Saigoh Kazumasa, Takeshima Takao, Nakai Masami, Shibasaki Yoshiyuki, Ishida Miki, Ning Xiaoping, Barash Steve, Isogai Yuki, Koga Nobuyuki
Department of Neurology, Kindai University School of Medicine, Osaka, Japan.
Headache Center, Department of Neurology, Tominaga Hospital, Osaka, Japan.
J Pain Res. 2023 Apr 20;16:1311-1319. doi: 10.2147/JPR.S393854. eCollection 2023.
Fremanezumab monoclonal antibody therapy has demonstrated efficacy for chronic migraine (CM) with rapid onset and good tolerability. This subgroup analysis of two clinical trials (Japanese and Korean CM Phase 2b/3 [NCT03303079] and HALO CM Phase 3 [NCT02621931]) aimed to evaluate the efficacy and safety of fremanezumab in Japanese patients.
Both trials randomly assigned eligible patients at baseline (1:1:1 ratio) to subcutaneous monthly fremanezumab, quarterly fremanezumab, or placebo at 4-week intervals. The primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12-week period after the first dose of study medication (analyzed by ANCOVA over 12 weeks and MMRM over initial 4 weeks). Secondary endpoints examined other aspects of efficacy, including medication use and disability.
A total of 479 and 109 patients were Japanese in the Japanese and Korean CM Phase 2b/3 and HALO CM trials, respectively. Baseline and treatment characteristics were generally similar between treatment groups for both trials. Results of subgroup analyses for the primary endpoint according to ANCOVA demonstrated the superiority of fremanezumab over placebo in Japanese patients (quarterly fremanezumab, p=0.0005; monthly fremanezumab, p=0.0002 in both trials). Results using the MMRM analysis confirmed the rapid onset of action in this population. Results of the secondary endpoints further supported the efficacy of fremanezumab in Japanese patients. Fremanezumab was well tolerated with nasopharyngitis and injection-site reactions representing the most common adverse events in all treatment groups.
Despite the limitations of subgroup analyses, these consistent results confirm the efficacy and tolerability of fremanezumab in Japanese patients with CM.
孚来美单克隆抗体疗法已被证明对慢性偏头痛（CM）有效，起效迅速且耐受性良好。这项对两项临床试验（日本和韩国CM 2b/3期[NCT03303079]和HALO CM 3期[NCT02621931]）的亚组分析旨在评估孚来美在日本患者中的疗效和安全性。
两项试验均在基线时将符合条件的患者以1:1:1的比例随机分配，分别接受每月一次皮下注射孚来美、每季度一次皮下注射孚来美或安慰剂，给药间隔为4周。主要终点是在首次服用研究药物后的12周内，每月（28天）至少中度严重程度头痛天数从基线的平均变化（通过12周的协方差分析和最初4周的混合效应重复测量模型分析）。次要终点考察了疗效的其他方面，包括药物使用情况和功能障碍。
在日本和韩国CM 2b/3期试验以及HALO CM试验中，分别有479名和109名患者为日本人。两项试验中各治疗组的基线和治疗特征总体相似。根据协方差分析对主要终点进行的亚组分析结果显示，在日本患者中孚来美优于安慰剂（两项试验中，每季度一次皮下注射孚来美，p = 0.0005；每月一次皮下注射孚来美，p = 0.0002）。使用混合效应重复测量模型分析的结果证实了该人群中孚来美的快速起效。次要终点的结果进一步支持了孚来美在日本患者中的疗效。孚来美耐受性良好，鼻咽炎和注射部位反应是所有治疗组中最常见的不良事件。
尽管亚组分析存在局限性，但这些一致的结果证实了孚来美在日本CM患者中的疗效和耐受性。
