目的:描述在日本和韩国进行的前2b/3阶段安慰剂对照试验的探索性终点,特别调查fremanezumab或安慰剂对发作性偏头痛(EM)患者偏头痛相关症状和急性头痛药物使用的影响.
背景:EM与非头痛症状有关,包括恶心,呕吐,畏光,或者恐惧症,这对疾病负担有很大贡献,医疗保健资源利用,生活质量受损。目前的EM治疗包括混合非特异性/偏头痛特异性急性头痛药物,但是药物过度使用会引起头痛和从EM到慢性偏头痛(CM)的进展。在多个阶段2b/3试验中,与安慰剂相比,单克隆抗体fremanezumab显著减少了EM/CM患者每月偏头痛的平均天数.
方法:这是对多中心探索性终点的预设分析,随机化,双盲,安慰剂对照,在日本和韩国EM患者中进行的2b/3期试验(NCT0330303092).患者被随机分配接受fremanezumab,每月或每季度,或匹配的安慰剂,以4周/28天(“每月”)间隔皮下给药,以维持盲检。此处报告的探索性终点是(i)使用任何急性头痛药物,(ii)使用任何偏头痛特异性急性头痛药物,(iii)恶心或呕吐,和(iv)畏光和畏声。
结果:总体而言,357名日本和韩国EM患者每月(n=121)或每季度(n=119)接受fremanezumab或安慰剂(n=117)。与安慰剂相比,每月或每季度服用fremanezumab与超过三个月急性头痛药物使用的平均天数/月相比有显著减少(差异与安慰剂-2.81[95%置信区间(CI)-3.52,-2.11];p<0.001和-2.79[95%CI-3.50,-2.08];p分别<0.001)。在使用偏头痛特异性急性头痛药物的每月平均天数中观察到类似的发现(差异与安慰剂每月和每季度使用Fremanezumab,-2.63[95%CI-3.31,-1.95];p<0.001),恶心或呕吐的平均天数/月(差异与安慰剂-1.09[95%CI-1.60,-0.58];每月Fremanezumab和-1.37的p<0.001[95%CI-1.88,-0.86];季度Fremanezumab的p<0.001),以及畏光和畏声的平均天数(差异与安慰剂-1.22[95%CI-1.80,-0.65];p<0.001和-1.64[95%CI-2.22,-1.06];p分别<0.001)。
结论:在日本和韩国患者中,每月和每季度给予fremanezumab有效预防EM。Fremanezumab还改善了其他疾病方面,包括对急性头痛药物的需求和偏头痛相关症状的频率。
OBJECTIVE: To describe exploratory endpoints from a previous phase 2b/3 placebo-controlled trial conducted in Japan and Korea, specifically investigating the effect of fremanezumab or placebo on migraine-associated symptoms and acute headache medication use in patients with episodic migraine (EM).
BACKGROUND: EM is associated with non-head pain symptoms, including nausea, vomiting, photophobia, or phonophobia, which contribute substantially to the disease burden, healthcare resource utilization, and impaired quality of life. Current EM treatments include a mix of nonspecific/migraine-specific acute headache medications, but medication overuse can induce headaches and progression from EM to chronic migraine (CM). In multiple phase 2b/3 trials, the monoclonal antibody fremanezumab significantly reduced the average number of monthly migraine days experienced by patients with EM/CM compared with placebo.
METHODS: This was a prespecified analysis of exploratory endpoints in a multicenter, randomized, double-blind, placebo-controlled, phase 2b/3 trial conducted in Japanese and Korean patients with EM (NCT03303092). Patients were randomized to receive fremanezumab, either monthly or quarterly, or matching placebo, administered subcutaneously at 4-week/28-day (\"monthly\") intervals to maintain blinding. Exploratory endpoints reported here were the mean change from baseline in the number of days/month with (i) the use of any acute headache medication, (ii) the use of any migraine-specific acute headache medication, (iii) nausea or vomiting, and (iv) photophobia and phonophobia.
RESULTS: Overall, 357 Japanese and Korean patients with EM received either monthly (n = 121) or quarterly (n = 119) fremanezumab or placebo (n = 117). Compared with placebo, fremanezumab administered monthly or quarterly was associated with a significant reduction from baseline in the average number of days/month with acute headache medication use over three months (difference vs. placebo -2.81 [95% confidence interval (CI) -3.52, -2.11]; p < 0.001 and -2.79 [95% CI -3.50, -2.08]; p < 0.001, respectively). Similar findings were observed in the monthly average number of days with migraine-specific acute headache medications (difference vs. placebo with monthly and quarterly fremanezumab, -2.63 [95% CI -3.31, -1.95] for both; p < 0.001), the average number of days/month with nausea or vomiting (difference vs. placebo -1.09 [95% CI -1.60, -0.58]; p < 0.001 for monthly fremanezumab and -1.37 [95% CI -1.88, -0.86]; p < 0.001 for quarterly fremanezumab), and the average number of days with photophobia and phonophobia (difference vs. placebo -1.22 [95% CI -1.80, -0.65]; p < 0.001 and -1.64 [95% CI -2.22, -1.06]; p < 0.001, respectively).
CONCLUSIONS: Monthly and quarterly administered fremanezumab effectively prevented EM in Japanese and Korean patients. Fremanezumab also improved other disease aspects including the need for acute headache medications and the frequency of migraine-associated symptoms.