Patient-reported outcomes, health-related quality of life, and acute medication use in patients with a ≥ 75% response to eptinezumab: subgroup pooled analysis of the PROMISE trials

Abstract

Background: PROMISE-1 and PROMISE-2 evaluated the preventive efficacy, tolerability, and safety of eptinezumab, a calcitonin gene-related peptide-targeted monoclonal antibody, in adults with episodic (EM) and chronic migraine (CM), finding significant reductions in migraine frequency. This post hoc analysis compared patient-reported outcomes (PROs), health-related quality of life (HRQoL) and acute medication use in patients with a ≥ 75% migraine responder rate (MRR) after treatment with eptinezumab to patients with a ≥ 50- < 75% MRR.

Methods: PROMISE-1 and PROMISE-2 were phase 3, randomized, double-blind, placebo-controlled studies. This analysis included patients from both studies treated with eptinezumab 100 mg or 300 mg who experienced ≥ 75% and ≥ 50-< 75% MRR over Weeks 1-12 (wks1-12). In both studies, HRQoL was measured by the 36-item Short-Form Health Survey (SF-36) and acute medication usage. PROMISE-2 also included the 6-item Headache Impact Test (HIT-6), patient-identified most bothersome symptom (PI-MBS), and Patient Global Impression of Change (PGIC).

Results: In PROMISE-1, a total of 115/443 (26.0%; 100 mg, n = 49, 300 mg, n = 66) and 120/443 (27.0%; 100 mg, n = 61, 300 mg, n = 59) eptinezumab-treated patients achieved ≥ 75% and ≥ 50-< 75% MRR over wks1-12, respectively. In PROMISE-2, a total of 211/706 (30.0%; 100 mg, n = 95; 300 mg, n = 116) and 209/706 (29.6%; 100 mg, n = 110, 300 mg, n = 99) eptinezumab-treated patients achieved ≥ 75% and ≥ 50-< 75% MRR over wks1-12, respectively. EM and CM patients with ≥ 75% and ≥ 50-< 75% MRR over wks1-12 showed reduced use of acute headache medication and increased HRQoL to normative levels across SF-36 domains of bodily pain, social functioning, and physical functioning. In CM patients with ≥ 75% and ≥ 50-< 75% MRR over wks1-12, the mean change in HIT-6 total score with eptinezumab (pooled) was - 11.7 and - 7.6, respectively. "Very much" or "much" improvement responses were reported in 41.8% and 16.5% on PI-MBS and 36.2% and 20.0% on PGIC in ≥ 75% and ≥ 50-< 75% MRR, respectively.

Conclusion: Eptinezumab treatment induced a ≥ 75% MRR over wks1-12 in the majority of patients. This patient subgroup reported substantial improvements in PROs associated with headache-related life impact and HRQoL, and reductions in acute headache medication use, which were more marked than those in the ≥ 50-< 75% responders. This study supports the clinical meaningfulness of ≥ 75% MRR for patients with either EM or CM.

Trial registration: ClinicalTrials.gov identifiers: NCT02559895 (PROMISE-1), NCT02974153 (PROMISE-2).

Keywords: CGRP monoclonal antibody; Eptinezumab; Responder analysis.

Conflict of interest statement

RL: 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, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, 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; receives research support from Amgen, Migraine Research Foundation, and National Headache Foundation.

LC: Received personal compensation for serving as a consultant for Alder/Lundbeck, Allergan/AbbVie, Biohaven, Satsuma and Teva; is on the advisory panel for Ctrl M Health (stock); served as an Expert Witness for Vaccine Injury Compensation Program; non-compensated Associated Editor with Headache; non-compensated relationship as Board Member at Large with Alliance for Headache Disorders Advocacy.

CT: Received honoraria for participation in advisory boards for Allergan, electroCore, Eli Lilly, Novartis, and Teva; speaker for Allergan, Eli Lilly, Novartis, and Teva; PI or collaborator in clinical trials sponsored by Alder, Amgen, Eli Lilly, and Teva; received grants from European Commission, the Italian Ministry of Health, and the Italian Ministry of University.

TB: Full-time employee of and stock owner in Lundbeck.

JH: Full-time employee of Pacific Northwest Statistical Consulting, Inc., a contracted service provider of biostatistical resources for Lundbeck.

RC: Full-time employee of Lundbeck or one of its subsidiary companies at the time of the study and manuscript development.

© 2022. The Author(s).

Figures

Fig. 1

Maintenance of treatment response in Weeks 13–24 based on the migraine response rate in Weeks 1–12 in PROMISE-1 and PROMISE-2 (pooled): (A) Percentage of eptinezumab-treated patients maintaining ≥ 75% or ≥ 50–< 75% migraine response during the first infusion (Weeks 1–12) and (B) Percentage of eptinezumab-treated patients maintaining ≥ 50–< 75% migraine response maintaining response in Weeks 13–24

Fig. 2

Number of study months eptinezumab-treated patients maintained same monthly migraine response achieved in Weeks 1–12. Percentage of ≥ 75% migraine responders in (A) PROMISE-1 and (B) PROMISE-2 and percentage of ≥ 50–< 75% migraine responders in (C) PROMISE-1 and (D) PROMISE-2. CM, chronic migraine; EM, episodic migraine; Epti, eptinezumab

Fig. 3

Changes in days of acute headache medication use over Weeks 1–12 in eptinezumab-treated ≥ 75% migraine responders in (A) PROMISE-1 and (B) PROMISE-2 and in ≥ 50–< 75% migraine responders in (C) PROMISE-1 and (D) PROMISE-2. Analyses for each medication are limited to patients who used that medication during the 28-day baseline period. A ≥ 75% or ≥ 50–< 75% migraine responder was defined as a patient who achieved a ≥ 75% or ≥ 50–< 75% reduction in mean monthly migraine days over Weeks 1–12. CM, chronic migraine; EM, episodic migraine; Epti, eptinezumab.

Fig. 4

Responses to HIT-6 item 1 (severe pain) in eptinezumab-treated patients maintaining ≥ 75% migraine response over Weeks 1–12 in PROMISE-2 at (A) baseline and (B) Week 12 and those maintaining ≥ 50–< 75% migraine response over Weeks 1–12 in PROMISE-2 at (C) baseline and (D) Week 12. Item 1 of the 6-item Headache Impact Test (HIT-6) asked “When you have headaches, how often is the pain severe?” A ≥ 75% or ≥ 50–< 75% migraine responder was defined as a patient who achieved a ≥ 75% or ≥ 50–< 75% reduction in mean monthly migraine days over Weeks 1–12. Epti, eptinezumab