Monoclonal antibody therapies for migraine: principles and applications

Migraine is a highly prevalent, disabling neurological disorder imposing a substantial global socioeconomic burden. The calcitonin gene–related peptide (CGRP) pathway plays a pivotal role in trigeminovascular activation, neurogenic inflammation, and pain transmission, making it a primary target for disease-specific preventive strategies.This review provides a comprehensive synthesis of anti-CGRP monoclonal antibodies (mAbs)—erenumab, fremanezumab, galcanezumab, and eptinezumab—integrating biological and pharmacological principles, clinical efficacy across migraine subtypes, real-world evidence, and safety considerations in patients with complex comorbidities. PubMed, Scopus, and Web were searched for preclinical studies, randomized clinical trials, meta-analyses, and real-world registries examining anti-CGRP mAbs and CGRP receptor antagonists in migraine prevention and acute treatment.Anti-CGRP mAbs offer a precision mechanism, long half-lives, rapid onset of action, and high target specificity without systemic neuro-modulatory side effects. Clinical trials and real-world studies consistently demonstrate robust efficacy in reducing monthly migraine days, acute medication use, and disability in both episodic and chronic migraine, including difficult-to-treat and treatment-refractory populations. Furthermore, emerging evidence highlights their efficacy in medication-overuse headache (MOH) without requiring mandatory prior withdrawal. Their favorable pharmacokinetic profile—characterized by reticuloendothelial catabolism and minimal drug-drug interactions—makes them safe across various comorbid conditions, such as depression, cardiovascular risk factors, diabetes, and organ impairment, although specific monitoring for hypertension and vascular events is warranted.Anti-CGRP mAbs represent a transformative paradigm in migraine prevention. Their combination of biological specificity, sustained real-world effectiveness, and favorable safety profile establishes them as a foundation of modern precision management in migraine.