Eli Lilly and Company, Indianapolis, IN, USA.
Xenoscience, Phoenix, AZ, USA.
BMC Neurol. 2021 Apr 23;21(1):175. doi: 10.1186/s12883-021-02196-7.
Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown.
CONQUER was a 3-month, randomized, double-blind, placebo-controlled, phase 3b study that enrolled patients with episodic or chronic migraine who had 2 to 4 migraine preventive medication category failures in the past 10 years. Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). Post hoc analyses were conducted to determine the efficacy of galcanezumab in patients who had not benefited from six of the most commonly prescribed migraine preventive medications. The mean change from baseline in monthly migraine headache days and ≥ 50 % response rates were assessed over months 1-3. Improvement in Migraine-Specific Questionnaire Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The endpoints were estimated via mixed model with repeated measures.
The most common treatment failures due to inadequate efficacy or safety/tolerability, which at least 20 % of patients reported trying without benefit, included topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and metoprolol. Patients who had not previously benefited from these treatments had a greater mean reduction in monthly migraine headache days across months 1-3 in the galcanezumab group compared to placebo (all p < 0.01). More patients treated with galcanezumab experienced a ≥ 50 % reduction from baseline in monthly migraine headache days across months 1-3 compared to placebo (all p < 0.05). Galcanezumab-treated patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to placebo (all p < 0.01).
In this population, galcanezumab was effective in reducing monthly migraine headache days, improving response rates, and enhancing quality of life in patients who had not previously benefited from topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol due to inadequate efficacy or safety/tolerability.
ClinicalTrials.gov NCT03559257 (CONQUER).
加奈珠单抗是一种降钙素基因相关肽（CGRP）单克隆抗体（mAb），用于偏头痛的预防性治疗。虽然加奈珠单抗已证明在一般对先前预防性药物无反应的患者中有效，但在因疗效不足或安全性/耐受性而对个别常用预防性治疗无获益的患者中，其疗效仍未知。
CONQUER 是一项为期 3 个月、随机、双盲、安慰剂对照、3b 期研究，纳入了有 2 至 4 次偏头痛预防性药物类别失败史的发作性或慢性偏头痛患者，这些患者在过去 10 年内。患者被随机分配 1:1 接受安慰剂（N=230）或加奈珠单抗 120mg/月（240mg 负荷剂量；N=232）。事后分析旨在确定加奈珠单抗在因疗效不足或安全性/耐受性而对六种最常用偏头痛预防性药物均无获益的患者中的疗效。在第 1-3 个月评估每月偏头痛头痛天数和≥50%应答率的基线变化。在第 3 个月评估偏头痛特异性问卷角色功能受限（MSQ-RFR）评分的改善。通过混合模型进行终点评估，其中包括重复测量。
最常见的因疗效不足或安全性/耐受性而导致的治疗失败，至少有 20%的患者报告尝试过但没有获益，包括托吡酯、阿米替林、普萘洛尔、丙戊酸或丙戊酸钠、肉毒杆菌毒素 A 和美托洛尔。与安慰剂组相比，之前未从这些治疗中获益的患者在加奈珠单抗组中在第 1-3 个月期间每月偏头痛头痛天数的平均减少更大（所有 p<0.01）。与安慰剂组相比，更多接受加奈珠单抗治疗的患者在第 1-3 个月期间每月偏头痛头痛天数的下降≥50%（所有 p<0.05）。与安慰剂组相比，接受加奈珠单抗治疗的患者在第 3 个月时 MSQ-RFR 评分的平均改善更大（所有 p<0.01）。
在该人群中，加奈珠单抗可有效减少每月偏头痛头痛天数，提高应答率，并改善因疗效不足或安全性/耐受性而对托吡酯、阿米替林、普萘洛尔、丙戊酸或丙戊酸钠、肉毒杆菌毒素 A 和/或美托洛尔无获益的患者的生活质量。
ClinicalTrials.gov NCT03559257（CONQUER）。
