ImportancePatients with chronic migraine and medication overuse headaches (CM-MOH) represent a particularly burdened subpopulation. This trial provides first, to our knowledge, American Academy of Neurology class I evidence for a preventive therapy in CM-MOH.ObjectiveTo assess erenumab efficacy and safety in patients with nonopioid CM-MOH.Design, Settings, and ParticipantsThis randomized, double-blind, parallel-group, placebo-controlled trial took place at 67 centers in North America, Europe, and Australia from October 7, 2019, to November 2, 2022. This report reflects the primary analysis conducted in January 2023, using a database snapshot from December 1, 2022, which contains the complete dataset of the double-blind treatment period (DBTP). Participants included adults with CM-MOH who had 1 or more preventive treatment failure(s). There were 992 participants screened and 620 participants enrolled (584 in nonopioid cohort and 36 in opioid cohort)InterventionsErenumab, 70 mg, 140 mg, or placebo, once monthly for 24 weeks.Main Outcomes and MeasuresThe primary end point was MOH remission at month 6. Secondary end points included change from baseline in mean monthly acute headache medication days (AHMD) at month 6 and sustained MOH remission throughout the DBTP. Safety end points were adverse events and changes in vital signs.ResultsThe primary analysis population included 584 participants in the nonopioid-treated cohort with a mean age of 44 years and 482 participants were female (82.5%). Baseline demographics and disease characteristics were balanced across groups. At month 6, 134 participants in the erenumab, 140 mg group (69.1%) (odds ratio [OR], 2.01; 95% CI, 1.33-3.05; P < .001 vs placebo) and 117 in the erenumab, 70 mg group (60.3%) (OR, 1.37; 95% CI, 0.92-2.05; P = .13 vs placebo) achieved MOH remission vs 102 participants in the placebo group (52.6%). AHMD use was also reduced in the erenumab groups vs placebo. Least squares mean (standard error) change from baseline in average monthly AHMD was –9.4 (0.4) days in the erenumab, 140 mg group (difference from placebo, –2.7; 95% CI, –3.9 to –1.6; P < .001) and –7.8 (0.4) days in the erenumab, 70 mg group (difference from placebo, –1.2; 95% CI, –2.4 to –0.1; P = .03), vs –6.6 (0.4) days in the placebo group. MOH remission throughout the DBTP was sustained in 119 participants (61.3%,) 96 participants (49.5%), and 73 participants (37.6%) in the erenumab, 140 mg, 70 mg, and placebo groups, respectively. Adverse events were consistent with the known safety profile of erenumab. Treatment-emergent adverse events incidence in the combined erenumab group was 66.8% (259 participants; constipation 15.2% (59 participants) and COVID-19 13.9% (54 participants) were most common.Conclusions and RelevanceIn this study, monthly, 140 mg, erenumab injections safely and effectively achieved MOH remission in patients with nonopioid CM-MOH within 6 months.Trial RegistrationClinicalTrials.gov Identifier: NCT03971071

中文翻译：

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Erenumab 治疗慢性偏头痛非阿片类药物过度使用性头痛的疗效和安全性


重要性慢性偏头痛和药物过度使用性头痛 （CM-MOH） 患者是一个负担特别重的亚群。据我们所知，该试验首先提供了美国神经病学学会 I 类证据，用于 CM-MOH 的预防性治疗。目的评估 erenumab 在非阿片类药物 CM-MOH.Design、设置和参与者患者中的疗效和安全性这项随机、双盲、平行组、安慰剂对照试验于 2019 年 10 月 7 日至 2022 年 11 月 2 日在北美、欧洲和澳大利亚的 67 个中心进行。本报告反映了 2023 年 1 月进行的初步分析，使用了 2022 年 12 月 1 日的数据库快照，其中包含双盲治疗期 （DBTP） 的完整数据集。受试者包括有 1 次或多次预防性治疗失败的 CM-MOH 成人患者。筛选了 992 名参与者，招募了 620 名参与者（非阿片类药物队列 584 名，阿片类药物队列 36 名）干预措施Erenumab，70 毫克、140 毫克或安慰剂，每月一次，持续 24 周。主要结局和测量主要终点是第 6 个月的 MOH 缓解。次要终点包括第 6 个月平均每月急性头痛用药天数 （AHMD） 相对于基线的变化以及整个 DBTP 期间 MOH 的持续缓解。安全终点是不良事件和生命体征的变化。结果主要分析人群包括非阿片类药物治疗队列中的 584 名参与者，平均年龄为 44 岁，其中 482 名参与者为女性 （82.5%）。基线人口统计学和疾病特征在各组之间是平衡的。在第 6 个月时，erenumab 140 mg 组有 134 名参与者 （69.1%） （比值比 [OR]，2.01;95% CI，1.33-3.05;P < .001 与安慰剂相比）和 117 例在 erenumab 中，70 mg 组 （60.3%） （OR，1.37;95% CI，0.92-2。05;P = .13 vs 安慰剂组）达到 MOH 缓解，而安慰剂组有 102 名参与者 （52.6%）。与安慰剂组相比，erenumab 组的 AHMD 使用也有所减少。140 mg 的 erenumab 组平均每月 AHMD 的最小二乘均值（标准误差）相对于基线的变化为 -9.4 （0.4） 天（与安慰剂的差异，-2.7;95% CI，-3.9 至 -1.6;P < .001）和 -7.8 （0.4） 天 （与安慰剂的差异，-1.2;95% CI，-2.4 至 -0.1;P = .03），而安慰剂组为 –6.6 （0.4） 天。在整个 DBTP 中，erenumab、140 mg、70 mg 和安慰剂组分别有 119 名参与者 （61.3%）、96 名参与者 （49.5%） 和 73 名参与者 （37.6%） 维持 MOH 缓解。不良事件与 erenumab 的已知安全性一致。erenumab 联合组治疗中出现的不良事件发生率为 66.8%（259 名参与者;便秘 15.2%（59 名参与者）和 COVID-19 13.9%（54 名参与者）最常见。结论和相关性在本研究中，每月 140 毫克 erenumab 注射安全有效地在 6 个月内实现了非阿片类 CM-MOH 患者的 MOH 缓解。试验注册临床试验。gov 标识符： NCT03971071