Wedi Bettina
Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover, Germany.
Expert Opin Investig Drugs. 2023 Jul-Dec;32(11):1043-1054. doi: 10.1080/13543784.2023.2277385. Epub 2023 Nov 24.
Chronic urticaria (CU), including chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), is a prevalent, enduring, mast-cell driven condition that presents challenges in its management. There is a clear need for additional approved treatment options beyond H1 receptor antagonists and the anti-IgE monoclonal antibody (mAb), omalizumab. One of the latest therapeutic strategies targets KIT, which is considered the primary master regulator for mast cell-related disorders.
This review provides a status update on KIT inhibiting drugs in early clinical development for CU.
Whereas multi-targeted tyrosine kinase KIT inhibitors carry the risk of off-target toxicities, initial data from anti-KIT mAbs indicate significant potential in CSU and CIndU. The prolonged depletion of mast cells over several weeks by barzolvolimab could effectively control urticarial symptoms. Regarding safety, based on theoretical considerations and the available preliminary results, it is already evident that there may be more side effects compared to omalizumab. However, long-term safety data beyond 12 weeks are still lacking. The outcome of ongoing or planned clinical trials with several anti-KIT mAbs will need to demonstrate benefits compared to anti-IgE in CU or whether one approach is better suited for specific urticaria endotypes.
慢性荨麻疹（CU），包括慢性自发性荨麻疹（CSU）和慢性诱导性荨麻疹（CIndU），是一种常见的、持续性的、由肥大细胞驱动的疾病，其治疗面临挑战。除了H1受体拮抗剂和抗IgE单克隆抗体（mAb）奥马珠单抗外，显然还需要更多获批的治疗选择。最新的治疗策略之一是针对KIT，它被认为是肥大细胞相关疾病的主要主调节因子。
本综述提供了CU早期临床开发中KIT抑制药物的最新进展。
尽管多靶点酪氨酸激酶KIT抑制剂存在脱靶毒性风险，但抗KIT单克隆抗体的初步数据表明其在CSU和CIndU中具有显著潜力。巴佐伏单抗使肥大细胞持续数周耗竭可有效控制荨麻疹症状。关于安全性，基于理论考虑和现有初步结果，与奥马珠单抗相比，可能已经明显存在更多副作用。然而，仍缺乏超过12周的长期安全性数据。正在进行或计划进行的几种抗KIT单克隆抗体的临床试验结果，需要证明与抗IgE相比在CU中的益处，或者一种方法是否更适合特定的荨麻疹亚型。
