Developments in targeting calcitonin gene-related peptide

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.

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.

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.