3 个月时行 MIDAS 评分降低能否预测依瑞奈尤单抗治疗结局？一项真实世界、开放标签试验。
Does MIDAS reduction at 3 months predict the outcome of erenumab treatment? A real-world, open-label trial.
机构信息
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, Pavia, Italy.
出版信息
J Headache Pain. 2022 Sep 17;23(1):123. doi: 10.1186/s10194-022-01480-2.
BACKGROUND
In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) score ≥ 11. Eligibility to treatment continuation requires a ≥ 50% MIDAS score reduction at three months (T3). In this study, we evaluate whether a ≥ 50% MIDAS score reduction at T3 is a reliable predictor of response to one-year erenumab treatment.
METHODS
In this prospective, open-label, real-world study, 77 CM patients were treated with erenumab 70-140 mg s.c. every 28 days for one year (T13). We collected the following variables: monthly migraine days (MMDs), monthly headache days (MHDs), days of acute medication intake, MIDAS, HIT-6, anxiety, depression, quality of life and allodynia. Response to erenumab was evaluated as: i) average reduction in MMDs during the 1-year treatment period; and ii) percentage of patients with ≥ 50% reduction in MMDs during the last 4 weeks after the 13 injection (Responders).
RESULTS
Erenumab induced a sustained reduction in MMDs, MHDs and intake of acute medications across the 12-month treatment period, with 64.9% of patients qualifying as Responders. At T3, 55.8% of patients reported a ≥ 50% reduction in MIDAS score (MIDAS) and 55.4% of patients reported a ≥ 50% reduction in MMDs (MMD). MIDAS and MMD patients showed a more pronounced reduction in MMDs during the 1-year treatment as compared to NON-MIDAS (MIDAS: T0: 23.5 ± 4.9 vs. T13: 7.7 ± 6.2; NON- MIDAS: T0: 21.6 ± 5.4 vs. T13: 11.3 ± 8.8, p = 0.045) and NON-MMD (MMD: T0: 23.0 ± 4.5 vs. T13: 6.6 ± 4.8; NON-MMD: T0: 22.3 ± 6.0 vs. T13: 12.7 ± 9.2, p < 0.001) groups. The percentage of Responders did not differ between MIDAS (74.4%) and NON-MIDAS (52.9%) patients (p = 0.058), while the percentage of Responders was higher in the MMD group (83.3%) when compared to NON-MMD (42.9%) (p = 0.001). MMD predicted the long-term outcome according to a multivariate analysis (Exp(B) = 7.128; p = 0.001), while MIDAS did not. Treatment discontinuation based on MIDAS would have early excluded 36.0% of Responders. Discontinuation based on "either MIDAS or MMD" would have excluded a lower percentage (16%) of Responders.
CONCLUSION
MIDAS only partly reflects the 12-month outcome of erenumab treatment in CM, as it excludes more than one third of responders. A criterion based on the alternative consideration of ≥ 50% reduction in MIDAS score or MMDs in the first three months of treatment represents a more precise and inclusive option.
TRIAL REGISTRATION
The trial was retrospectively registered at www.
CLINICALTRIALS
gov (NCT05442008). CGRP: Calcitonin Gene Related Peptide.
MIDAS
MIgraine Disability Assessment. MMDs: monthly migraine days. MIDAS: Patients with a MIDAS score reduction of at least 50% at T3. MMD: Patients with a MMDs reduction of at least 50% at T3. Responder: Patients with a MMDs reduction from baseline of at least 50% in the last 4 weeks of observation period (after 13 erenumab administrations). T0: First erenumab administration. T3, T6, T9, T12: Follow-up visits at three, six, nine, and twelve months after first erenumab administration. T13: Last visit of the protocol.
背景
在意大利，针对 CGRP 通路的单克隆抗体被补贴用于预防治疗高频率和慢性偏头痛（CM），患者的偏头痛残疾评估（MIDAS）得分为≥11。继续治疗的资格要求在三个月（T3）时 MIDAS 评分至少降低 50%。在这项研究中，我们评估了 T3 时 MIDAS 评分降低 50%是否是对依那西普治疗一年反应的可靠预测指标。
方法
在这项前瞻性、开放标签、真实世界研究中，77 例 CM 患者接受依那西普 70-140mg sc，每 28 天一次，共治疗 1 年（T13）。我们收集了以下变量：每月偏头痛天数（MMDs）、每月头痛天数（MHDs）、急性药物摄入天数、MIDAS、HIT-6、焦虑、抑郁、生活质量和感觉异常。对依那西普的反应评估为：i）在 1 年治疗期间 MMDs 的平均减少量；ii）最后 4 周内 MMDs 减少≥50%的患者比例（应答者）。
结果
依那西普在 12 个月的治疗期间持续降低 MMDs、MHDs 和急性药物的摄入，64.9%的患者符合应答者标准。在 T3 时，55.8%的患者报告 MIDAS 评分降低≥50%（MIDAS），55.4%的患者报告 MMDs 降低≥50%（MMD）。与非 MIDAS 组相比，MIDAS 和 MMD 患者在 1 年治疗期间 MMDs 减少更明显（MIDAS：T0：23.5±4.9 vs. T13：7.7±6.2；非 MIDAS：T0：21.6±5.4 vs. T13：11.3±8.8，p=0.045）和非 MMD 组（MMD：T0：23.0±4.5 vs. T13：6.6±4.8；非 MMD：T0：22.3±6.0 vs. T13：12.7±9.2，p<0.001）。在 MIDAS（74.4%）和非 MIDAS（52.9%）患者中，应答者的比例没有差异（p=0.058），而在 MMD 组（83.3%）中，应答者的比例高于非 MMD 组（42.9%）（p=0.001）。多变量分析显示 MMD 预测长期结果（Exp（B）=7.128；p=0.001），而 MIDAS 则没有。基于 MIDAS 的治疗中断将排除 36.0%的应答者。基于“MIDAS 或 MMD 任一项”的治疗中断将排除较低比例（16%）的应答者。
结论
MIDAS 仅部分反映依那西普治疗 CM 的 12 个月结果，因为它排除了三分之一以上的应答者。基于 T3 时 MIDAS 评分或 MMDs 降低≥50%的替代考虑的标准代表了更精确和包容性的选择。
试验注册
该试验在 www.clinicaltrials.gov 上进行了回顾性注册（NCT05442008）。CGRP：降钙素基因相关肽。MIDAS：偏头痛残疾评估。MMDs：每月偏头痛天数。MIDAS：T3 时 MIDAS 评分降低至少 50%的患者。MMD：T3 时 MMDs 降低至少 50%的患者。应答者：最后 4 周观察期（依那西普 13 次给药后）MMD 降低至少 50%的患者。T0：第一次依那西普给药。T3、T6、T9、T12：第一次依那西普给药后 3、6、9 和 12 个月的随访。T13：方案的最后一次就诊。
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