Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Headache. 2018 May;58 Suppl 1:48-59. doi: 10.1111/head.13302.
Monoclonal antibodies targeting the calcitonin gene-related peptide pathway represent a new class of mechanism-specific, migraine-targeted therapies available for migraine prevention. To date, four monoclonal antibodies have demonstrated efficacy in phase II and III trials, significantly reducing migraine days per month versus placebo with rapid onset of action. While their efficacy may be considered similar to existing preventive options, their true value may lie in an improved tolerability profile, with high specificity and selectivity for the calcitonin gene-related peptide receptor or ligand reducing the potential for off-target binding and toxicity. The infrequent parenteral administration of these therapeutic proteins, and lack of requirement for dose titration, has potential to simplify treatment selection and use for clinicians and patients. However, the treatments have not yet been tested in real-world settings in patients with the range of comorbid conditions encountered in routine clinical practice, and longer-term data on safety, efficacy, and treatment persistence are required. If data from real-world settings can confirm the initial clinical trial findings, it is hoped that antibodies antagonizing the calcitonin gene-related peptide pathway will be able to improve quality of life for patients with episodic and chronic migraine, and help relieve the huge patient and societal burden of migraine. Novel treatments designed to target the specific pathophysiology of migraine could have an important place in future migraine management.
针对降钙素基因相关肽通路的单克隆抗体代表了一类新的机制特异性、偏头痛靶向治疗药物,可用于偏头痛预防。迄今为止,已有四种单克隆抗体在 II 期和 III 期临床试验中显示出疗效,与安慰剂相比,每月偏头痛天数显著减少,起效迅速。虽然它们的疗效可能被认为与现有预防选择相似,但它们的真正价值可能在于改善耐受性,对降钙素基因相关肽受体或配体具有高特异性和选择性,从而降低脱靶结合和毒性的可能性。这些治疗性蛋白的给药频率较低,不需要剂量滴定,这有可能简化临床医生和患者的治疗选择和使用。然而,这些治疗方法尚未在真实环境中对伴有常规临床实践中遇到的各种合并症的患者进行测试,还需要长期的安全性、疗效和治疗持久性数据。如果真实环境数据能够证实初始临床试验结果,那么希望拮抗降钙素基因相关肽通路的抗体能够提高发作性和慢性偏头痛患者的生活质量,并帮助缓解偏头痛给患者和社会带来的巨大负担。旨在针对偏头痛特定病理生理学的新型治疗方法可能在未来的偏头痛管理中占有重要地位。