Long-term efficacy and safety of erenumab in migraine prevention: Results from a 5-year, open-label treatment phase of a randomized clinical trial

Abstract

Background and purpose: Although erenumab has demonstrated significant reduction in migraine frequency and improved quality of life in studies lasting 3 to 12 months, little is known about long-term therapy.

Methods: This study was an open-label, 5-year treatment phase following a 12-week, double-blind, placebo-controlled trial in adults with episodic migraine. Patients initially received open-label erenumab 70 mg, which increased to 140 mg following a protocol amendment. Efficacy analyses included change from baseline in monthly migraine days (MMDs), monthly acute migraine-specific medication (AMSM) days, and health-related quality of life.

Results: Of 383 patients enrolled, 250 switched to 140 mg; 215 (56.1%) completed open-label treatment. Mean (standard error) change in MMDs from baseline of 8.7 (0.2) days was -5.3 (0.3) days; an average reduction of 62.3% at year 5. Among patients using AMSM at baseline (6.3 [2.8] treatment days), mean change in monthly AMSM days was -4.4 (0.3) days at the end of 5 years. Patient-reported outcomes indicated stable improvements in disability, headache impact, and migraine-specific quality of life. Exposure-adjusted patient incidence rates of adverse events (AEs) were 123.0/100 patient-years; AEs were most frequently nasopharyngitis, upper respiratory tract infection, and influenza. Serious AEs (SAEs) reported by 49 patients (3.8/100 patient-years) were mostly single occurrence. Two fatal adverse events were reported. There were no increases in incidence of AEs, SAEs, or AEs leading to treatment discontinuation over 5 years of exposure.

Conclusions: Treatment with erenumab was associated with reductions in migraine frequency and improvements in health-related quality of life that were maintained for at least 5 years. No new safety signals were observed.

Trial registration: ClinicalTrials.gov NCT01952574.

Keywords: CGRP receptor; efficacy; headache; headache frequency; monoclonal antibody.

Conflict of interest statement

Messoud Ashina has received personal fees from Alder BioPharmaceuticals, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva Pharmaceuticals. He is currently a principal investigator on clinical trials for Allergan, Amgen, Eli Lilly, Lundbeck, and Novartis. Messoud Ashina has no ownership interest and does not own stocks of any pharmaceutical company. He also serves as an Associate Editor of Cephalalgia, Associate Editor of Headache, and Associate Editor of the Journal of Headache and Pain. Messoud Ashina reports research grants from Lundbeck Foundation, Novo Nordisk Foundation, and Novartis. Peter J. Goadsby reports consulting fees, speaking/teaching fees, and/or research grants from Alder BioPharmaceuticals, Allergan, Amgen, Autonomic Technologies, Celgene, Clexio, electroCore, Eli Lilly, eNeura, Epalex, Impel, Mundipharma, Journal Watch, Massachusetts Medical Society, Medico‐Legal Journal, Novartis, Oxford University Press, Pfizer, Teva Pharmaceuticals, Trigemina, Inc., UpToDate, WL Gore, and Wolters Kluwer. Uwe Reuter reports consulting fees, speaking/teaching fees, and/or research grants from Allergan, Amgen, Autonomic Technologies, CoLucid, electroCore, Novartis, Pharm Allergan, Eli Lilly, and Teva Pharmaceuticals. Stephen Silberstein reports consultant and/or advisory panel member for and/or honoraria from Alder, Allergan, Amgen, Avanir, Dr. Reddy's, eNeura, electroCore Medical, Medscape, Medtronic, Mitsubishi Tanabe Pharma America, NINDS, Supernus, Trigemina, and Teva Pharmaceuticals. David W. Dodick reports the following conflicts within the past 12 months: Consulting: Aeon, Amgen, Clexio, Cerecin, Allergan, Alder, Biohaven, Linpharma, Promius, Eli Lilly, eNeura, Novartis, Impel, Theranica, WL Gore, Nocira, Xoc, Zosano, Upjohn (Division of Pfizer), Pieris, Revance, and Equinox. Honoraria: CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Majallin LLC, MedLogix Communications, Miller Medical Communications, Southern Headache Society (MAHEC), WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, and Cambridge University Press. Research Support: Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, and Patient‐Centered Outcomes Research Institute (PCORI). Stock Options/Shareholder/Patents/Board of Directors: Aural Analytics (options), ExSano (options), Palion (options), Healint (options), Theranica (options), Second Opinion/Mobile Health (options), Epien (options/board), Nocira (options), Ontologics (options/board), King‐Devick Technologies (options/board), Precon Health (options/board). Patent 17189376.1–1466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis. Fei Xue, Feng Zhang, Gabriel Paiva da Silva Lima, Sunfa Cheng, and Daniel D Mikol are employees of and stockholders in Amgen Inc.

© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Figures

FIGURE 1

Study design and patient flow. Patients were treated with placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg every 4 weeks during the 12‐week double‐blind treatment phase. All patient who entered the 5‐year open‐label treatment phase initially received erenumab 70 mg every 4 weeks. aThe dosage was increased to 140 mg following a protocol amendment. bAn additional protocol amendment reinstituted electronic diary data collection for efficacy assessments during years 4 to 5. For year 1, N = number of patients who entered the open‐label treatment phase and had efficacy data available. For years 4 to 5, N = number of patients who received 140 mg erenumab during the open‐label treatment phase and had efficacy data available. OLTP, open‐label treatment phase.

FIGURE 2

Efficacy over time. (a) Change from baseline in monthly migraine days. The mean change from baseline in MMDs is shown for patients enrolled in the parent double‐blind study receiving placebo, erenumab 7 mg, erenumab 21 mg, erenumab 70 mg, and for patients receiving erenumab 70/140 mg in the open‐label treatment phase. Error bars represent SE. Proportions of patients who achieved ≥50%, ≥75%, and 100% reduction from baseline in MMDs (≥50%, ≥75%, and 100% responses) over weeks 253 to 256 are shown. (b) Change from baseline in monthly AMSM days in patients with baseline monthly acute migraine‐specific medication use. The mean change from baseline in monthly AMSM days is shown for patients in the parent double‐blind study receiving placebo, erenumab 7 mg, erenumab 21 mg, and erenumab 70 mg, and for patients receiving erenumab 70/140 mg in the open‐label treatment phase. Error bars represent SE. AMSM, acute migraine‐specific medication; DBTP, double‐blind treatment phase; MMDs, monthly migraine days; OLTP, open‐label treatment phase; SE, standard error.

FIGURE 3

Change in headache impact over time. The mean change from baseline in HIT‐6 total score is shown for patients on placebo, erenumab 7 mg, erenumab 21 mg, and erenumab 70 mg during the double‐blind parent study and for all patients on erenumab 70/140 mg during the OLTP. Error bars represent SE. The proportions of patients who achieved ≥5‐point reduction in HIT‐6 score over weeks 253 to 256 is shown. DBTP, double‐blind treatment phase; HIT‐6, Headache Impact Test; OLTP, open‐label treatment phase; SE, standard error.