a Hematology Center , University of Campinas - UNICAMP , Campinas , Brazil.
Expert Opin Pharmacother. 2019 Feb;20(2):173-186. doi: 10.1080/14656566.2018.1548610. Epub 2018 Nov 30.
Sickle cell disease (SCD) is an inherited disease with lifelong morbidity, whose complications include frequent acute painful vaso-occlusive episodes (VOEs) that often require hospitalization. The only pharmacotherapy currently in regular use for SCD management is hydroxyurea (hydroxycarbamide).
We review recent advances in pharmacotherapy for SCD and summarize promising synthetic agents that are in late-stage development (phase 3) for SCD.
Emerging SCD therapies have been developed to target specific pathophysiological mechanisms of the disease, as either preventative or abortive approaches to VOEs. Continuous-use pharmacotherapeutics in late-phase development for VOE prevention include voxelotor (GBT440), which elevates hemoglobin oxygenation, and prasugrel, a platelet activation inhibitor. However, at least in the near future, it is probable that biological molecules will play a primary role in SCD preventative therapy; in combination with hydroxyurea, crizanlizumab, an anti-P-selectin monoclonal antibody, appears to reduce VOE frequency, while -glutamine was the first substance licensed by the FDA for use in SCD in 20 years. Synthetic drugs, however, may represent key approaches for the management of individuals upon hospitalization for VOE, a major challenge for SCD. For example, rivipansel (GMI-1070), a pan-selectin inhibitor, has shown encouraging effects on hospitalization time and opioid use.
镰状细胞病（SCD）是一种具有终身发病率的遗传性疾病，其并发症包括频繁的急性疼痛性血管阻塞性发作（VOEs），这些发作常需要住院治疗。目前，SCD 管理中常规使用的唯一药物疗法是羟基脲（hydroxycarbamide）。
我们回顾了 SCD 药物治疗的最新进展，并总结了处于后期开发阶段（第 3 阶段）的有前途的合成药物。
新兴的 SCD 治疗方法是针对该疾病的特定病理生理机制开发的，无论是作为 VOEs 的预防还是中止方法。处于后期开发阶段用于 VOE 预防的连续使用药物疗法包括 voxelotor（GBT440），它可提高血红蛋白的氧合作用，以及 prasugrel，一种血小板激活抑制剂。然而，至少在不久的将来，生物分子很可能在 SCD 预防性治疗中发挥主要作用；与羟基脲联合使用，抗 P-选择素单克隆抗体 crizanlizumab 似乎可降低 VOE 的频率，而 -谷氨酰胺是 20 年来 FDA 批准用于 SCD 的第一种物质。然而，合成药物可能代表 VOE 住院患者管理的关键方法，这是 SCD 的主要挑战。例如，pan-selectin 抑制剂 rivipansel（GMI-1070）在住院时间和阿片类药物使用方面显示出令人鼓舞的效果。
