Department of Neurology, Headache Outpatient Clinic, Medical University of Innsbruck, Innsbruck, Austria.
Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Headache. 2020 Oct;60(9):2026-2040. doi: 10.1111/head.13929. Epub 2020 Aug 26.
To assess the efficacy of erenumab at the ≥50%, ≥75%, and 100% reduction in monthly migraine days (MMD) response thresholds, using data from the 6-month double-blind treatment phase (DBTP) of the Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention (STRIVE) pivotal clinical trial.
Enrolled patients with episodic migraine (EM; ≥4 MMD and <15 monthly headache days) were randomized (1:1:1) to erenumab 70 mg (n = 312), erenumab 140 mg (n = 318), or placebo (n = 316) once monthly. We determined the proportions of patients with ≥50%, ≥75% and 100% reduction in MMD over the last 3 months of the STRIVE DBTP (months 4 through 6) and conducted post hoc analyses to contextualize the treatment benefit in patient subgroups achieving, and not achieving, these response thresholds. Outcome measures included changes in MMD, acute migraine-specific medication days (MSMD), and patient-reported outcomes.
The proportions of patients with a reduction in MMD from baseline were greater for erenumab than for placebo at all response thresholds. As previously reported for the ≥50% response threshold, 135/312 (43.3%) of patients on erenumab 70 mg and 159/318 (50.0%) on erenumab 140 mg responded, vs 84/316 (26.6%) for placebo. At months 4 through 6, 65/312 (20.8%) and 70/318 (22.0%) of those on erenumab 70 mg and erenumab 140 mg, respectively, achieved ≥75% reductions vs 25/316 (7.9%) on placebo. A reduction of 100% response, which required no migraine days over 3 consecutive months based on observed data, was achieved by 10/312 (3.2%) of patients treated with erenumab 70 mg and 16/318 (5.0%) for erenumab 140 mg, vs 9/316 (2.8%) for placebo. At all response thresholds, responders achieved numerically greater reductions in mean MMD and MSMD, and greater improvements in disability than did the overall population; importantly, these remarkable responses were noted early. Meanwhile, 60/312 (19.2%) and 53/318 (16.7%) patients on erenumab 70 and 140 mg, respectively, had no reduction in MMD from baseline in months 4 through 6, compared with 104/316 (32.9%) patients on placebo.
The responses at the ≥50%, ≥75%, and 100% thresholds provide context for establishing realistic patient and physician expectations regarding the magnitude of treatment benefit that may be achieved by patients with EM responding to erenumab (STRIVE, NCT02456740).
利用 STRIVE 关键性临床试验 6 个月双盲治疗期（DBTP）的数据，评估依瑞奈尤单抗在每月偏头痛天数（MMD）减少≥50%、≥75%和 100%应答阈值的疗效。
入选有发作性偏头痛（EM；≥4 MMD 和＜15 每月头痛天数）的患者，按 1:1:1 的比例随机分为依瑞奈尤单抗 70mg（n=312）、依瑞奈尤单抗 140mg（n=318）或安慰剂（n=316），每月一次。我们确定了在 STRIVE DBTP 的最后 3 个月（第 4 至 6 个月）中，MMD 减少≥50%、≥75%和 100%的患者比例，并进行了事后分析，以了解在达到和未达到这些应答阈值的患者亚组中治疗的获益情况。结局指标包括 MMD、急性偏头痛特异性药物使用天数（MSMD）和患者报告的结局的变化。
与安慰剂相比，依瑞奈尤单抗在所有应答阈值下都能使 MMD 减少的患者比例更高。正如之前报告的≥50%应答阈值一样，依瑞奈尤单抗 70mg 组有 135/312（43.3%）的患者和依瑞奈尤单抗 140mg 组有 159/318（50.0%）的患者达到应答，而安慰剂组有 84/316（26.6%）的患者达到应答。在第 4 至 6 个月时，分别有 65/312（20.8%）和 70/318（22.0%）的依瑞奈尤单抗 70mg 和依瑞奈尤单抗 140mg 组患者达到≥75%的减少，而安慰剂组有 25/316（7.9%）的患者达到。根据观察数据，减少 100%的应答，即连续 3 个月无偏头痛天数，需要 10/312（3.2%）的依瑞奈尤单抗 70mg 治疗患者和 16/318（5.0%）的依瑞奈尤单抗 140mg 治疗患者，而安慰剂组为 9/316（2.8%）。在所有应答阈值下，应答者的平均 MMD 和 MSMD 减少程度以及残疾改善程度均大于总体人群；重要的是，这些显著的反应很早就出现了。同时，与安慰剂组 104/316（32.9%）的患者相比，依瑞奈尤单抗 70mg 组有 60/312（19.2%）和依瑞奈尤单抗 140mg 组有 53/318（16.7%）的患者在第 4 至 6 个月时 MMD 没有从基线减少。
≥50%、≥75%和 100%的应答阈值为确立患者和医生对 EM 患者接受依瑞奈尤单抗治疗可能获得的治疗获益的期望提供了依据（STRIVE，NCT02456740）。
