Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Viale Pieraccini 6, Florence, Italy.
Headache Center and Clinical Pharmacology Unit, Careggi University Hospital, Florence, Italy.
CNS Drugs. 2023 Feb;37(2):189-202. doi: 10.1007/s40263-022-00983-5. Epub 2023 Jan 19.
OnabotulinumtoxinA (BTX-A) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (anti-CGRP mAbs) are approved drugs for chronic migraine (CM), a difficult-to-treat condition. Optimization of CM patient management by choosing the best options and determining appropriate time for switching or adding concomitant treatments are highly needed.
Evaluate clinical response to anti-CGRP mAbs in patients who switched from BTX-A due to ineffectiveness defined by different cut-offs and assess the retention rate, effectiveness, and safety of both drugs within the first 9 months of treatment.
A monocentric, cohort study, enrolling patients with CM, resistant to several preventive treatments, first treated with BTX-A and then with anti-CGRP mAbs with two observational phases of 9 months preceded by respective baseline. First, the retention rate and effectiveness of both treatments were measured in all patients. A second analysis assessed effectiveness in patients stratified according to <50 or <30% response rate to BTX-A. The absolute change from baseline in monthly headache days (MHDs), response rate, analgesic use, and persistence in medication overuse (MO) at 3, 6, and 9 months of treatment were recorded. Last observation carried forward (LOCF) analyses, including all patients and assuming no further changes after discontinuation, were performed for all outcomes.
Of the 78 enrolled patients (80.8% female, and 89.7% with MO at baseline), 32 (41.0%) received erenumab, 32 (41.0%) galcanezumab, and 14 (18.0%) fremanezumab. Retention rate was 62.2 and 91.0% for BTX-A and 76.9 and 96.2%, for anti-CGRP mAbs at 3 and 9 months of treatment, respectively. At 9 months of treatment, 22.4% of BTX-A patients and 65.0% of anti-CGRP mAbs patients achieved a ≥50% response rate. Anti-CGRP mAbs reduced MHDs, AMN, and AMDs, and decreased the number of MO patients at 9 months. In patients stratified according to <50 or <30% response rate to BTX-A, response rate (≥50% response at 9 months) to anti-CGRP was 62.9 and 57.9%, respectively. LOCF analyses confirmed these findings. No serious adverse events (AEs) were recorded and only two patients discontinued treatment due to AEs.
Difficult-to-treat CM patients who discontinued BTX-A and received anti-CGRP mAbs showed a substantial clinical improvement in migraine-related outcomes. Switching to an anti-CGRP mAb appears to be a viable option in patients with insufficient response after the first 2 cycles with BTX-A. The appropriate variables, cut-offs, and timing to define ineffectiveness and the best time to switch or combine therapies for difficult-to-treat CM need to be investigated further.
肉毒杆菌毒素 A（BTX-A）和抗降钙素基因相关肽（CGRP）单克隆抗体（抗 CGRP mAb）是治疗慢性偏头痛（CM）的获批药物，CM 是一种难以治疗的疾病。通过选择最佳方案并确定转换或添加伴随治疗的适当时间，优化 CM 患者的管理非常重要。
评估因 BTX-A 疗效不佳（根据不同的截止值定义）而转换为抗 CGRP mAb 的患者的临床反应，并评估两种药物在治疗的前 9 个月内的保留率、有效性和安全性。
一项单中心、队列研究，纳入对多种预防性治疗有抵抗的 CM 患者，首先使用 BTX-A 治疗，然后使用抗 CGRP mAb 治疗，每个治疗阶段均有 9 个月的观察期，分别在前两个观察期进行基线测量。首先，测量两种治疗方法的保留率和有效性。第二项分析根据 BTX-A 治疗的反应率<50%或<30%对患者进行分层，评估有效性。记录治疗 3、6 和 9 个月时从基线的每月头痛天数（MHDs）、反应率、镇痛药使用和药物滥用的绝对变化。对所有结局进行最后观察值结转（LOCF）分析，包括所有患者，假设停药后不再发生进一步变化。
在纳入的 78 名患者（80.8%为女性，基线时有 89.7%存在药物滥用）中，32 名（41.0%）接受了依那西普单抗，32 名（41.0%）接受了加奈珠单抗，14 名（18.0%）接受了弗雷马嗪单抗。BTX-A 和抗 CGRP mAb 在治疗 3 和 9 个月时的保留率分别为 62.2%和 91.0%，76.9%和 96.2%。在治疗 9 个月时，BTX-A 患者中有 22.4%，抗 CGRP mAb 患者中有 65.0%达到≥50%的反应率。抗 CGRP mAb 降低了 MHDs、AMN 和 AMD，并减少了药物滥用患者的数量。根据 BTX-A 治疗的反应率<50%或<30%对患者进行分层，抗 CGRP 的反应率（9 个月时≥50%）分别为 62.9%和 57.9%。LOCF 分析证实了这些发现。未记录到严重不良事件（AE），只有两名患者因 AE 而停止治疗。
因 BTX-A 疗效不佳而转换为抗 CGRP mAb 的难治性 CM 患者，在偏头痛相关结局方面有显著的临床改善。在接受 BTX-A 治疗两个周期后反应不足的患者中，转换为抗 CGRP mAb 似乎是一种可行的选择。需要进一步研究确定定义无效的适当变量、截止值和时间，并确定治疗难治性 CM 的最佳转换或联合治疗时间。
