Department of Neurology, University of California, San Francisco, USA.
Department of Neurology, University of California, Los Angeles, USA.
Drugs. 2018 Jun;78(9):913-928. doi: 10.1007/s40265-018-0923-5.
Migraine is a highly prevalent, complex neurological disorder. The burden of disease and the direct/indirect annual costs are enormous. Thus far, treatment options have been inadequate and mostly based on trial and error, leaving a significant unmet need for effective therapies. While the underlying pathophysiology of migraine is incompletely understood, blocking the calcitonin gene-related peptide (CGRP) using monoclonal antibodies targeting CGRP or its receptor and small molecule CGRP receptor antagonists (gepants) have emerged as a promising therapeutic opportunity for the management of migraine. In this review, we discuss new concepts in the pathophysiology of migraine and the role of CGRP, the current guidelines for treating migraine preventively, the medications that are being used, and their limitations. We then discuss small molecule CGRP receptor antagonists, monoclonal antibodies to CGRP ligand and receptor, as well as the detailed results of Phase II and III trials involving these novel treatments. We conclude with a discussion of the implications of blocking CGRP and its receptor.
偏头痛是一种高发、复杂的神经系统疾病。疾病负担和直接/间接年度成本巨大。迄今为止，治疗选择一直不足，主要基于反复试验，因此对于有效的治疗方法存在显著的未满足需求。尽管偏头痛的潜在病理生理学尚不完全清楚，但使用针对 CGRP 或其受体的单克隆抗体和小分子 CGRP 受体拮抗剂（ gepants ）阻断降钙素基因相关肽（CGRP）已成为管理偏头痛的一种有前途的治疗机会。在这篇综述中，我们讨论了偏头痛病理生理学的新概念以及 CGRP 的作用、预防性治疗偏头痛的现行指南、正在使用的药物及其局限性。然后，我们讨论了小分子 CGRP 受体拮抗剂、CGRP 配体和受体的单克隆抗体，以及涉及这些新型治疗方法的 II 期和 III 期试验的详细结果。最后，我们讨论了阻断 CGRP 和其受体的意义。
