中，加卡尼单抗帮助大多数患者从慢性偏头痛转变为发作性偏头痛频率。
Clinicaltrials.gov NCT02614261，首次注册于2015年11月25日。
