Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine The ACHIEVE II Randomized Clinical Trial
Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine The ACHIEVE II Randomized Clinical Trial
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DOI：
10.1001/jama.2019.16711
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发表时间：
2019-11-19
影响因子：
120.7
通讯作者：
Trugman, Joel M.
中科院分区：
文献类型：
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作者：
Lipton, Richard B.;Dodick, David W.;Trugman, Joel M.
重要性：Ubrogepant 是一种口服降钙素基因相关肽受体拮抗剂，正在研究用于急性治疗偏头痛。目的：评估 ubrogepant 与安慰剂相比，用于急性治疗单次偏头痛发作的疗效和耐受性。设计、设置和参与者：在美国进行的 3 期、多中心、随机、双盲、安慰剂对照、单次发作临床试验 (ACHIEVE II)（99 项初级保健和研究）诊所；2016年8月26日至2018年2月26日）。参与者是有或没有先兆偏头痛的成年人，每月经历 2 至 8 次偏头痛发作。 干预措施：Ubrogepant 50 mg (n = 562)、ubrogepant 25 mg (n = 561) 或安慰剂 (n = 563)，用于治疗中度或重度疼痛强度的偏头痛。 主要结果和措施：共同主要疗效结果是疼痛消失和参与者指定的大多数患者消失服药 2 小时后出现令人烦恼的偏头痛相关症状（包括畏光、恐声和恶心）。 结果：在 1686 名随机参与者中，1465 名接受了研究治疗（安全人群；平均年龄 41.5 岁；90% 为女性）； 1465 例中的 1355 例（92.5%）可进行疗效评估。 ubrogepant 50 mg 组 464 名参与者中有 101 名 (21.8%) 报告 2 小时疼痛消失，ubrogepant 25 mg 组 435 名参与者中 90 名 (20.7%) 报告，安慰剂组 456 名参与者中 65 名 (14.3%) 报告无疼痛（50 mg 与安慰剂的绝对差异为 7.5%；95% CI， 2.6%-12.5%；P = .01；25 mg 与安慰剂相比，6.4%；95% CI，1.5%-11.5%； ubrogepant 50 mg 组的 463 名参与者中，有 180 名 (38.9%) 报告在 2 小时内没有出现最令人烦恼的相关症状；ubrogepant 25 mg 组的 434 名参与者中，有 148 名参与者 (34.1%) 报告；安慰剂组 456 名参与者中，有 125 名 (27.4%) 报告没有出现最令人烦恼的相关症状（50 mg 组与安慰剂组的绝对差异， 11.5%；95% CI，5.4%-17.5%；P = 0.01；25 mg 与安慰剂相比，6.7%；95% CI，0.6%-12.7%）。任何剂量后48小时内最常见的不良事件是恶心（50毫克，488人中有10人[2.0%]；25毫克，478人中有12人[2.5%]；安慰剂，499人中有10人[2.0%]）和头晕（50毫克，488人中有7人[1.4%]；25毫克，478人中有10人[2.1%]；安慰剂，499 例中的 8 例 [1.6%]）。 结论和相关性：在患有偏头痛的成人中，与安慰剂相比，使用 ubrogepant 进行急性治疗可显着提高 50 mg 和 25 mg 剂量的 2 小时内疼痛缓解率，并且仅使用 50 mg 剂量的 2 小时内没有最令人烦恼的偏头痛相关症状。需要进一步的研究来评估 ubrogepant 相对于其他偏头痛急性治疗的有效性，并评估 ubrogepant 在未经选择的患者群体中的长期安全性。
Importance: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine.Objective: To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack.Design, Setting, and Participants: Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month.Interventions: Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity.Main Outcomes and Measures: Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication.Results: Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P = .01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P = .03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P = .01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P = .07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]).Conclusions and Relevance: Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.