Headache and Neurological Pain Research Group, Vall d'Hebron Institute of Research (VHIR), Department of Medicine, Universitat Autònoma de Barcelona, Spain.
Headache Unit, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
JAMA Neurol. 2024 May 1;81(5):461-470. doi: 10.1001/jamaneurol.2024.0368.
Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden.
To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments.
DESIGN, SETTING, AND PARTICIPANTS: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included.
Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent).
The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment.
A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified.
Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM.
ClinicalTrials.gov Identifier: NCT03927144.
由于不耐受和/或疗效不足，偏头痛患者经常循环使用多种非特异性预防药物，导致依从性低和疾病负担增加。
比较依那西普和非特异性口服偏头痛预防药物（OMPM）在先前使用过 1 或 2 种预防治疗的发作性偏头痛（EM）患者中的疗效、耐受性、患者依从性和患者满意度。
设计、设置和参与者：这项为期 12 个月的前瞻性、干预性、全球、多中心、活性对照、随机临床试验（APPRAISE）比较了两种治疗方案（依那西普 qm 与口服预防药物）在先前使用过 1 或 2 种预防治疗的发作性偏头痛患者中的持续疗效，这是一项为期 12 个月的开放标签、多中心、活性对照、第 4 阶段随机临床试验，于 2019 年 5 月 15 日至 2021 年 10 月 1 日进行。这项实用临床试验在 17 个国家的 84 个中心进行。总体而言，纳入了年龄在 18 岁或以上、偏头痛病史 12 个月或更长时间且每月偏头痛天数（MMD）为 4 天或以上但少于 15 天的患者。
患者被随机（2:1）接受依那西普或 OMPM。允许剂量调整（标签依赖）。
完成初始治疗 1 年且在第 12 个月时 MMD 减少 50%或更多的患者比例。次要终点包括治疗期间 MMD 的累积平均变化和根据患者整体变化印象量表（PGIC）在第 12 个月时对初始治疗的患者的反应比例。
共有 866 名患者接受了筛选，其中 245 名患者未通过筛选，621 名患者完成了筛选和基线期。在 621 名随机患者中（平均[标准差]年龄为 41.3[11.2]岁；545 名女性[87.8%]；413 名[66.5%]在依那西普组；208 名[33.5%]在 OMPM 组），523 名（84.2%）完成了治疗阶段，98 名（15.8%）退出了研究。在第 12 个月时，与 OMPM 相比，依那西普组显著更多的患者达到了主要终点（413 名中的 232 名[56.2%] vs 208 名中的 35 名[16.8%]；比值比[OR]，6.48；95%置信区间[CI]，4.28-9.82；P<.001）。与 OMPM 相比，依那西普治疗显示更高的应答率（413 名中的 314 名[76.0%] vs 208 名中的 39 名[18.8%]；OR，13.75；95%置信区间[CI]，9.08-20.83；P<.001）在 PGIC 量表上（12 个月时≥5）。与 OMPM 治疗相比，依那西普治疗显著减少了累积平均 MMD（-4.32 与-2.65；治疗差异[SE]：-1.67[0.35]天；P<.001）。与 OMPM 相比，依那西普组的患者换药（9/413[2.2%]）和因不良反应（12/408[2.9%]）而停止治疗的患者明显更少（72/208[34.6%]）。未发现新的安全信号。
这项随机临床试验的结果表明，在先前使用过 1 或 2 种预防治疗的 EM 患者中更早使用依那西普比连续使用 OMPM 提供了更大和持续的疗效、安全性和依从性。
ClinicalTrials.gov 标识符：NCT03927144。
