拉米地坦在日本偏头痛患者中的快速起效和持续疗效：一项随机对照试验的预设分析

Rapid Onset and Sustained Efficacy of Lasmiditan Among Japanese Patients with Migraine: Prespecified Analyses of a Randomized Controlled Trial.

作者信息

Matsumori Yasuhiko, Komori Mika, Tanji Yuka, Ozeki Akichika, Sakai Fumihiko

机构信息

Sendai Headache and Neurology Clinic, Sendai, Japan.

Japan Drug Development and Medical Affairs, Eli Lilly Japan K.K., 5-1-28, Isogamidori, Chuo-ku, Kobe, 651-0086, Japan.

出版信息

Neurol Ther. 2022 Dec;11(4):1721-1734. doi: 10.1007/s40120-022-00403-2. Epub 2022 Sep 22.

DOI:10.1007/s40120-022-00403-2

PMID:36136232

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9588099/

Abstract

INTRODUCTION

Rapid onset and sustained efficacy are important for acute migraine treatment. Global phase 3 trials have demonstrated the early onset and sustained efficacy of the 5-HT receptor agonist lasmiditan. In this prespecified analysis of the MONONOFU study, we assessed the onset and sustained efficacy of lasmiditan in Japanese patients with migraine.

METHODS

MONONOFU was a multicenter, randomized, placebo-controlled, phase 2 study conducted in Japan (May 2019-June 2020). Eligible adults with migraine (N = 846; modified intent-to-treat population, N = 682) were randomized 7:3:7:6 to placebo, lasmiditan 50 mg, 100 mg, or 200 mg, taken orally within 4 h of moderate-to-severe migraine onset. Patients recorded headache severity and symptoms predose and 0.5-48 h postdose. Sustained and modified sustained pain freedom were defined as patients who were headache pain-free 2 h postdose and had no pain (sustained pain freedom) or had mild or no pain (modified sustained pain freedom) at 24 or 48 h without rescue/recurrence medications. Efficacy outcomes were analyzed by logistic regression. Patients also recorded the actual time of pain-free and of meaningful pain relief (Kaplan-Meier analysis).

RESULTS

Compared with placebo, significantly more lasmiditan-treated (100 or 200 mg) patients were headache pain-free, had pain relief, were free of their most bothersome symptom, or had total migraine freedom (no headache or migraine-associated symptoms) within 30-60 min. Median time to pain-free was 9.26, 6.88, 2.75, and 2.30 h in placebo, 50-mg, 100-mg, and 200-mg lasmiditan groups, respectively. Significantly greater proportions of patients treated with 100 (19.7-29.5%) or 200 mg (21.1-35.7%) lasmiditan had sustained or modified sustained pain freedom at 24 or 48 h compared with placebo (10.4-15.8%).

CONCLUSION

This prespecified analysis of data from MONONOFU has confirmed that the efficacy of lasmiditan is rapid in onset and sustained in patients with moderate-to-severe migraine in Japan.

TRIAL REGISTRATION

ClinicalTrials.gov (NCT03962738).

摘要

引言

快速起效和持续疗效对急性偏头痛治疗很重要。全球3期试验已证明5-羟色胺（5-HT）受体激动剂拉米地坦具有起效早和持续疗效的特点。在这项对MONONOFU研究的预先指定分析中，我们评估了拉米地坦在日本偏头痛患者中的起效情况和持续疗效。

方法

MONONOFU是一项于2019年5月至2020年6月在日本进行的多中心、随机、安慰剂对照的2期研究。符合条件的偏头痛成年患者（N = 846；改良意向性治疗人群，N = 682）按7:3:7:6随机分为安慰剂组、50毫克拉米地坦组、100毫克拉米地坦组或200毫克拉米地坦组，在中重度偏头痛发作后4小时内口服。患者记录给药前以及给药后0.5至48小时的头痛严重程度和症状。持续无痛和改良持续无痛的定义为给药后2小时无头痛疼痛且在24或48小时无疼痛（持续无痛）或有轻度疼痛或无疼痛（改良持续无痛）且未使用急救/复发药物的患者。疗效结果通过逻辑回归分析。患者还记录了无痛和有意义的疼痛缓解的实际时间（Kaplan-Meier分析）。

结果

与安慰剂相比，接受拉米地坦治疗（100或200毫克）的患者在30至60分钟内头痛无痛、疼痛缓解、摆脱最困扰症状或完全无偏头痛（无头痛或偏头痛相关症状）的比例显著更高。安慰剂组、50毫克、100毫克和200毫克拉米地坦组的无痛中位时间分别为9.26小时、6.88小时、2.75小时和2.30小时。与安慰剂组（10.4 - 15.8%）相比，接受100毫克（19.7 - 29.5%）或200毫克（21.1 - 35.7%）拉米地坦治疗的患者在24或48小时有持续或改良持续无痛的比例显著更高。