Louisiana State University, Baton Rouge, Louisiana, USA.
Drugs Today (Barc). 2020 Nov;56(11):705-714. doi: 10.1358/dot.2020.56.11.3178111.
Sickle cell disease (SCD) is a genetic disorder characterized by a single gene mutation leading to polymerization of erythrocytes, with subsequent assumption of a "sickle" shape. However, polymerization is just one aspect of the disorder's pathology. It is also characterized by abnormalities in nitric oxide utilization and vasculopathy; generation of reactive oxygen species; hemolysis; hypercoagulability; and altered rheology including abnormal leukocyte rolling along endothelium, and sickle cell-endothelial and cell-cell adhesion. The latter phenomenon is associated with increased P- and E-selectin expression and creation of a proadhesive endothelial environment. The anti-P-selectin humanized monoclonal antibody crizanlizumab functions through selective inhibition of P-selectin. At a dose of 5 mg/kg in a clinical trial, it led to a 45.3% decline in the median annual crisis rate in individuals with SCD. Tolerability was good and the adverse event profile was acceptable. In this review, results of the clinical trials involving this drug and specific side effects are outlined. Analysis of cost efficacy is touched on, with an examination of the economic and social burden of SCD.
镰状细胞病（SCD）是一种遗传性疾病，其特征是单一基因突变导致红细胞聚合，随后呈现“镰状”。然而，聚合只是该疾病病理学的一个方面。它还表现为一氧化氮利用和血管病变异常；活性氧的产生；溶血；高凝状态；以及改变的流变性，包括白细胞异常在内皮滚动，镰状细胞内皮和细胞-细胞黏附。后一种现象与 P-和 E-选择素表达增加以及产生促黏附的内皮环境有关。抗 P-选择素人源化单克隆抗体 crizanlizumab 通过选择性抑制 P-选择素起作用。在临床试验中，剂量为 5mg/kg 时，导致 SCD 患者的中位年危机率下降 45.3%。耐受性良好，不良事件谱可接受。在这篇综述中，概述了涉及该药物的临床试验结果和特定的副作用。分析了成本效益，考察了 SCD 的经济和社会负担。
