Mayo Clinic Arizona, Phoenix.
Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853.
Fremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine.
To assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose.
Randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12.
Study participants were aged 18 to 70 years with episodic migraine (6-14 headache days, with at least 4 migraine days, during 28-day pretreatment period). Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded.
Patients were randomized 1:1:1 to receive subcutaneous monthly dosing of fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a single higher dose of fremanezumab, as intended to support a quarterly dose regimen (n = 291; 675 mg of fremanezumab at baseline; placebo at weeks 4 and 8); or placebo (n = 294; at baseline, week 4, and week 8).
The primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose.
Among 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years; 742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group. This resulted in a difference with monthly dosing vs placebo of -1.5 days (95% CI, -2.01 to -0.93 days; P < .001) and with single higher dosing vs placebo of -1.3 days (95% CI, -1.79 to -0.72 days; P < .001). The most common adverse events that led to discontinuation were injection site erythema (n = 3), injection site induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2).
Among patients with episodic migraine in whom multiple medication classes had not previously failed, subcutaneous fremanezumab, compared with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period. Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy.
clinicaltrials.gov Identifier: NCT02629861.
靶向降钙素基因相关肽的完全人源化单克隆抗体依瑞奈佐单抗可能对治疗发作性偏头痛有效。
评估依瑞奈佐单抗每月给药方案或单次高剂量与安慰剂相比预防发作性偏头痛的疗效。
这是一项随机、双盲、安慰剂对照、平行组试验，于 2016 年 3 月 23 日（首位患者随机分组）至 2017 年 4 月 10 日在 9 个国家的 123 个地点进行，包括筛查访视、28 天预处理期、12 周治疗期和第 12 周的最终评估。
研究参与者年龄为 18 至 70 岁，患有发作性偏头痛（28 天预处理期内偏头痛发作 6-14 天，至少 4 天为偏头痛发作）。先前使用 2 类偏头痛预防药物治疗失败的患者被排除在外。
患者以 1:1:1 的比例随机接受皮下每月依瑞奈佐单抗给药（n = 290；基线、第 4 周和第 8 周给予 225 mg；n = 291；给予 675 mg 依瑞奈佐单抗，第 4 周和第 8 周给予安慰剂；n = 294；基线、第 4 周和第 8 周给予安慰剂）。
首次给药后 12 周内每月偏头痛天数的平均变化。
在 875 名随机分组的患者（平均年龄，41.8[SD，12.1]岁；742 名女性[85%]）中，791 名（90.4%）完成了试验。从基线到 12 周，依瑞奈佐单抗每月给药组每月偏头痛天数从 8.9 天减少到 4.9 天，依瑞奈佐单抗单次高剂量组从 9.2 天减少到 5.3 天，安慰剂组从 9.1 天减少到 6.5 天。这导致每月给药组与安慰剂组的差异为-1.5 天（95%CI，-2.01 至-0.93 天；P < .001），单次高剂量组与安慰剂组的差异为-1.3 天（95%CI，-1.79 至-0.72 天；P < .001）。导致停药的最常见不良事件为注射部位红斑（n = 3）、注射部位硬结（n = 2）、腹泻（n = 2）、焦虑（n = 2）和抑郁（n = 2）。
在先前未使用多种药物类别的发作性偏头痛患者中，与安慰剂相比，皮下注射依瑞奈佐单抗在 12 周内每月偏头痛天数平均减少 1.3-1.5 天。需要进一步研究以评估其对其他预防药物的有效性以及在多种预防药物类别的治疗失败的患者中的有效性，并确定长期安全性和疗效。
clinicaltrials.gov 标识符：NCT02629861。
