CGRP-targeted drugs for migraine: still many uncertainties

Abstract

The discovery by Goadsby and colleagues 1 Goadsby PJ Edvinsson L Ekman R Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol. 1988; 23: 193-196 Google Scholar that calcitonin-gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine was the most important advance in migraine research in the past 35 years. The mechanism of CGRP in the generation of migraine attacks led to the development of oral gepants for the treatment of acute migraine attacks and the prevention of migraine; monoclonal antibodies against CGRP or the CGRP receptor were developed for migraine prophylaxis. These new compounds have shown efficacy in large placebo-controlled trials. 2 VanderPluym JH Halker Singh RB Urtecho M et al. Acute treatments for episodic migraine in adults: a systematic review and meta-analysis. JAMA. 2021; 325: 2357-2369 Google Scholar , 3 Ray JC Kapoor M Stark RJ et al. Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects. J Neurol Neurosurg Psychiatry. 2021; 92: 1325-1334 Google Scholar Particularly noteworthy is the good tolerability of these new drugs. Tolerability is important in migraine prophylaxis; the main disadvantage of traditional migraine prophylactic drugs was the high prevalence of adverse reactions, which resulted in poor compliance. Oral medication for acute therapy or prophylaxis also has the disadvantage that it is not uncommon for patients to forget to take the tablets. This problem is avoided by subcutaneous or intravenous administration of monoclonal antibodies against CGRP or its receptor. Calcitonin gene-related peptide-targeting drugs for migraine: how pharmacology might inform treatment decisionsMigraine is the second most disabling disorder across all age groups worldwide. Since 2018, two classes of drugs that inhibit the actions of calcitonin gene-related peptide (CGRP), which is implicated in migraine pathophysiology, have become available: gepants (CGRP receptor antagonists) and monoclonal antibodies directed against CGRP or its receptor. Despite phase 3 clinical trials and some real world evidence, knowledge of the pharmacology and related clinical effects of these drugs is low, and trial data are not necessarily generalisable to all populations. Full-Text PDF