Silberstein Stephen, Lenz Robert, Xu Cen
Thomas Jefferson University, Philadelphia, PA, USA.
Amgen Inc., Thousand Oaks, CA, USA.
Headache. 2015 Sep;55(8):1171-82. doi: 10.1111/head.12642. Epub 2015 Aug 28.
Monoclonal antibodies (mAbs) are now an important part of the treatment armamentarium for a wide range of conditions including cancer, autoimmune diseases, inflammatory diseases of the joint and bowel, transplant rejection, and multiple sclerosis. Significant progress over the last 30 years in the development of therapeutic mAbs has resulted in improved efficacy and safety. Monoclonal antibodies approved for the treatment of neurological illnesses so far are limited to use in multiple sclerosis. Several therapeutic mAbs have completed phase 2 clinical trials for migraine prevention, and there are phase 3 trials underway for migraine prophylaxis and for cluster headache at the time of this writing.
The purpose of this review is to discuss the characteristics of mAbs, including their mechanism of action and safety profile, and briefly describe the mAbs being evaluated for the prevention of migraine and cluster headaches.
Monoclonal antibodies have several features that distinguish them from small molecules, including very high selectivity, relatively long half-life that generally allows for once or twice monthly dosing, and significantly reduced potential for drug-drug interactions or other nontarget related toxicities. The clinical development of mAbs that target calcitonin gene-related peptide and its receptor is underway and will evaluate this promising new drug class for the prevention of migraine and cluster headache.
单克隆抗体(mAbs)如今是治疗多种疾病的重要武器,这些疾病包括癌症、自身免疫性疾病、关节和肠道炎症性疾病、移植排斥反应以及多发性硬化症。过去30年里治疗性单克隆抗体的研发取得了重大进展,疗效和安全性都有所提高。目前获批用于治疗神经系统疾病的单克隆抗体仅限于用于多发性硬化症。几种治疗性单克隆抗体已完成预防偏头痛的2期临床试验,在撰写本文时,还有针对偏头痛预防和丛集性头痛的3期试验正在进行。
本综述的目的是讨论单克隆抗体的特性,包括其作用机制和安全性概况,并简要描述正在评估用于预防偏头痛和丛集性头痛的单克隆抗体。
单克隆抗体具有一些使其有别于小分子的特征,包括极高的选择性、相对较长的半衰期(通常允许每月给药一次或两次)以及显著降低的药物相互作用或其他非靶向相关毒性的可能性。针对降钙素基因相关肽及其受体的单克隆抗体的临床开发正在进行中,将评估这一有前景的新药类别用于预防偏头痛和丛集性头痛的效果。