Shift in diagnostic classification of migraine after initiation of preventive treatment with eptinezumab: post hoc analysis of the PROMISE studies

Abstract

Background: Monthly headache frequency directly correlates with personal/societal burden and impacts severity and preventive treatment decisions. This post hoc analysis identified shifts from higher to lower frequency headache categories over 6 months in patients with migraine participating in the PROMISE clinical trials receiving two eptinezumab doses.

Methods: Headache frequency at baseline and over study months 1-6 was categorized into 4 groups: chronic migraine (CM; ≥ 15 monthly headache days [MHDs]), high-frequency episodic migraine (HFEM; 10-14 MHDs), low-frequency episodic migraine (LFEM; 4-9 MHDs), and ≤ 3 MHDs. Outcomes included the percentage of patients within each MHD category, the percentage of patients improving by ≥ 1 MHD category, and the number of months with reduction of ≥ 1 MHD category. Data from patients who received approved eptinezumab doses (100 mg or 300 mg) or placebo were included.

Results: Mean headache frequency at baseline in PROMISE-1 was 10 MHDs; most patients were classified as having HFEM (48.6%) or LFEM (43.9%). At Month 1, 62/221 (28.1%), 75/222 (33.8%), and 45/222 (20.3%) patients who received eptinezumab 100 mg, 300 mg, and placebo had ≤ 3 MHDs, with 97/221 (43.9%), 108/222 (48.6%), and 84/222 (37.8%), respectively, falling below the diagnostic EM threshold at Month 6. More than one-third (79/221 [35.7%], 83/222 [37.4%], and 68/222 [30.6%] of patients in the eptinezumab 100 mg, 300 mg, and placebo groups, respectively), had 6 months of reduction of ≥ 1 frequency category. At baseline in PROMISE-2, mean headache frequency was 20.5 MHDs. All patients (100%) in the eptinezumab 100 mg and placebo groups had CM, as did 99.4% of patients receiving eptinezumab 300 mg. At Month 1, 209/356 (58.7%), 216/350 (61.7%), and 167/366 (45.6%) patients treated with eptinezumab 100 mg, 300 mg, and placebo had ≤ 14 MHDs, with 240/356 (67.4%), 249/350 (71.1%), and 221/366 (60.4%), respectively, falling below CM threshold at Month 6. Additionally, 153/356 (43.0%), 169/350 (48.3%), and 116/366 (31.7%) patients in the eptinezumab 100 mg, 300 mg, and placebo groups, respectively, had 6 months of reduction of ≥ 1 frequency category.

Conclusion: In the PROMISE studies, episodic and chronic migraine patients treated with eptinezumab were more likely to reduce their headache frequency versus placebo, which directly and in a sustained way improved their diagnostic category classification.

Trial registration: ClinicalTrials.gov Identifier: NCT02559895, NCT02974153.

Keywords: Efficacy; Eptinezumab; Migraine; Prevention.

Conflict of interest statement

PP-R has received honoraria as a consultant and speaker from Allergan/AbbVie, Biohaven, Chiesi, Eli Lilly, Medscape, Lundbeck, Novartis, and Teva Pharmaceuticals. Her research group has received research grants from AGAUR, Allergan/AbbVie, EraNet Migraine Research Foundation, FEDER RIS3CAT, Instituto Investigación Carlos III, International Headache Society, la Caixa foundation, MICINN, Neuron, Novartis, PERIS, and Teva; and has received funding for clinical trials from Alder, Allergan/AbbVie, Amgen, electroCore, Eli Lilly, Lundbeck, Novartis, and Teva. She is the Honorary Secretary of the International Headache Society. She is on the editorial board of Revista de Neurologia. She is an associate editor for Cephalalgia, Headache, Neurologia, and Frontiers of Neurology and an advisory Scientific member of the Editorial Board of The Journal of Headache and Pain. She is a member of the Clinical Trials Guidelines Committee and Scientific Committee of the International Headache Society. She has edited the Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society. She is the founder of www.midolordecabeza.org. PP-R does not own stocks from any pharmaceutical company.

DD has been a consultant for Amgen, Allergan/Abbvie, Atria Health, AYYA Biosciences, Biohaven, CapiThera Ltd., Cerecin, Ceruvia Lifesciences LLC, Cooltech, Ctrl M, Eli Lilly, GSK, Impel, Lundbeck, Nocira, Novartis, Perfood, Pfizer, Praxis, Revance, Satsuma, Theranica, and WL Gore. He has received payment or honoraria from Amgen, Allergan/Abbvie, Biohaven, Cambridge University Press, Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Eli Lilly, Global Access Meetings, KLJ Associates, Lundbeck, Majallin LLC, Medlogix Communications, Miller Medical Communications, MJH Lifesciences, Novartis, Oxford University Press, Pfizer, Vector Psychometric Group, WebMD Health/Medscape, and Wolters Kluwer. He has participated on Data Safety Monitoring or Advisory Boards for Allergan/Abbvie, Academy for Continued Healthcare Learning, Amgen, and Biohaven. He has received research support from American Migraine Foundation, Department of Defense, Henry Jackson Foundation, National Institutes of Health, Patient Centered Outcomes Research Institute (PCORI), and Sperling Foundation. He has a leadership or fiduciary role with American Brain Foundation, American Migraine Foundation, International Headache Society, and Global Patient Advocacy Coalition. He owns stock or stock options in Atria Health, Aural Analytics, AYYA Biosciences, Epien, ExSano, Healint, King-Devick Technologies, Man and Science, Matterhorn, Nocira, Ontologics, Precon Health, Second Opinion/Mobile Health, and Theranica. He holds a patent, 17189376.1–1466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis without fee, and has a patent application submitted, Synaquell (Precon Health). AE is a full-time employee of H. Lundbeck A/S. JH is an employee of Pacific Northwest Statistical Consulting, Inc., a contracted service provider of biostatistical resources for Lundbeck. RC was an employee of Lundbeck at the time of manuscript development.

© 2022. The Author(s).

Figures

Fig. 1

Percentage of patients in each diagnostic category, by month, in A) PROMISE-1 and B) PROMISE-2. MHDs, monthly headache days

Fig. 2

Percentage of patients with reduction of ≥ 1 MHD frequency category in A) PROMISE-1 and B) PROMISE-2. MHDs, monthly headache days

Fig. 3

Cumulative number of months with reduction of ≥ 1 MHD frequency category in A) PROMISE-1 and B) PROMISE-2. MHDs, monthly headache days

Fig. 4

Percentage of patients in each diagnostic category, by month, in the subgroup of patients with MOH diagnosis at baseline in PROMISE-2: A) eptinezumab 100 mg; B) eptinezumab 300 mg; C) placebo. MHDs, monthly headache days; MOH, medication-overuse headache