Rapid resolution of migraine symptoms after initiating the preventive treatment eptinezumab during a migraine attack: results from the randomized RELIEF trial

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT04152083 .

Keywords: CGRP; Eptinezumab; MBS; Migraine.

Conflict of interest statement

JA has received research support from AbbVie, Biohaven, Lilly, Satsuma, and Zosano; consulting fees from AbbVie, Aeon, Amgen, Axsome, Biodelivery Sciences International, Biohaven, GlaxoSmithKline, Impel, Lilly, Lundbeck, Nesos, Satsuma, Teva, and Theranica; and speaker fees from AbbVie, Amgen, Biohaven, Lilly, Lundbeck, and Teva.

PM has received personal fees and research support from AbbVie, Amgen/Novartis, Biohaven, Lilly, Lundbeck, and Teva.

PKW has received consulting fees from AbbVie, Amgen, Biohaven, Lilly, Lundbeck, Novartis, and Teva; served on Speaker bureaus for AbbVie, Amgen, Biohaven, Lilly, Lundbeck, Novartis, and Teva; and received research support from AbbVie, Amgen, AZ, Biogen, Lilly, Lundbeck, Novartis, Supernus, and Teva.

GC has nothing to declare.

MKJ, AL, BS, and AE are full-time employees of H. Lundbeck A/S.

RC was an employee of Lundbeck or one of its subsidiary companies at the time of study and manuscript development.

© 2022. The Author(s).

Figures

Fig. 1

Time Course to Headache Pain Freedom (A), Headache Pain Relief (B), and Absence of MBS (C). *P < 0.05, **P <0 .01, ***P < 0.001 vs placebo in analysis censoring for use of rescue medication. The teal/gray bars represent the percentage of patients achieving headache pain freedom (A), headache pain relief (B), and absence of MBS (C) without rescue medication use prior to the achievement. The white bars represent the percent of patients achieving headache pain freedom (A), headache pain relief (B), and absence of MBS (C) regardless of rescue medication use

Fig. 2

Time Course to Absence of Photophobia (A), Phonophobia (B), and Nausea (C). *P < 0.05, **P < 0.01, ***P < 0.001 vs placebo in analysis censoring for use of rescue medication. Analyses were conducted in patients experiencing the corresponding symptom with their qualifying migraine. The teal/gray bars represent the percentage of patients achieving absence of photophobia (A), phonophobia (B), and nausea (C) without rescue medication use prior to the achievement. The white bars represent the percent of patients achieving absence of photophobia (A), phonophobia (B), and nausea (C) regardless of rescue medication use

Fig. 3

Cumulative Percent of Patients Using Rescue Medication After Start of Infusion. Patients were counted at the first time point of rescue medication use