Eli Lilly and Company, Indianapolis, Indiana, USA.
, Avenida de la Industria 30, 28108, Alcobendas, Madrid, Spain.
J Headache Pain. 2022 Jul 6;23(1):76. doi: 10.1186/s10194-022-01440-w.
In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA).
Data included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II-IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings.
Across 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9-45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant.
The efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words.
由于缺乏头对头试验，因此缺乏新型药物治疗偏头痛急性发作的疗效起始时间的综合证据。本研究旨在通过网络荟萃分析（NMA）探索拉米替坦（血清素[5-羟色胺] 1F 受体激动剂）与利马曲班和ubrogepant（降钙素基因相关肽拮抗剂）在偏头痛急性口服治疗中的相对疗效。
NMA 中纳入的数据是通过对 2018 年 4 月（更新于 2020 年 5 月/12 月）进行的慢性/发作性偏头痛伴有/不伴有先兆的成人的 II 期至 IV 期随机对照试验（RCT）的系统文献检索确定的。治疗方法包括：拉米替坦 50、100、200 mg；利马曲班 75 mg；ubrogepant 25、50、100 mg。通过适当情况下按基线风险进行调整的贝叶斯固定效应/随机效应 NMA 进行了两两治疗比较。比较以优势比和 95%可信区间报告。早期疗效终点包括：治疗 2 小时后无痛和治疗 1 小时和 2 小时后疼痛缓解。总结了药物不良反应（ADR）概况。探讨了网络中的异质性和不一致性；进行了敏感性分析以检验结果的稳健性。
在纳入的 12 项 RCT 中，女性占纳入患者的>80%（平均年龄 37.9-45.7 岁）。与利马曲班 75 mg 和 ubrogepant 25 和 50 mg 相比，拉米替坦 100 和 200 mg 达到治疗 2 小时后无痛和疼痛缓解的优势比更高。治疗 1 小时后疼痛缓解的结果与治疗 2 小时后的结果一致，但可比较的比较较少。拉米替坦 50 mg 与 ubrogepant 或 rimegepant 相比，任何结局均无统计学差异。敏感性分析的方向与基础分析一致。最常见报告的不良反应（发生率≥2%）是：拉米替坦为头晕、疲劳、感觉异常、镇静、恶心/呕吐和肌肉无力；利马曲班为恶心；ubrogepant 为恶心、嗜睡和口干。
这项间接比较的疗效结果表明，拉米替坦 100 mg 或 200 mg 可能是偏头痛患者寻求快速起效的急性治疗选择。与利马曲班和 ubrogepant 不同，拉米替坦的使用主要与神经系统事件相关，这些事件大多为轻度或中度，且具有自限性。350/350 字。
