西班牙巴塞罗那自治大学Patricia Pozo-Rosich团队研究了Atogepant预防性治疗慢性偏头痛的疗效与安全性。该研究于2023年7月26日发表在《柳叶刀》杂志上。
这项研究旨在评估Atogepant预防性治疗慢性偏头痛的疗效、安全性和耐受性。
研究组在美国、英国、加拿大、中国、捷克共和国、丹麦、法国、德国、意大利、日本、韩国、波兰、俄罗斯、西班牙、瑞典的142个临床研究点进行了这项随机、双盲、安慰剂对照的3期临床试验。年龄在18-80岁、有1年及以上慢性偏头痛病史的成年人被随机分配（1:1:1）接受口服Atogepant 30 mg，每天两次；60 mg每天一次，或安慰剂。主要终点是12周治疗期间每月平均偏头痛天数（MMD）与基线相比的变化。
主要分析是在改良意向治疗人群中进行的，包括所有随机分配的参与者，他们至少接受了一剂研究干预，有可评估的电子日记（eDiary）数据基线期，并且在双盲期内至少有一个可评估的基线后4周期（1-4、5-8和9-12周）的电子日记数据。安全人群包括所有至少接受一剂研究干预的参与者。
2019年3月11日至2022年1月20日，共有1489名参与者接受了资格评估。711人被排除在外，778名参与者被随机分配到Atogepant 30 mg，每天两次（n=257），Atogepant 60 mg，每天一次（n=262）或安慰剂（n=259）。安全人群的参与者年龄为18-74岁（平均42.1岁）。773名患者中459名（59%）为白人，677名（88%）为女性，96名（12%）为男性。84名参与者在试验期间停止了治疗，755名参与者包括改良意向治疗人群（Atogepant 30 mg，每天两次，n=253，Atogepant 60 mg，每天一次，n=256，安慰剂n=246）。
基线平均MMD数为：Atogepant 30 mg每日两次组为18.6（SE 5.1），Atogepant 60 mg每日一次组为19.2（5.3），安慰剂组为18.9（4.8）。与基线相比，Atogepant 30 mg，每天两次组的12周内平均MMD的变化为−7.5（SE 0.4），Atogepant 60 mg，每天一次组为−6.9（0.4），安慰剂组为−5.1（0.4）。与安慰剂的最小二乘平均差为−2.4（校正后的p<0.0001）和−1.8（校正后p=0.0009）。
Atogepant最常见的不良事件是便秘（每天两次30 mg组有28人[10.9%]；每天一次60 mg组有26名[10%]；安慰剂组8名[3%]）和恶心（每天两次30 mg组20名[8%]；每日一次60 mg组25名[10%]和安慰剂组9名[4%]）。在每个治疗组中观察到潜在的临床显著体重减轻（基线后任何时间减轻≥7%）（Atogepant 30 mg，每天两次组14名[6]；Atogepant 60 mg，每天一次组有15名[6]；安慰剂组有3名[2]）。
研究结果表明，对于慢性偏头痛患者，30 mg Atogepant每日两次和60 mg Atogepant每日一次的适应剂治疗12周，显示MMD的临床相关减少。两种剂量的Atogepant都具有良好的耐受性，与Atogepant的已知安全性一致。
附：英文原文
Title: Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial
Author: Patricia Pozo-Rosich, Jessica Ailani, Messoud Ashina, Peter J Goadsby, Richard B Lipton, Uwe Reuter, Hua Guo, Brittany Schwefel, Kaifeng Lu, Ramesh Boinpally, Rosa Miceli, Rosa De Abreu Ferreira, Emily McCusker, Sung Yun Yu, Lawrence Severt, Michelle Finnegan, Joel M Trugman
Issue&Volume: 2023-07-26
Abstract:
Background
In this study, we aimed to evaluate the efficacy, safety, and tolerability of atogepant for the preventive treatment of chronic migraine.
Methods
We did this randomised, double-blind, placebo-controlled, phase 3 trial at 142 clinical research sites across the USA, the UK, Canada, China, Czech Republic, Denmark, France, Germany, Italy, Japan, South Korea, Poland, Russia, Spain, Sweden, and Taiwan. Adults aged 1880 years with a 1-year or longer history of chronic migraine were randomly assigned (1:1:1) to receive oral atogepant 30 mg twice a day, oral atogepant 60 mg once a day, or placebo. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) across the 12-week treatment period. The primary analysis was done in the modified intent-to-treat population and included all randomly assigned participants who received at least one dose of study intervention, had an evaluable baseline period of electronic diary (eDiary) data, and had at least one evaluable post-baseline 4-week period (weeks 1–4, 5–8, and 9–12) of eDiary data during the double-blind period. The safety population consisted of all participants who received at least one dose of study intervention. This trial is registered with ClinicalTrials.gov (NCT03855137).
Findings
Between March 11, 2019 and Jan 20, 2022, 1489 participants were assessed for eligibility. 711 were excluded, and 778 participants were randomly assigned to atogepant 30 mg twice a day (n=257), atogepant 60 mg once a day (n=262), or placebo (n=259). Participants in the safety population were aged 18–74 years (mean 42·1 years). 459 (59%) of 773 patients were White, 677 (88%) patients were female, and 96 (12%) were male. 84 participants discontinued treatment during the trial, and 755 comprised the modified intent-to-treat population (atogepant 30 mg twice a day n=253, atogepant 60 mg once a day n=256, and placebo n=246). Baseline mean number of MMDs were 18·6 (SE 5·1) with atogepant 30 mg twice a day, 19·2 (5·3) with atogepant 60 mg once a day, and 18·9 (4·8) with placebo. Change from baseline in mean MMDs across 12 weeks was 7·5 (SE 0·4) with atogepant 30 mg twice a day, 6·9 (0·4) with atogepant 60 mg once a day, and 5·1 (0·4) with placebo. Least squares mean difference from placebo was 2·4 with atogepant 30 mg twice a day (95% CI 3·5 to 1·3; adjusted p<0·0001) and 1·8 with atogepant 60 mg once a day (2·9 to 0·8; adjusted p=0·0009). Most common adverse events for atogepant were constipation (30 mg twice a day 28 [10·9%]; 60 mg once a day 26 [10%]; and placebo 8 [3%]) and nausea (30 mg twice a day 20 [8%]; 60 mg once a day 25 [10%]; and placebo 9 [4%]). Potentially clinically significant weight decrease (≥7% reduction at any time post-baseline) was observed in each treatment group (atogepant 30 mg twice a day 14 [6%]; atogepant 60 mg once a day 15 [6%]; and placebo 3 [2%]).
Interpretation
Atogepant 30 mg twice a day and 60 mg once a day showed clinically relevant reductions in MMDs across 12 weeks in chronic migraine patients. Both atogepant doses were well tolerated, consistent with the known safety profile of atogepant.
DOI: 10.1016/S0140-6736(23)01049-8
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01049-8/fulltext
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