Department of Neurology, Georgetown University Hospital, Washington, DC, USA.
New England Institute for Neurology and Headache, Stamford, CT, USA.
BMC Neurol. 2022 Jun 3;22(1):205. doi: 10.1186/s12883-022-02714-1.
Eptinezumab is an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for the preventive treatment of migraine. In the phase 3 RELIEF study, eptinezumab resulted in shorter time to headache pain freedom and time to absence of most bothersome symptom (MBS; including nausea, photophobia, or phonophobia) compared with placebo when administered during a migraine attack. The objective of this exploratory analysis was to examine the earliest time points that eptinezumab separated from placebo (P < .05) on headache- and migraine-associated symptoms when administered during a migraine attack.
RELIEF, a multicenter, parallel-group, double-blind trial, occurred from November 7, 2019, through July 8, 2020. Adults considered candidates for preventive treatment were randomized to eptinezumab 100 mg (N = 238) or placebo (N = 242) administered intravenously over 30 min within 1-6 h of migraine onset. Outcome measures included headache pain freedom/relief and absence of MBS, patient's choice of photophobia, phonophobia, or nausea, at regular intervals from 0.5 to 48 h after infusion start. Censoring was applied at time of acute rescue medication use.
At hour 1, more eptinezumab-treated patients achieved headache pain freedom (9.7%), headache pain relief (38.7%), and absence of MBS (33.2%) versus placebo (4.1%, 26.9%, and 22.1%, respectively; P < .05 all), with separation from placebo (P < .05) through hour 48. Eptinezumab separated from placebo (P < .05) at hour 1 in absence-of-photophobia (29.4% vs 17.0%) and absence-of-phonophobia (41.2% vs 27.2%) and through hour 48. Initial separation from placebo (P < .05) in absence-of-nausea occurred at end-of-infusion (0.5 h; 36.7% vs 25.4%, respectively).
Preventive treatment with eptinezumab initiated during a migraine attack resulted in more patients achieving headache pain freedom/relief and absence of MBS, with separation from placebo (P < .05) as early as 0.5-1 h following the start of infusion. Rapid resolution of headache- and migraine-associated symptoms by a peripherally acting, intravenously administered antibody suggest a peripheral site of pharmacological action for CGRP blockade.
ClinicalTrials.gov Identifier: NCT04152083 .
依普替扎umab 是一种抗降钙素基因相关肽（CGRP）单克隆抗体，已被批准用于偏头痛的预防性治疗。在 3 期 RELIEF 研究中，与安慰剂相比，依普替扎umab 在偏头痛发作时给药，可缩短头痛缓解至无疼痛的时间和无最困扰症状（MBS；包括恶心、畏光或畏声）的时间。本探索性分析的目的是研究偏头痛发作时依普替扎umab 与安慰剂分离（P<.05）的最早时间点头痛和偏头痛相关症状。
RELIEF 是一项多中心、平行组、双盲试验，于 2019 年 11 月 7 日至 2020 年 7 月 8 日进行。被认为适合预防性治疗的成年人被随机分配至依普替扎umab 100mg（N=238）或安慰剂（N=242），在偏头痛发作后 1-6 小时内静脉输注 30 分钟。主要结局指标包括头痛缓解至无疼痛/缓解和无 MBS，患者选择的畏光、畏声或恶心，从输注开始后 0.5 至 48 小时定期测量。急性解救药物使用时进行删失。
在 1 小时时，与安慰剂相比，更多的依普替扎umab 治疗患者达到头痛缓解（9.7%）、头痛缓解（38.7%）和无 MBS（33.2%）（分别为 4.1%、26.9%和 22.1%；P<.05 均），并在 48 小时内与安慰剂分离（P<.05）。在无畏光（29.4% vs 17.0%）和无畏声（41.2% vs 27.2%）时，依普替扎umab 在 1 小时时与安慰剂分离（P<.05），并在 48 小时内分离。在输注结束时（0.5 小时），与安慰剂（P<.05）相比，最初在无恶心方面的分离发生（分别为 36.7%和 25.4%）。
偏头痛发作时进行预防性治疗，依普替扎umab 可使更多患者达到头痛缓解/缓解和无 MBS，且在输注开始后 0.5-1 小时内与安慰剂分离（P<.05）。外周作用、静脉内给予的抗体可迅速缓解头痛和偏头痛相关症状，提示 CGRP 阻断的药理学作用部位在周围。
ClinicalTrials.gov 标识符：NCT04152083。
