Developments in targeting calcitonin gene-related peptide

ABSTRACT

Introduction

Calcitonin Gene-Related Peptide (CGRP)-targeted therapy has revolutionized migraine treatment since its first approval in 2018. CGRP-targeted therapy includes monoclonal antibodies (mAbs) and gepants, which modulate trigeminal nociceptive and inflammatory responses, alleviating pain sensitization involved in migraine pathogenesis. CGRP-targeted therapy is effective not only for migraine but also for other chronic headache disorders that share the CGRP pathway.

Areas Covered

The authors review the latest developments and evidence for CGRP-targeted therapy for episodic migraine and chronic migraine. In addition, the authors discuss the emerging evidence on response prediction, menstrual migraine, vestibular migraine, idiopathic intracranial hypertension, post-traumatic headache, and the relationship between selected migraine comorbidities and CGRP.

Expert opinion

Since the launch of CGRP-targeted therapy, many practical issues have been raised. Generally, it’s safe to combine CGRP-targeted mAbs and gepants; this is an excellent option for patients with partial response. When considering stopping CGRP-targeted therapy, although a disease-modifying effect is likely, the optimal time for discontinuation remains unknown. Finally, beyond migraine, CGRP-targeted therapy may be used for other chronic pain disorders and psychological comorbidities.

KEYWORDS:

• Calcitonin gene-related peptide
• migraine
• idiopathic intracranial hypertension
• vestibular migraine
• cluster headache
• post-traumatic headache

Article highlights

• Refractory migraine, which does not respond to traditional oral preventive treatments, may respond to CGRP mAb therapy.

• CGRP mAb therapy is likely beneficial for menstrual migraine, vestibular migraine, and idiopathic intracranial hypertension. Further studies are needed to explore its long-term benefits.

• Gepants are attractive alternatives to triptans due to the lack of vasoconstrictive effects and lower risk for medication overuse headache.

• Combining CGRP-targeting mAbs and gepants may be safe with additional benefits.

• CGRP-targeted therapy uses in post-traumatic headache should be further investigated given the shared pain pathway between migraine and post-traumatic pain.

Declaration of interest

Within the last 36 months, H Yuan has received funding from the National Institutes of Health (Grant No. R44NS115460) as well as institutional support for serving as an investigator from Teva Pharmaceuticals, AbbVie, and Trillen. They have also received consultancy fees from Salvia, AbbVie, Pfizer Inc, and Cerenovus; and royalties from Cambridge University Press and MedLink. S Silberstein has received or receives honoraria, as either a consultant and/or advisory panel member, from AbbVie, Amgen Inc, Aeon BioPharma, Axsome Therapeutics, Curelator, Inc, Epalex, GlaxoSmithKline Consumer Health Holdings, LLC.; electroCore Medical, LLC; Impel NeuroPharma, Inc.; Eli Lilly and Company; Medscape; Lundbeck; Nocera; Pulmatrix; Revance Therapeutics Inc; Salvia Bioelectronics; Satsuma Pharmaceuticals; Teva Pharmaceuticals; Theranica; Thermaquil and Trillen Medical Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer is an employee of Lundbeck AS. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.