阿托格潘用于传统口服预防治疗失败的成人发作性偏头痛预防治疗的安全性和有效性(ELEVATE):随机、安慰剂对照、3b 期试验。

IF 46.5 1区 医学 Q1 CLINICAL NEUROLOGY
Lancet Neurology Pub Date : 2024-04-01 Epub Date: 2024-02-13 DOI:10.1016/S1474-4422(24)00025-5
Cristina Tassorelli, Krisztián Nagy, Patricia Pozo-Rosich, Michel Lanteri-Minet, Sara Sacco, Tomáš Nežádal, Hua Guo, Rosa De Abreu Ferreira, Giovanna Forero, Joel M Trugman
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引用次数: 0

摘要

背景:阿托吉潘是一种口服降钙素基因相关肽受体拮抗剂,已被批准用于偏头痛的预防性治疗,但尚未在专门的临床试验中评估其对常规口服预防性偏头痛治疗失败者的疗效和安全性。ELEVATE试验评估了阿托格潘预防性治疗发作性偏头痛的安全性、耐受性和疗效,受试者为2至4类常规口服预防性治疗失败的患者:ELEVATE是一项随机、双盲、安慰剂对照、平行组的3b期试验,在加拿大、捷克共和国、丹麦、法国、德国、匈牙利、意大利、荷兰、波兰、俄罗斯、西班牙、英国和美国的73个地点进行。采用交互式网络响应技术,将曾接受过二至四种偏头痛传统口服治疗失败的发作性偏头痛成人患者(18-80 岁)随机(1:1)分配到每天一次口服阿托吉潘 60 毫克或安慰剂,并根据每月偏头痛基线天数、曾接受过的治疗失败次数和地区进行分层。主要终点是非治疗假设估计人群(OTHE)在12周治疗期内平均每月偏头痛天数与基线相比的变化,该人群包括安全人群(所有接受了≥1个剂量研究干预的参与者)中的参与者,他们在基线期和基线后4周中的一个或多个时期(无论是否接受治疗)都有可评估的数据。主要终点采用重复测量混合模型进行分析,并采用固定序列程序控制多重比较。该试验已在ClinicalTrials.gov(NCT04740827)和EudraCT(2019-003448-58)注册,并已完成。研究结果:2021年3月5日至2022年8月4日期间,共筛选了540名参与者,随机分配了315名,313名参与者(280名[89%]女性,33名[11%]男性,300名[96%]白人)接受了至少一剂研究干预。在由309名参与者组成的OTHE人群中(155名被分配给安慰剂,154名被分配给阿托格潘),安慰剂治疗12周后每月偏头痛天数与基线相比的最小平方均值变化为-1-9(SE 0-4),阿托格潘治疗12周后每月偏头痛天数与基线相比的最小平方均值变化为-4-2(0-4)(最小平方均值差异为-2-4,95% CI为-3-2至-1-5;调整后的P解释):阿托格潘 60 毫克,每天一次,安全、耐受性良好,与安慰剂相比,在 12 周内发作性偏头痛患者每月平均偏头痛天数明显减少,且与临床相关。对于这类难以治疗的人群,阿托格潘可能是一种有效的预防性治疗选择:资金来源:Allergan公司(现为艾伯维公司)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial.

Background: Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed.

Methods: ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18-80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with ClinicalTrials.gov (NCT04740827) and EudraCT (2019-003448-58), and is completed.

Findings: Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were -1·9 (SE 0·4) with placebo and -4·2 (0·4) with atogepant (least squares mean difference -2·4, 95% CI -3·2 to -1·5; adjusted p<0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants (vs four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group vs none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group vs two [1%] in the placebo group.

Interpretation: Atogepant 60 mg once a day was safe, well tolerated, and showed significant and clinically relevant reductions in mean monthly migraine days compared with placebo across 12 weeks in patients with episodic migraine who had previously been failed by two to four classes of conventional oral preventive treatments. Atogepant might be an effective preventive treatment option for patients in this difficult-to-treat population.

Funding: Allergan (now AbbVie).

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来源期刊
Lancet Neurology
Lancet Neurology 医学-临床神经学
CiteScore
58.70
自引率
1.00%
发文量
572
审稿时长
6-12 weeks
期刊介绍: The Lancet Neurology is the world-leading clinical neurology journal. It publishes original research that advocates for change in, or sheds light on, neurological clinical practice. The topics covered include cerebrovascular disease, Alzheimer's disease and other dementias, epilepsy, migraine, neurological infections, movement disorders, multiple sclerosis, neuromuscular disorders, peripheral nerve disorders, pediatric neurology, sleep disorders, and traumatic brain injury. The journal publishes a range of article types, including Articles (including randomized clinical trials and meta-analyses), Review, Rapid Review, Comment, Correspondence, and Personal View. It also publishes Series and Commissions that aim to shape and drive positive change in clinical practice and health policy in areas of need in neurology. The Lancet Neurology is an internationally trusted source of clinical, public health, and global health knowledge. It has an Impact Factor of 48.0, making it the top-ranked clinical neurology journal out of 212 journals worldwide.
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