Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
Headache Center and Clinical Pharmacology Unit, Careggi University Hospital, Florence, Italy.
Cephalalgia. 2024 Nov;44(11):3331024241273968. doi: 10.1177/03331024241273968.
The anti-calcitonin gene-related peptide (CGRP), or its receptor (CGRP/R) monoclonal antibodies (mAbs), offer targeted, effective, and tolerated drugs for migraine. However, about 25% of patients fail to achieve a clinically meaningful response, usually leading to discontinuation. These patients often have a lengthy migraine history and multiple prior preventive treatment failures, resulting in limited therapeutic options. Herein, we describe the cause for and outcome of withdrawal of anti-CGRP/R mAb and evaluate the treatment course until discontinuation.
We conducted a prospective analysis on migraine patients attending the Florence Headache Center in Italy, who discontinued treatment with anti-CGRP/R mAbs. The primary objectives were to describe the reasons for anti-CGRP mAbs discontinuation and the treatment course. Secondary objectives were the evaluation of the absolute change from baseline in monthly headache days, response rates, persistence in medication overuse, absolute change from baseline of the overall number and days of analgesics use per month, change of MIDAS and HIT-6 at three, six, and 12 months, and the last month of treatment.
Among 472 patients, 136 (28.8%) discontinued mAb treatment after an average of 9.0 ± 6.1 (mean ± SD) months. The majority (96/136, 70.6%) discontinued due to ineffectiveness, followed by lost to follow-up during treatment (18/136, 13.1%) and adverse events (10/136, 7.3%). In total, 77.9% of the 136 patients ceased treatment within the first year. Following discontinuation, 48.5% initiated new pharmacological treatment, 39.7% were lost to follow-up, and 11.8% opted not to start another treatment. The majority of patients that started a new pharmacology treatment switched to another anti-CGRP/R (46/68, 67.6%). The second most-used treatment was onabotulinumtoxinA (7/68, 10.2%; all patients in this subgroup were naïve to this treatment), followed by an anticonvulsive medication (7/68, 10.2%). The response status (≥50% reduction in monthly headache days) was achieved by 30.5%, 34.6%, and 40.0% of patients at month 3, 6, and 12 of treatment, respectively. Considering only the comprehensive last month of treatment before withdrawn the percentage of responders was 16.9%.
Although anti-CGRP/R mAbs have provided a substantial amelioration of migraine management, a relevant proportion of patients remains unresponsive and requires additional therapeutic support. Further research is required to identify non-responder features and address unmet needs in migraine treatment.
抗降钙素基因相关肽（CGRP）或其受体（CGRP/R）单克隆抗体（mAbs）为偏头痛提供了靶向、有效且耐受良好的药物。然而，约 25%的患者无法获得临床意义上的缓解，通常导致停药。这些患者通常偏头痛病史较长，且多次预防性治疗失败，导致治疗选择有限。在此，我们描述了停用抗 CGRP/R mAb 的原因和结果，并评估了停药前的治疗过程。
我们对意大利佛罗伦萨头痛中心就诊的偏头痛患者进行了前瞻性分析，这些患者停止了抗 CGRP/R mAb 治疗。主要目的是描述抗 CGRP mAb 停药的原因和治疗过程。次要目的是评估每月头痛天数从基线的绝对变化、反应率、药物过度使用的持续时间、每月整体镇痛药使用次数和天数的从基线的绝对变化、MIDAS 和 HIT-6 在 3、6 和 12 个月时的变化，以及治疗的最后一个月。
在 472 名患者中，136 名（28.8%）在平均 9.0±6.1（平均值±标准差）个月后停止了 mAb 治疗。大多数（96/136，70.6%）因无效而停药，其次是治疗期间失访（18/136，13.1%）和不良反应（10/136，7.3%）。总共，136 名患者中有 77.9%在第一年之内停止了治疗。停药后，48.5%的患者开始了新的药物治疗，39.7%失访，11.8%选择不开始另一种治疗。大多数开始新药物治疗的患者转而使用另一种抗 CGRP/R（46/68，67.6%）。第二种最常用的治疗方法是肉毒杆菌毒素 A（7/68，10.2%；该亚组中的所有患者均对此治疗方法无经验），其次是抗惊厥药物（7/68，10.2%）。治疗第 3、6 和 12 个月时，分别有 30.5%、34.6%和 40.0%的患者达到反应状态（每月头痛天数减少≥50%）。仅考虑治疗前最后一个月的综合情况，应答者的比例为 16.9%。
尽管抗 CGRP/R mAb 已显著改善偏头痛的管理，但仍有相当比例的患者无反应，需要额外的治疗支持。需要进一步研究以确定无反应者的特征并解决偏头痛治疗中的未满足需求。
