Seguridad cardiovascular de los nuevos fármacos para el tratamiento agudo y preventivo de la migraña: gepantes y ditanes / Cardiovascular safety of new drugs for the acute and preventive treatment of migraine: gepants and ditans

Introducción: La migraña es una patología neurológica prevalente caracterizada por ataques de cefalea incapacitantes. En las últimas décadas se han desarrollado nuevos fármacos específicos para el tratamiento agudo y preventivo de la migraña basados en su fisiopatología. Entre éstos se encuentran los antagonistas del péptido relacionado con el gen de la calcitonina (CGRP) (gepantes) y los agonistas selectivos del receptor serotoninérgico 5-HT1F (ditanes). El CGRP es un neuropéptido liberado por los terminales trigeminales que actúa como vasodilatador, provoca inflamación neurógena y, con ello, generación del dolor y sensibilización en la migraña. Posee, además, una potente acción vasodilatadora y participa en la regulación cardiovascular, razón por la cual se están llevando a cabo numerosos estudios que evalúan la seguridad vascular de actuar contra el CGRP. La alta selectividad de los ditanes para el receptor serotoninérgico 5-HT1F con una baja afinidad para otros receptores serotoninérgicos parece traducirse en un bajo o nulo efecto vasoconstrictor, que es mediado por la activación de los receptores 5-HT1B. Desarrollo: Nuestro objetivo es revisar la seguridad cardiovascular demostrada por estos nuevos fármacos para el tratamiento de la migraña analizando la evidencia publicada. Realizamos una búsqueda bibliográfica en la base de datos PubMed y una revisión de los ensayos clínicos publicados en clinicaltrial.gov. Incluimos revisiones bibliográficas, metaanálisis y ensayos clínicos en español e inglés. Analizamos los efectos adversos cardiovasculares informados. Conclusiones: Basándonos en los resultados hasta ahora publicados, podemos concluir que el perfil de seguridad cardiovascular de estos nuevos tratamientos es favorable. Para confirmar estos resultados son necesarios estudios de seguridad a más largo plazo.(AU)

Introduction: Migraine is a prevalent neurological condition characterised by disabling headache attacks. In recent decades, new drugs have been developed specifically for the acute and preventive treatment of migraine based on its pathophysiology. These include calcitonin gene-related peptide (CGRP) antagonists (CGRP) (gepants) and selective serotoninergic 5-HT1F receptor agonists (ditans). CGRP is a neuropeptide released by trigeminal terminals that acts as a vasodilator, causes neurogenic inflammation and thus generates pain and sensitisation in migraine. It also has a powerful vasodilatory action and is involved in cardiovascular regulation, which is why numerous studies are under way to assess the vascular safety of acting against CGRP. The high selectivity of ditans for the serotoninergic 5-HT1F receptor with a low affinity for other serotoninergic receptors seems to translate into little or no vasoconstrictor effect, which is mediated by the activation of 5-HT1B receptors. Development: The aim of our study is to review the cardiovascular safety demonstrated by these new drugs for the treatment of migraine by analysing the evidence published to date. We conducted a literature search in the PubMed database and a review of clinical trials published at clinicaltrial.gov. We included literature reviews, meta-analyses and clinical trials in English and Spanish. We analysed reported cardiovascular adverse effects. Conclusions: Based on the results published to date, we can conclude that the cardiovascular safety profile of these new treatments is favourable. Longer-term safety studies are needed to confirm these results.(AU)

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

CGRP en migraña: de la fisiopatología a la terapéutica / Calcitonin gene–related peptide in migraine: from pathophysiology to treatment

Introducción: En los últimos años se ha observado que moléculas como el péptido relacionado con el gen de la calcitonina (CGRP) y, en menor grado, el péptido activador de la adenilato-ciclasa pituitaria estaban elevadas durante los ataques de migraña y en la migraña crónica tanto en líquido cefalorraquídeo como en suero y que su reducción farmacológica tenía una significación clínica con una mejoría en la migraña de los pacientes. Es lógico por tanto que una de las principales líneas de investigación en migraña se base en el papel del CGRP en la fisiopatología de esta entidad. Desarrollo: Desde el Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología nos planteamos la redacción de este documento, cuyo objetivo es abordar, basándonos en la evidencia publicada, cuestiones tan importantes como el papel del CGRP en la fisiopatología de la migraña, el mecanismo de acción de los anticuerpos monoclonales y de los gepantes, el análisis crítico de los resultados de los diferentes estudios, el perfil del paciente que podría ser candidato al tratamiento con anticuerpos monoclonales y su impacto en términos de farmacoeconomía. Conclusiones: El desarrollo clínico de los gepantes, antagonistas del CGRP, para el tratamiento agudo del ataque de migraña y de los anticuerpos monoclonales contra ligando y contra el receptor del CGRP ofrecen resultados esperanzadores para nuestros pacientes. (AU)

Introduction: It has been observed in recent years that levels of such molecules as calcitonin gene–related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase–activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients’ migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. Development: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. Conclusions: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients. (AU)

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment. / CGRP en migraña: de la fisiopatología a la terapéutica.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.