Rapid Onset of Effect of Galcanezumab for the Prevention of Episodic Migraine: Analysis of the EVOLVE Studies
Rapid Onset of Effect of Galcanezumab for the Prevention of Episodic Migraine: Analysis of the EVOLVE Studies
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DOI：
10.1111/head.13691
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发表时间：
2019-11-11
期刊：
影响因子：
5
通讯作者：
Aurora, Sheena K.
中科院分区：
文献类型：
--
作者：
Detke, Holland C.;Millen, Brian A.;Aurora, Sheena K.
目的评价galcanezumab对发作性偏头痛患者的起效。Galcanezumab是一种结合降钙素基因相关肽的单克隆抗体，适用于偏头痛的预防性治疗。设计/方法主要结局指标的数据分析来自先前发表的2项双盲iii期研究（EVOLVE-1 [N = 858]和EVOLVE-2 [N = 915]），其中成年偏头痛患者随机接受每月皮下注射galcanezumab 120mg（负荷剂量240 mg）或240 mg或安慰剂长达6个月。月起效定义为galcanezumab在每月偏头痛天数（mhd）的平均变化中达到并随后保持优于安慰剂的最早月份。如果发病发生在第1个月，则评估和定义周发病为galcanezumab与安慰剂统计学分离的最早一周，并在该月剩余的几周内保持统计学分离。还分析了起效日、每月和每周起效情况，以确定发生>= mhd数较基线减少50%。结果在两项研究中，每月mhd的基线变化显示galcanezumab与安慰剂在第1个月和随后每个月的差异具有统计学意义（P < 0.001）。对两项研究第一个月的分析表明，在第一周起效，galcanezumab治疗的患者在第一周发生较少mhd的几率显著较高(EVOLVE-1的比值比为2.71 [2.00,3.66]，EVOLVE-2的比值比为2.88 [2.16,3.86]；P < 0.001)和随后的每一周与安慰剂治疗的患者相比(P = 50%，从第1周开始，galcanezumab组与安慰剂组的mhd减少了50%（对于EVOLVE-1， galcanezumab组与安慰剂组50%的患者百分比，54.3%对32.4% [P < 0.001]，对于EVOLVE-2, 59.4%对38.0% [P < 0.001]）。结论注射galcanezumab后第一天快速起效的预防作用在两项研究中均得到证实。
Objective To evaluate onset of effect of galcanezumab in patients with episodic migraine. Background Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide and is indicated for preventive treatment of migraine. Design/Methods Data on the primary outcome measure were analyzed from 2 previously published double-blind, Phase 3 studies (EVOLVE-1 [N = 858] and EVOLVE-2 [N = 915]) wherein adult patients with episodic migraine were randomized to receive monthly subcutaneous injections of galcanezumab 120 mg (with 240-mg loading dose) or 240 mg or placebo for up to 6 months. Monthly onset of effect was defined as the earliest month at which galcanezumab achieved and subsequently maintained statistical superiority to placebo on the mean change from baseline in the number of monthly migraine headache days (MHDs). If onset occurred in Month 1, weekly onset was evaluated and defined as the earliest week at which galcanezumab statistically separated from placebo and maintained statistical separation for remaining weeks in that month. Day of onset of effect was also analyzed, as were monthly and weekly onset, for occurrence of >= 50% reduction from baseline in number of MHDs. Results For both studies, change from baseline in monthly MHDs showed a statistically significant separation of galcanezumab from placebo at Month 1 and each subsequent month (each P < .001). Analysis of the first month for both studies indicated onset of effect in the first week, with galcanezumab-treated patients having significantly higher odds of having fewer MHDs in the first week (odds ratio [95% confidence interval] for EVOLVE-1, 2.71 [2.00, 3.66], and for EVOLVE-2, 2.88 [2.16, 3.86]; both P < .001) and each subsequent week compared with placebo-treated patients (P = 50% reduction in MHDs starting at Week 1 (percentage of patients with 50% response in galcanezumab group vs placebo group for EVOLVE-1, 54.3% vs 32.4% [P < .001], and for EVOLVE-2, 59.4% vs 38.0% [P < .001]). Conclusion Rapid onset of preventive effect on the first day after injection of galcanezumab was confirmed in both studies of episodic migraine.