David Moreno-Ajona1,2, Abigail Pérez-Rodríguez1,2,3, Peter J Goadsby1,2. 1. Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London. 2. NIHR-Wellcome Trust King's Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, UK. 3. Department of Neurology, Hospital Nuestra Señora Del Rosario, Calle del Príncipe de Vergara, Madrid, Spain.
Abstract
PURPOSE OF REVIEW: Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug-drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients. RECENT FINDINGS: After some of the first-generation CGRP receptor antagonists, gepants, were not fully developed because of hepatotoxicity, the second generation of gepants have shown efficacy, safety and tolerability in recent clinical trials. SUMMARY: Both rimegepant and ubrogepant have published positive randomized placebo-controlled clinical trials data. Vazegepant is the first intranasal gepant for the acute treatment of migraine and has announced a positive phase II/III study. Daily rimegepant use has preliminary data to suggest efficacy. Atogepant has shown efficacy in migraine prevention in a phase II/III study. Most importantly, hepatotoxicity has not been reported in specifically designed phase I studies or long-term extension studies, with rimegepant or ubrogepant, or in a preventive study with atogepant. Given the preventive effect, it seems likely that gepants will not lead to medication overuse headache. They will likely have no cardiovascular warnings. Because of the particular benefit gepants may represent for these groups of patients, specific studies in patients with medication overuse headache, as well as those with comorbid cardiovascular diseases, would be of considerable interest.
PURPOSE OF REVIEW: Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug-drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients. RECENT FINDINGS: After some of the first-generation CGRP receptor antagonists, gepants, were not fully developed because of hepatotoxicity, the second generation of gepants have shown efficacy, safety and tolerability in recent clinical trials. SUMMARY: Both rimegepant and ubrogepant have published positive randomized placebo-controlled clinical trials data. Vazegepant is the first intranasal gepant for the acute treatment of migraine and has announced a positive phase II/III study. Daily rimegepant use has preliminary data to suggest efficacy. Atogepant has shown efficacy in migraine prevention in a phase II/III study. Most importantly, hepatotoxicity has not been reported in specifically designed phase I studies or long-term extension studies, with rimegepant or ubrogepant, or in a preventive study with atogepant. Given the preventive effect, it seems likely that gepants will not lead to medication overuse headache. They will likely have no cardiovascular warnings. Because of the particular benefit gepants may represent for these groups of patients, specific studies in patients with medication overuse headache, as well as those with comorbid cardiovascular diseases, would be of considerable interest.
Authors: Candler Paige; Isabel Plasencia-Fernandez; Moeno Kume; Melina Papalampropoulou-Tsiridou; Louis-Etienne Lorenzo; Eric T David; Lucy He; Galo L Mejia; Christopher Driskill; Francesco Ferrini; Andrew L Feldhaus; Leon F Garcia-Martinez; Armen N Akopian; Yves De Koninck; Gregory Dussor; Theodore J Price Journal: J Neurosci Date: 2022-01-20 Impact factor: 6.709
Authors: Irina I Belyaeva; Anna G Subbotina; Ivan I Eremenko; Vadim V Tarasov; Vladimir N Chubarev; Helgi B Schiöth; Jessica Mwinyi Journal: Front Pharmacol Date: 2022-02-10 Impact factor: 5.810