CGRP Antagonists for the Treatment of Chronic Migraines: a Comprehensive Review
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Purpose of Review
The purpose of the following review is to summarize the most recent understanding of migraine pathophysiology, as well as of basic and clinical science pharmacologic literature regarding the development of calcitonin gene receptor peptide (CGRP) antagonists as a novel therapeutic modality for the treatment of migraine headaches. A review is provided of erenumab, the first of its class FDA approved CGRP antagonist.
Despite its high prevalence, the occurrence and treatment of migraine headaches is poorly understood. Erenumab and CGRP antagonists as a whole significantly reduce the average number of migraine days experienced in migraine sufferers.
CGRP antagonists appear to significantly improve treatment outcomes in patients who suffer from episodic and chronic migraines. Erenumab is the first CGRP antagonist to be FDA approved for public use; however, further development of biologics in this class is underway.
KeywordsChronic migraines Episodic migraines Calcitonin gene receptor peptide (CGRP) antagonist Erenumab
Compliance with Ethical Standards
Conflict of Interest
Ivan Urits, Mark R. Jones, Kyle Gress, Karina Charipova, Jacob Fiocchi, and Omar Viswanath declare no conflict of interest. Dr. Kaye is a speaker for Depomed, Inc. and Merck, Inc.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Bajwa ZH, Wootton RJ, Wippold FJ II. Evaluation of headache in adults. UpToDate. 2018.Google Scholar
- 2.Society IH. The International Classification of Headache Disorders, 3rd edn. 2018.Google Scholar
- 3.Cutrer FM, Bajwa ZH. Pathophysiology, clinical manifestations, and diagnosis of migraine in adults. UpToDate. 2017.Google Scholar
- 14.Bajwa ZH, Smith JH. Preventive treatment of migraine in adults. UpToDate. 2018.Google Scholar
- 16.Bajwa ZH, Smith JH. A cute treatment of migraine in adults. UpToDate. 2018.Google Scholar
- 31.Lennerz J, Rühle V, Ceppa E, Neuhuber W, Bunnett N, Grady E, et al. Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: differences between peripheral and central CGRP receptor distribution. J Comp Neurol. 2008;507:1277–99.CrossRefGoogle Scholar
- 32.Russo A, Kuburas A, Kaiser E, Raddant A, Recober A. A potential preclinical migraine model: CGRP-sensitized mice. Mol Cell Pharmocol. 2009;1:264–70.Google Scholar
- 39.Hostetler ED, Joshi AD, Sanabria-Bohorquez S, Fan H, Zeng Z, Purcell M, et al. In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232. J Pharmacol Exp Ther. 2013;347:478–86.CrossRefGoogle Scholar
- 41.Lipton RB, Brennan A, Palmer S, Hatswell AJ, Porter JK, Sapra S, et al. Estimating the clinical effectiveness and value-based price range of erenumab for the prevention of migraine in patients with prior treatment failures: a US societal perspective. J Med Econ. Informa UK Ltd. 2018;21:666–75.CrossRefGoogle Scholar
- 47.de Hoon J, Van Hecken A, Vandermeulen C, Herbots M, Kubo Y, Lee E, et al. Phase I, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers. Cephalalgia. 2018;0:1–11.Google Scholar
- 50.Traynor K. FDA approves licensing of erenumab-aooe to prevent migraine. Am J Heal Pharm. 2018;75:929–30.Google Scholar
- 51.Choy M. Pharmaceutical approval update. Pharm Ther. 2018;43:461–2.Google Scholar
- 52.•• Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16:425–34 Excellent phase 2 randomized controlled trial demonstrating the safety and efficacy of erenumab for the treatment of chronic migraines. CrossRefGoogle Scholar
- 54.• Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. Elsevier Ltd; 2014;13:1100–1107. Excellent phase 2 trial of Eptinezumab for the prevention of frequent episodic migraine. Google Scholar
- 55.• Halker Singh RB, Aycardi E, Bigal ME, Loupe PS, McDonald M, Dodick DW. Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: post-hoc analyses from phase 2 trials. Cephalalgia. 2018;0:1–9 A phase 2 trial of Fremanezumab for the treatment of episodic and chronic migraines. Google Scholar
- 56.• Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR. Evaluation of galcanezumab for the prevention of episodic migraine. JAMA Neurol. 2018;85054. Excellent review of Galcanezumab for the treatment of episodic migraines. Google Scholar