Calcitonin gene-related peptide (CGRP), a 37 amino-acid neuropeptide found mostly in peptidergic sensory C-fibers, has been suggested to be implicated in the pathogenesis of migraine, which is one of the most common neurological disorders seen in medical practice, affecting almost 16% of the US population. While previously thought to be a vascular condition, migraine attacks are the result of neurogenic inflammation and peripheral/central sensitization through dysfunctional activation of the trigeminovascular system. To date, two classes of therapeutic agents have been developed to interrupt the function of CGRP: CGRP-targeted monoclonal antibodies (mAbs) and small-molecule antagonists (gepants). There are currently four CGRP-targeted mAbs and three gepants that are US Food and Drug Administration (FDA) approved for the treatment of migraine. Multiple phase II and III studies have established the efficacies and tolerability of these treatments. Previously, we reviewed the fundamental role of CGRP in migraine pathogenesis. Here, we discuss in depth the clinical evidence (randomized controlled trials and real-world studies), safety, and tolerability of CGRP-targeted mAbs and gepants for treating migraine.

降钙素基因相关肽 (CGRP) 是一种 37 个氨基酸的神经肽，主要存在于肽能感觉 C 纤维中，已被认为与偏头痛的发病机制有关，偏头痛是医学实践中最常见的神经系统疾病之一，影响了近 16% 的美国人口。虽然以前被认为是一种血管疾病，但偏头痛发作是神经源性炎症和通过三叉神经血管系统功能失调激活外周/中枢致敏的结果。迄今为止，已经开发了两类治疗剂来中断 CGRP 的功能：CGRP 靶向单克隆抗体 (mAb) 和小分子拮抗剂 (gepants)。目前有四种 CGRP 靶向 mAb 和三种 gepants 被美国食品和药物管理局 (FDA) 批准用于治疗偏头痛。多项 II 期和 III 期研究已经确定了这些治疗的有效性和耐受性。此前，我们回顾了 CGRP 在偏头痛发病机制中的基本作用。在这里，我们深入讨论了 CGRP 靶向 mAb 和 gepant 治疗偏头痛的临床证据（随机对照试验和真实世界研究）、安全性和耐受性。