美国加州伦德贝克La Jolla研究中心Roger Cady联合佛州棕榈滩头痛中心Paul K. Winner团队比较了静脉输注eptinezumab与安慰剂对偏头痛发作时疼痛和最烦人症状的影响。相关论文于2021年6月15日发表在《美国医学会杂志》上。

静脉输注eptinezumab，一种抗降钙素基因相关肽抗体，已被批准用于预防成人偏头痛。在输注后的第1天即已确定预防效果。

为了评估偏头痛发作期间采用eptinezumab治疗的相关疗效和不良事件，2019年11月4日至2020年7月8日，研究组在美国和格鲁吉亚的47个机构进行了一项临床3期、多中心、平行组、双盲、随机、安慰剂对照试验。招募年龄为18-75岁、有1年以上的偏头痛病史、筛查前3个月每月偏头痛4-15天，在中度至重度偏头痛发作期间接受治疗的参与者，并将其随机分组，其中238例接受eptinezumab治疗，242例接受安慰剂治疗，在中度至重度偏头痛发病1-6小时内进行静脉输注。

共同主要疗效终点为头痛的疼痛缓解时间和无最烦人症状（恶心、畏光或声音恐惧）时间。关键次要终点为开始注射后2小时头痛的疼痛缓解时间和无最烦人症状时间。其他次要终点为4小时头痛的疼痛缓解时间和无最烦人症状时间，以及24小时内使用救援性药物。

480名接受随机治疗的患者平均年龄为44岁，84%为女性，共有476人完成了研究。Eptinezumab组患者的中位头痛疼痛缓解时间为4小时，显著短于安慰剂组的9小时；中位无最烦人症状时间为2小时，显著短于安慰剂组的3小时。输注后2小时，eptinezumab组中有23.5%的患者头痛疼痛缓解，显著高于安慰剂组的12.0%；55.5%的患者不再出现最烦人症状，显著高于安慰剂组的35.8%。

该结果在输注后4小时仍有统计学意义。Eptinezumab组中有31.5%的患者在24小时内使用救援性药物，显著低于安慰剂组的59.9%，差异具有统计学意义。Eptinezumab组和安慰剂组分别有10.9%和10.3%的患者发生治疗性紧急不良事件，其中最常见的是过敏（均在eptinezumab组）。两组均未发生治疗性紧急严重不良事件。

研究结果表明，在符合接受预防性偏头痛治疗的中度至重度偏头痛发作的患者中，静脉输注eptinezumab与安慰剂相比，可显著缩短头痛发作时间，症状缓解更快。

附：英文原文

Title: Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack: A Randomized Clinical Trial

Author: Paul K. Winner, Peter McAllister, George Chakhava, Jessica Ailani, Anders Ettrup, Mette Krog Josiassen, Annika Lindsten, Lahar Mehta, Roger Cady

Issue&Volume: 2021/06/15

Abstract:

Importance  Intravenous eptinezumab, an anti–calcitonin gene-related peptide antibody, is approved for migraine prevention in adults. It has established onset of preventive efficacy on day 1 after infusion.

Objective  To evaluate the efficacy of and adverse events related to eptinezumab when initiated during a migraine attack.

Design, Setting, and Participants  Phase 3, multicenter, parallel-group, double-blind, randomized, placebo-controlled trial conducted from November 4, 2019, to July 8, 2020, at 47 sites in the United States and the country of Georgia. Participants (aged 18-75 years) with a greater than 1-year history of migraine and migraine on 4 to 15 days per month in the 3 months prior to screening were treated during a moderate to severe migraine attack.

Interventions  Eptinezumab, 100 mg (n=238), or placebo (n=242), administered intravenously within 1 to 6 hours of onset of a qualifying moderate to severe migraine.

Main Outcomes and Measures  Co-primary efficacy end points were time to headache pain freedom and time to absence of most bothersome symptom (nausea, photophobia, or phonophobia). Key secondary end points were headache pain freedom and absence of most bothersome symptom at 2 hours after start of infusion. Additional secondary end points were headache pain freedom and absence of most bothersome symptom at 4 hours and use of rescue medication within 24 hours.

Results  Of 480 randomized and treated patients (mean age, 44 years; 84% female), 476 completed the study. Patients treated with eptinezumab vs placebo, respectively, achieved statistically significantly faster headache pain freedom (median, 4 hours vs 9 hours; hazard ratio, 1.54 [P<.001]) and absence of most bothersome symptom (median, 2 hours vs 3 hours; hazard ratio, 1.75 [P<.001]). At 2 hours after infusion, in the respective eptinezumab and placebo groups, headache pain freedom was achieved by 23.5% and 12.0% (between-group difference, 11.6% [95% CI, 4.78%-18.31%]; odds ratio, 2.27 [95% CI, 1.39-3.72]; P<.001) and absence of most bothersome symptom by 55.5% and 35.8% (between-group difference, 19.6% [95% CI, 10.87%-28.39%]; odds ratio, 2.25 [95% CI, 1.55-3.25]; P<.001). Results remained statistically significant at 4 hours after infusion. Statistically significantly fewer eptinezumab-treated patients used rescue medication within 24 hours than did placebo patients (31.5% vs 59.9%, respectively; between-group difference, 28.4% [95% CI, 36.95% to 19.86%]; odds ratio, 0.31 [95% CI, 0.21-0.45]; P<.001). Treatment-emergent adverse events occurred in 10.9% of the eptinezumab group and 10.3% of the placebo group; the most common was hypersensitivity (eptinezumab, 2.1%; placebo, 0%). No treatment-emergent serious adverse events occurred.

Conclusions and Relevance  Among patients eligible for preventive migraine therapy experiencing a moderate to severe migraine attack, treatment with intravenous eptinezumab vs placebo shortened time to headache and symptom resolution. Feasibility of administering eptinezumab treatment during a migraine attack and comparison with alternative treatments remain to be established.

DOI: 10.1001/jama.2021.7665

Source: https://jamanetwork.com/journals/jama/article-abstract/2781053