Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study

Abstract

Background: Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack.

Methods: RELIEF was a randomized, double-blind, placebo-controlled trial conducted between 2019 and 2020 in adults with ≥1-year history of migraine and 4-15 migraine days per month in the 3 months prior to screening. Patients were randomized (1:1) to a 30-min infusion of eptinezumab 100 mg or placebo within 1-6 h of a qualifying migraine attack onset. The 6-item Headache Impact Test (HIT-6) and 6-item Migraine Treatment Optimization Questionnaire (mTOQ-6) were administered at baseline and week 4, and the Patient Global Impression of Change (PGIC) at week 4. A post hoc analysis of these measures was conducted in patients who reported headache pain freedom at 2 h after infusion start.

Results: Of 480 patients enrolled and treated, 476 completed the study and are included in this analysis. Mean baseline HIT-6 total scores indicated severe headache impact (eptinezumab, 65.1; placebo, 64.8). At week 4, the eptinezumab-treated group demonstrated clinically meaningful improvement in HIT-6 total score compared with placebo (mean change from baseline: eptinezumab, - 8.7; placebo, - 4.5; mean [95% CI] difference from placebo: - 4.2 [- 5.75, - 2.63], P < .0001), with greater reductions in each item score vs placebo (P < .001 all comparisons). Change in HIT-6 total score in the subgroup with 2-h headache pain freedom was - 13.8 for the eptinezumab group compared with - 4.9 for the placebo group. mTOQ-6 total score mean change from baseline favored eptinezumab (change, 2.1) compared with placebo (1.2; mean [95% CI] difference: 0.9 [0.3, 1.5], P < .01). More eptinezumab-treated patients rated PGIC as much or very much improved than placebo patients (59.3% vs 25.9%).

Conclusions: When administered during a migraine attack, eptinezumab significantly improved patient-reported outcomes after 4 weeks compared with placebo, with particularly pronounced effects in patients reporting headache pain freedom at 2 h after infusion start.

Trial registration: ClinicalTrials.gov Identifier: NCT04152083 . November 5, 2019.

Keywords: CGRP; Eptinezumab; MBS; Migraine.

Conflict of interest statement

PM reported receiving personal fees and research support from Abbvie, Amgen/Novartis, Biohaven, Lilly, Lundbeck, and Teva.

PKW reported receiving consulting fees from Abbvie, Amgen, Biohaven, Lilly, Lundbeck, Novartis, Teva; serving on speaker bureaus for Abbvie, Amgen, Biohaven, Lilly, Lundbeck, Novartis, Teva; and receiving research support from Abbvie, Amgen, AZ, Biogen, Lilly, Lundbeck, Novartis, Supernus, Teva.

JA reported receiving clinical trial grants from Abbvie, Biohaven, Lilly, Satsuma, and Zosano; consulting fees from Abbvie, Amgen, Axsome, Biohaven, electroCore, Impel, Lilly, Lundbeck, Revance, Satsuma, Theranica, and Vorso; and speaker fees from Abbvie, Amgen, Biohaven, Impel, Lilly, Lundbeck, and Satsuma.

DCB has received grant support from Amgen, the National Headache Foundation, and the FDA; has received consulting support from Allergan/Abbvie, Amgen, Lilly, Lundbeck, and Teva; and serves on the editorial board of Current Pain and Headache Reports.

RBL receives or has received, as a consultant and/or advisory panel member, honoraria from Lundbeck Seattle BioPharmaceuticals, Allergan, American Academy of Neurology, American Headache Society, Amgen, Biohaven Pharmaceuticals, BioVision, Boston Scientific, Dr. Reddy’s Laboratories, electroCore Medical, eNeura Therapeutics, GlaxoSmithKline, Lilly, Merck, Pernix, Pfizer, Supernus, Teva Pharmaceuticals, Trigemina, Vector, and Vedanta; received compensation from eNeura and Biohaven Pharmaceuticals, has stock or stock options in Biohaven Pharmaceuticals and Manistee; receives research support from Amgen, Migraine Research Foundation, and National Headache Foundation.

GC had nothing to declare.

MKJ, AL, and AE are employees of Lundbeck or one of its subsidiary companies.

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

© 2021. The Author(s).

Figures

Fig. 1

Effects of Eptinezumab vs Placebo on HIT-6–Related Outcomes. A Least Squares (LS) Mean Change From Baseline at Week 4; B Responder Rates at Week 4 for HIT-6 Total Score; C LS Mean Change From Baseline in HIT-6 Item Scores at Week 4; D Responder Rates for HIT-6 Item Scores at Week 4. CI, confidence interval; HIT-6, 6-item Headache Impact Test; LS, least square. *P < .05, **P < .01, ***P < .001 vs placebo. Limited to patients with both baseline and post-baseline HIT-6 data. aFor items 1–3, a responder was defined as a patient with an improvement of ≥1 category; for items 4–6, a responder was defined as a patient with an improvement of ≥2 categories [24]. Error bars represent 95% CI

Fig. 2

Relationship of 2-h Pain Freedom to Change in HIT-6 and Occurrence of Subsequent Migraine. A Mean Change From Baseline to Week 4 in HIT-6 Total Score and B Percent of Patients Without a New Migraine Occurring With or Without Headache Pain Freedom at 2 Hours After Infusion Start. CI, confidence interval; HIT-6, 6-item Headache Impact Test; LS, least square. aLimited to patients with both baseline and post-baseline HIT-6 data Error bars represent 95% CI

Fig. 3

mTOQ-6 Mean Change From Baseline to Week 4. A Mean change from baseline to week 4 in mTOQ-6 total score and B in mTOQ-6 item scores. mTOQ-6, 6-item Migraine Treatment Optimization Questionnaire. aLimited to patients with both baseline and post-baseline mTOQ-6 data. **P < .01, #P = .0053 vs placebo