Tepper Stewart J, Dodick David W, Lanteri-Minet Michel, Dolezil David, Gil-Gouveia Raquel, Lucas Christian, Piasecka-Stryczynska Karolina, Szabó Gyöngyi, Mikol Daniel D, Chehrenama Mahan, Chou Denise E, Yang Yiping, Paiva da Silva Lima Gabriel
The New England Institute for Neurology and Headache, Stamford, Connecticut.
Department of Neurology, Mayo Clinic, Scottsdale, Arizona.
JAMA Neurol. 2024 Sep 16;81(11):1140-9. doi: 10.1001/jamaneurol.2024.3043.
Patients 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.
To assess erenumab efficacy and safety in patients with nonopioid CM-MOH.
DESIGN, SETTINGS, AND PARTICIPANTS: This 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).
Erenumab, 70 mg, 140 mg, or placebo, once monthly for 24 weeks.
The 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.
The 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.
In this study, monthly, 140 mg, erenumab injections safely and effectively achieved MOH remission in patients with nonopioid CM-MOH within 6 months.
ClinicalTrials.gov Identifier: NCT03971071.
慢性偏头痛和药物过度使用性头痛（CM-MOH）患者是负担尤其沉重的亚群体。据我们所知，本试验首次提供了美国神经病学学会I类证据，证明一种针对CM-MOH的预防性疗法。
评估erenumab对非阿片类CM-MOH患者的疗效和安全性。
设计、地点和参与者：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月进行的主要分析，使用的是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。参与者包括有1次或更多次预防性治疗失败的CM-MOH成年患者。共筛选了992名参与者，620名参与者入组（非阿片类队列584名，阿片类队列36名）。
Erenumab，70毫克、140毫克或安慰剂，每月一次，共24周。
主要终点是第6个月时MOH缓解。次要终点包括第6个月时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期间持续的MOH缓解。安全性终点是不良事件和生命体征变化。
主要分析人群包括非阿片类治疗队列中的584名参与者，平均年龄44岁，482名参与者为女性（82.5%）。各组间基线人口统计学和疾病特征均衡。在第6个月时，erenumab 140毫克组的134名参与者（69.1%）（优势比[OR]，2.01；95%置信区间，1.33 - 3.05；与安慰剂相比P < .001）和erenumab 70毫克组的117名参与者（60.3%）（OR，1.37；95%置信区间，0.92 - 2.05；与安慰剂相比P = .13）实现了MOH缓解，而安慰剂组为102名参与者（52.6%）。与安慰剂组相比，erenumab组的AHMD使用也减少。Erenumab 140毫克组平均每月AHMD相对于基线的最小二乘均值（标准误）变化为 -9.4（0.4）天（与安慰剂的差异，-2.7；95%置信区间，-3.9至-1.6；P < .001），erenumab 70毫克组为 -7.8（0.4）天（与安慰剂的差异，-1.2；95%置信区间，-2.4至-0.1；P = .03），而安慰剂组为 -6.6（0.4）天。在erenumab 140毫克组、70毫克组和安慰剂组中，整个DBTP期间持续MOH缓解的参与者分别为119名（61.3%）、96名（49.5%）和73名（37.6%）。不良事件与erenumab已知的安全性特征一致。联合erenumab组中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）最为常见。
在本研究中，每月注射140毫克erenumab可在6个月内安全有效地使非阿片类CM-MOH患者实现MOH缓解。
ClinicalTrials.gov标识符：NCT03971071。
