Assessment of Erenumab Safety and Efficacy in Patients With Migraine With and Without Aura: A Secondary Analysis of Randomized Clinical Trials

Abstract

Importance: Migraine with aura may respond differently to therapies than migraine without aura. Individuals with migraine with aura have an elevated vascular risk, necessitating a safety assessment of migraine preventive treatments in this patient subgroup.

Objective: To assess the efficacy and safety profiles of erenumab in patients with migraine with aura.

Design, setting, and participants: This post hoc secondary analysis evaluated 4 double-blind, placebo-controlled randomized clinical trials that were conducted in treatment centers in North America, Europe, Russia, and Turkey between August 6, 2013, and November 12, 2019. Participants were adults aged 18 to 65 years with episodic migraine or chronic migraine and were randomized to receive either erenumab or placebo.

Interventions: One or more dose of erenumab (70 mg or 140 mg once per month) or placebo was administered by subcutaneous injection in the double-blind treatment phase and open-label or dose-blinded active treatment, and erenumab, 70 mg or 140 mg, was administered once per month by subcutaneous injection during extension phases.

Main outcomes and measures: Efficacy assessments included change from baseline monthly migraine days (MMDs) and monthly acute migraine-specific medication (AMSM) days. Safety end points included patient incidences of adverse events. Subgroups of patients were categorized according to their history of aura.

Results: Of the 2682 patients who were randomized in the 4 trials, 1400 (52.2%) received 1 or more dose of erenumab, 70 mg or 140 mg, and 1043 (38.9%) received placebo. Patients had a mean (SD) age of 41.7 (11.2) years and were predominantly women (n = 2055 [84.1%]). Reductions from baseline MMDs and AMSM days were greater in the erenumab than placebo groups in patients with and without a history of aura during the double-blind treatment phase, and these reductions were maintained throughout the extension phases. In patients with episodic migraine and a history of aura, least-squares mean differences in change from baseline MMDs at week 12 were -1.1 (95% CI, -1.7 to -0.6) in those who received erenumab, 70 mg, and -0.9 (95% CI, -1.6 to -0.2) in those who received erenumab, 140 mg, compared with placebo. In patients with chronic migraine with a history of aura, the least-squares mean differences from placebo treatment were -2.1 (95% CI, -3.8 to -0.5) in those who received erenumab, 70 mg, and -3.1 (95% CI, -4.8 to -1.4) in those who received erenumab, 140 mg. Overall safety profiles were similar across treatment groups regardless of aura history and were comparable to that of placebo over 12 weeks, with no increased emergence of adverse events over time.

Conclusions and relevance: Results of this secondary analysis of 4 randomized clinical trials showed reduced migraine frequency and AMSM days with erenumab treatment in patients with migraine with and without a history of aura. The findings support the efficacy and safety of using erenumab in this patient population.

Trial registration: ClinicalTrials.gov Identifiers: NCT01952574, NCT02456740, NCT02483585, NTCT02066415, and NCT02174861.

Trial registration: ClinicalTrials.gov NCT02483585 NCT02456740 NCT02174861 NCT01952574 NCT02066415.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Ashina reported being a consultant or scientific advisor for AbbVie, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva Pharmaceuticals; being a principal investigator for ongoing trials for AbbVie/Allergan, Amgen, Eli Lilly, and Novartis; and receiving grants from Lundbeck Foundation, Novo Nordisk Foundation, and Novartis. Dr Goadsby reported receiving consulting fee, speaking or teaching fee, and/or research grants from Akita Biomedical, Alder Biopharmaceuticals, Allergan, Amgen, Autonomic Technologies, Avanir Pharmaceuticals, Cipla Ltd, CoLucid Pharmaceuticals Inc, Dr Reddy's Laboratories, electroCore Inc, Eli Lilly, eNeura Inc, Journal Watch, Massachusetts Medical Society, Medico-Legal Journal, Novartis, Oxford University Press, Pfizer, Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina Inc, UpToDate, and Wolters Kluwer. Dr Dodick reported consulting for Amgen, Atria, Clexio, Cerecin, Cooltech, Ctrl M, Allergan, Biohaven, GSK, Lundbeck, Eli Lilly, Novartis, Impel, Satsuma, Theranica, WL Gore, Nocira, Pieris, Praxis, Revance, Equinox; receiving honoraria from Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Academy for Continued Healthcare Learning, Majallin LLC, Medlogix Communications, MJH Lifesciences, Miller Medical Communications, Southern Headache Society, WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, Cambridge University Press; receiving research support from the US Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, Patient Centered Outcomes Research Institute; owning stock options of Ctrl M, Aural Analytics, ExSano, Palion, Healint, Theranica, Second Opinion/Mobile Health, and Nocira; owning shares or options and serving on the board of Epien, Matterhorn, Ontologics, King-Devick Technologies, and Precon Health; and holding patent 17189376.1-1466:v (Title: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis). Dr Tepper reported receiving research grants (no personal compensation) from Alder, Allergan, Amgen, ATI, Dr. Reddy’s, ElectroCore, eNeura, Neurolief, ScionNeurostim, Teva, and Zosano; consulting for Acorda, Alder, Alexsa, Allergan, Alphasights, Amgen, ATI, Axsome Therapeutics, Biohaven, Charleston Labs, DeepBench, Dr. Reddy’s, ElectroCore, Eli Lilly, eNeura, ExpertConnect, Gerson Lehman Group, Guidepoint Global, GSK, Impel, Magellan Rx Management, Navigant Consulting, Neurolief, Nordic BioTech, Novartis, Pfizer, Reckner Healthcare, Satsuma, ScionNeurostim, Slingshot Insights, Sorrento, Sudler and Hennessey, Supernus, Teva, Theranica, Trinity Partners, XOC, and Zosano; holding stock options of ATI; receiving a salary from the American Headache Society; and receiving royalties from Springer. Dr Xue reported being an employee and stockholder of Amgen Inc during the conduct of the study. Ms Zhang reported being an employee and stockholder of Amgen Inc during the conduct of the study. Dr Brennan reported being an employee and stockholder of Amgen Inc during the conduct of the study. Dr da Silva Lima reported being an employee and stockholder of Amgen Inc during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Study Schema and Patient Flow

aFour hundred sixty-four patients received erenumab, 70 mg, and 276 received erenumab, 140 mg. bFour hundred twenty-nine patients received erenumab, 70 mg, and 231 received erenumab, 140 mg.

Figure 2.. Monthly Migraine Days (MMDs) and Acute Migraine–Specific Medication (AMSM) Days by History of Aura in Episodic Migraine

Error bars represent 95% CIs. LSM indicates least-squares mean.

Figure 3.. Monthly Migraine Days (MMDs) and Acute Migraine–Specific Medication (AMSM) Days by History of Aura in Chronic Migraine

Error bars represent 95% CIs. LSM indicates least-squares mean.

Figure 4.. Incidence Rate of Adverse Events (AEs)

BP indicates blood pressure; CK-MB, creatine kinase MB.