ImportancePatients 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.ObjectiveTo 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 ParticipantsThe 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.InterventionsPatients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent).Main Outcomes and MeasuresThe 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.ResultsA 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.Conclusions and RelevanceResults 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.Trial RegistrationClinicalTrials.gov Identifier: NCT03927144

中文翻译：

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早期使用 Erenumab 与非特异性口服偏头痛预防药

重要性偏头痛患者经常因耐受性差和/或疗效不足而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。目的比较erenumab和非特异性口服偏头痛预防药物之间的疗效、耐受性、患者依从性和患者满意度。 OMPM）适用于先前 1 或 2 种预防性治疗失败的阵发性偏头痛 (EM) 患者。设计、设置和参与者为期 12 个月的前瞻性、介入性、全球性、多中心、主动对照、随机临床试验，比较 2 种治疗的持续益处成人发作性偏头痛患者的范例（erenumab qm 与口服预防药）（APPRAISE）试验是一项为期 12 个月的开放标签、多中心、主动对照、4 期随机临床试验，于 2019 年 5 月 15 日至 2021 年 10 月 1 日进行。这项务实的试验在 17 个国家的 84 个中心进行。总体而言，参与者年龄为 18 岁或以上，有 12 个月或更长的偏头痛病史，每月偏头痛天数 (MMD) 为 4 或更多但少于 15。 干预措施 患者被随机 (2:1) 接受 erenumab 或 OMPM 治疗。允许剂量调整（标签相关）。主要结果和措施主要终点是完成 1 年初始指定治疗并在第 12 个月时 MMD 较基线降低 50% 或更多的患者比例。次要终点包括治疗期间 MMD 相对于基线的累积平均变化，以及根据第 12 个月时接受初始指定治疗的患者总体印象变化 (PGIC) 量表得出的反应者比例。结果 总共筛选了 866 名患者，其中其中 245 人未能通过筛查，621 人完成了筛查和基线期。在 621 名随机患者中（平均 [SD] 年龄，41.3 [11.2] 岁；545 名女性 [87.8%]；erenumab 组 413 名 [66.5%]；OMPM 组 208 名 [33.5%]），523 名（84.2%） ）完成了治疗阶段，98 人（15.8%）停止了研究。在第 12 个月时，与 OMPM 相比，分配至 erenumab 组的患者明显更多达到主要终点（413 例中的 232 例 [56.2%] vs 208 例中的 35 例 [16.8%]；比值比 [OR]，6.48；95% CI，4.28-9.82；磷<.001)。与 OMPM 相比，erenumab 治疗显示出更高的应答率（413 例中的 314 例 [76.0%] vs 208 例中的 39 例 [18.8%]；OR，13.75；95% CI，9.08-20.83；磷<.001）在 PGIC 量表上（第 12 个月时≥5）。据报道，erenumab 治疗与 OMPM 治疗相比，累积平均 MMD 显着降低（-4.32 与 -2.65；治疗差异 [SE]：-1.67 [0.35] 天；磷< .001）。与 OMPM 组相比，erenumab 组中更换药物的患者明显较少（413 例中的 9 例 [2.2%] vs 208 例中的 72 例 [34.6%]）并因不良事件而停止治疗（408 例中的 12 例 [2.9%] vs 206 例中的 48 例） [23.3%]）。没有发现新的安全信号。结论和相关性这项随机临床试验的结果表明，对于先前 1 或 2 次预防性治疗失败的 EM 患者，早期使用 erenumab 比连续 OMPM 提供了更大且持续的疗效、安全性和依从性。试验注册临床试验。政府标识符：NCT03927144