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The Arrival of Anti-CGRP Monoclonal Antibodies in Migraine

Journal

NEUROTHERAPEUTICS
Volume 19, Issue 3, Pages 922-930

Publisher

SPRINGER
DOI: 10.1007/s13311-022-01230-x

Keywords

Monoclonal antibody; CGRP; Calcitonin gene-related peptide; Migraine; Neurogenic inflammation; Trigeminovascular system

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Remarkable advancements have been made in the field of migraine research and treatment, particularly with the discovery of CGRP functional blocking monoclonal antibodies (mAbs) as an effective preventive therapy for both chronic and episodic migraine. These mAbs offer advantages such as high affinity and selectivity, long-circulating plasma half-lives, and limited risk for side effects and drug-drug interactions. However, long-term safety and use during pregnancy should be further studied.
Remarkable advancements have been made in the field of migraine pathophysiology and pharmacotherapy over the past decade. Understanding the molecular mechanism of calcitonin gene-related peptide (CGRP) has led to the discovery of a novel class of drugs, CGRP functional blocking monoclonal antibodies (mAbs), for migraine prevention. CGRP is a neuropeptide inherently involved in migraine physiology where its receptors are found dispersed throughout the central and peripheral nervous systems. CGRP-targeted mAbs are effective in the preventive treatment of both chronic and episodic migraine. The advantages of mAbs over oral migraine preventives are numerous. Favorable attributes of the mAbs include high affinity and selectivity for CGRP molecular targets, long-circulating plasma half-lives, and limited risk for nonspecific hepatic and renal toxicity. This pharmacological profile leads to fewer off-target (side) effects and drug-drug interactions rendering mAbs an attractive alternative to traditional small molecule therapies, especially for the preventive treatment of migraine. MAbs display minimal drug interaction thus are excellent for patients prescribed with multiple medications. However, the long-term safety of CGRP blockade is incompletely known, and CGRP mAbs use should be avoided during pregnancy. CGRP mAbs represent a radical shift in preventing chronic and episodic migraine.

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