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.

Long-term reductions in disease impact in patients with chronic migraine following preventive treatment with eptinezumab

“…This early efficacy finding is consistent with a previous post hoc analysis of data from PROM-ISE-2, where more patients treated with eptinezumab than those receiving placebo responded as early as month 1 following infusion [21]. Additionally, eptinezumab has been associated with rapid improvements of health-related quality of life, even when administered during a migraine attack, with eptinezumab significantly improving PROs after 4 weeks compared with placebo [22]. The results reported here support and are consistent with previously published results from the double-blind, placebo-controlled PROMISE-2 trial demonstrating that the preventive treatment effect of eptinezumab significantly reduces monthly migraine days from baseline relative to placebo (100 mg, -7.7 days, 300 mg, -8.2 days; placebo, -5.6 days), is sustained over a full 24 weeks, and has an acceptable safety profile in patients with chronic migraine [11,23].…”

Optimization of acute medication use following eptinezumab initiation during a migraine attack: post hoc analysis of the RELIEF study

“…Changes from baseline in HIT-6 total score did not show a clear trend of increasing improvement with poorer baseline optimization; however, eptinezumab treatment was associated with numerically larger improvements than placebo in HIT-6 total score at week 4, similar to the mTOQ-6 [16]. The most pronounced effects were noted in very poorly optimized patients, which may include patients who are potentially stuck in the vicious cycle of medication overuse and MOH.…”

“…However, the design of RELIEF limits the ability to connect the preventive migraine efficacy of eptinezumab to the changes observed on patient-reported outcomes, though it has been shown that the preventive effect of eptinezumab can be observed as early as the day after infusion [28]. These analyses did not exclude patients who did not experience a new migraine during the 4-week treatment period, which occurred more frequently in the eptinezumab group than in the placebo group [16]. The effects of not experiencing another migraine attack in the study may over-or underestimate patient-reported evaluation of acute treatment optimization.…”

“…Eptinezumab also resulted in less use of rescue medication during the attack as compared with placebo [15]. Additionally, when compared to placebo, eptinezumab-treated patients demonstrated greater improvement in acute treatment response during subsequent migraine attacks as measured by the prespecified 6-item Migraine Treatment Optimization Questionnaire (mTOQ-6) total score [16].…”

New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy

“…Eptinezumab is the only intravenous anti-CGRP(-R) mAb. Eptinezumab reaches its maximum serum concentration within minutes to hours, whereas other antibodies require up to one week to reach their maximum levels (74)(75)(76). Notably, in an acute migraine treatment setting, switching between drugs within the same class (e.g., triptans) is an accepted strategy.…”