CGRP and migraine

Journal of Neurology, Jan 2016

M. Cauchi, N. P. Robertson

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://link.springer.com/content/pdf/10.1007%2Fs00415-015-8000-4.pdf

CGRP and migraine

J Neurol CGRP and migraine M. Cauchi 0 1 N. P. Robertson 0 1 0 Department of Neurology, Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University , Cardiff , UK 1 & N. P. Robertson - Migraine has been estimated to be the seventh highest cause of disability worldwide, and the third most common disease worldwide after dental caries and tension type headache. However, the use of currently available acute and prophylactic medications to control this condition, such as 5-HT1 agonists (triptans) and beta-blockers, is limited by side effects and efficacy so that alternative and more specific treatments are required. More recently, an improved understanding of the pathophysiology of disease has allowed investigation of new therapeutic targets. The 37 amino acid neuropeptide calcitonin gene-related peptide (CGRP) has been shown to play a crucial role in the trigeminocervical complex pathway for nociception in the head. Studies have demonstrated elevated levels in the external jugular vein during the headache phase of migraine, with reduction following headache resolution. Furthermore, CGRP infusion triggers migraine type headache and subsequent treatment with triptans results in normalization of CGRP levels. This neuropeptide is therefore thought to have a central role in pain modulation as it participates in the neurovascular pathway and contributes to the vasodilation and neurogenic inflammation, which leads to migrainous attacks. Targeting CGRP may provide the ideal therapeutic tool needed for control of this common and debilitating illness. The three studies chosen for this month’s journal club are a small sample of the large amount of research being performed on CGRP. The first investigates whether its measurement can be used to classify migraine. The second and third articles are phase II clinical trials which investigate the use of CGRP antagonists and a monoclonal antibody CGRP. Interictal increase in CGRP levels in peripheral blood as a biological marker for chronic migraine In this study, the authors investigated the possible use of CGRP as a marker for chronic migraine. 103 female patients diagnosed with chronic migraine according to international headache society criteria were recruited. Cases reported an average of 9.5 ± 3.4 years of chronic migraine and attempted detoxification at least once for a minimum of 2 months if diagnosed with analgesic overuse migraine. The control groups consisted of 31 healthy women with no headaches and on no medications, 43 females with episodic migraine, and 14 patients with cluster headaches (13 female, 1 male). Morning blood samples were taken from all patients on days without moderate/severe headaches. No symptomatic medications were allowed in the previous 24 h and prophylactic medications were continued. CGRP was found to be significantly higher in chronic migraine as compared to all control groups interictally. The authors subsequently analyzed the potential of CGRP as a biomarker for chronic migraine and concluded that for a CGRP concentration of 43.45 ng/ml, 90.38 % of CM, and 80.64 % of controls would be correctly classified. They also propose that it is possible to distinguish between chronic migraine and episodic migraine on the CGRP level alone. Comment. Although these findings demonstrate considerable potential for CGRP levels as a disease biomarker, considerably more evidence is required before it could be used in clinical practice. Sensitivity and specificity remains poor, and its value in the clinical setting remains unclear particularly as the IHS guidelines appear to provide clear guidance for the clinician. Furthermore, the choice of control groups is limited and it would be of interest to extend these groups to include cases more representative of general clinical practice. However, the study underlines the relevance of CGRP in pathophysiology and holds promise as an objective measure of response and of treatment stratification for future therapeutic trials and also those trials specifically targeting this molecule. Cernuda-Morollo´n V et al (2013) Neurology 81:1191–1196. BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial Previous studies of CGRP antagonists have been limited by early termination due to liver toxicity. This well-designed, single-dose, double-blind, randomized, multicenter evaluation of the CGRP antagonist BMS-927711 measures efficacy as an acute migraine therapy. 1026 patients were enrolled and 885 randomized to receive a single dose of placebo, 100 mg sumatriptan, or one of 6 different doses of BMS-927711 (10, 25, 75, 150, 300 or 600 mg). Exclusion criteria included a history of vascular disease and the concomitant use of drugs metabolized by CYP3A. Prophylactic migraine therapy was allowed but the use of other acute therapies was prohibited 2 days prior to randomization. A Bayesian analysis of the observed response rates allocated group (...truncated)


This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1007%2Fs00415-015-8000-4.pdf

M. Cauchi, N. P. Robertson. CGRP and migraine, Journal of Neurology, 2016, pp. 192-194, Volume 263, Issue 1, DOI: 10.1007/s00415-015-8000-4