Jensen Rigmor H, Tassorelli Cristina, Tepper Stewart J, Charles Andrew, Goadsby Peter J, Snoer Agneta H, Sperling Bjørn, Krog Josiassen Mette, Borgen Linander Christine, Ettrup Anders, Boneva Neli
Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark.
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
JAMA Neurol. 2025 May 19. doi: 10.1001/jamaneurol.2025.1317.
Cluster headache, characterized by bouts of excruciating pain attacks, detrimentally affects health and quality of life. Eptinezumab is an anticalcitonin gene-related peptide monoclonal antibody approved for migraine prevention.
To evaluate the efficacy and safety of eptinezumab in the preventive treatment of episodic cluster headache.
DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, randomized (1:1) clinical trial (Eptinezumab in Participants With Episodic Cluster Headache [ALLEVIATE]) was conducted between December 2020 and October 2023. Results are from the initial 4-week randomized phase. The study took place at 64 sites across Europe, the US, and Japan. Included were adults (aged 18-75 years) with a history of episodic cluster headache for 1 or more years (with bouts lasting ≥6 weeks when untreated) and previous acute and preventive medication use.
Eptinezumab, 400 mg, or placebo (intravenous infusion).
The primary end point was the change from baseline in the number of weekly attacks in weeks 1 to 2. Safety was assessed using treatment-emergent adverse events.
Of 628 total participants screened, 320 entered the second screening period, and 231 met eligibility criteria. Of the 231 participants randomized (eptinezumab, n = 118; placebo, n = 113), 215 (93%) completed the placebo-controlled period. The participant mean (SD) age was 44 (11) years, and 178 of 229 were male (78%). At baseline, the mean (SD) weekly attacks were 15.2 (8.1) in the eptinezumab group and 15.7 (8.3) in the placebo group. There was no statistically significant difference between eptinezumab and placebo in the change from baseline in the number of weekly attacks over weeks 1 to 2 (least-squares mean [SE], -4.0 [0.93] vs -4.6 [0.89]; between-group difference, 0.7; 95% CI, -1.3 to 2.6; P = .50). More eptinezumab-treated participants achieved 50% or greater response vs placebo over week 2 (50.9% [54 of 106] vs 37.3% [41 of 110]; odds ratio [OR], 1.77; 95% CI, 1.03-3.07; P =.04), week 3 (62.5% [65 of 104] vs 43.8% [49 of 112]; OR, 2.26; 95% CI, 1.30-3.97; P =.004), and week 4 (66.7% [68 of 102] vs 50.5% [54 of 107]; OR, 2.14; 95% CI, 1.21-3.83; P =.009). Eptinezumab showed numerically larger improvements than placebo for 75% or greater response, average daily pain scores, and across other patient-reported outcomes. Treatment-emergent adverse events occurred in 25.0% of patients (28 of 112) receiving eptinezumab and 26.5% of patients (31 of 117) receiving placebo.
Among adults with episodic cluster headache, eptinezumab did not significantly reduce the number of attacks vs placebo, although it was associated with numerically higher responder rates and improvements in average daily pain and patient-reported outcomes. Eptinezumab was generally well tolerated.
ClinicalTrials.gov Identifier: NCT04688775.
丛集性头痛以剧烈疼痛发作为特征，对健康和生活质量有不利影响。eptinezumab是一种已获批用于预防偏头痛的抗降钙素基因相关肽单克隆抗体。
评估eptinezumab预防性治疗发作性丛集性头痛的疗效和安全性。
设计、设置和参与者：这项双盲、安慰剂对照、随机（1:1）临床试验（发作性丛集性头痛患者使用eptinezumab [缓解]）于2020年12月至2023年10月进行。结果来自最初的4周随机阶段。该研究在欧洲、美国和日本的64个地点进行。纳入的是有1年或更长时间发作性丛集性头痛病史（未治疗时发作持续≥6周）且既往使用过急性和预防性药物的成年人（年龄18 - 75岁）。
400毫克eptinezumab或安慰剂（静脉输注）。
主要终点是第1至2周每周发作次数相对于基线的变化。使用治疗中出现的不良事件评估安全性。
在总共628名筛查的参与者中，320人进入第二筛查期，231人符合入选标准。在231名随机分组的参与者中（eptinezumab组，n = 118；安慰剂组，n = 113），215人（93%）完成了安慰剂对照期。参与者的平均（标准差）年龄为44（11）岁，229名中有178名男性（78%）。基线时，eptinezumab组每周发作的平均（标准差）次数为15.2（8.1）次，安慰剂组为15.7（8.3）次。在第1至2周每周发作次数相对于基线的变化方面，eptinezumab与安慰剂之间无统计学显著差异（最小二乘均值[标准误]，-4.0 [0.93] 对 -4.6 [0.89]；组间差异，0.7；95%置信区间，-1.3至2.6；P = 0.50）。在第2周（50.9% [106人中的54人] 对37.3% [110人中的41人]；优势比[OR]，1.77；95%置信区间，1.03 - 3.07；P = 0.04）、第3周（62.5% [104人中的65人] 对43.8% [112人中的49人]；OR，2.26；95%置信区间，1.
