Sins Joep W R, Mager David J, Davis Shyrin C A T, Biemond Bart J, Fijnvandraat Karin
Department of Pediatric Hematology, Emma Children's Hospital, and.
Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
Blood Adv. 2017 Aug 22;1(19):1598-1616. doi: 10.1182/bloodadvances.2017007211.
Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs). Various treatments have been evaluated over the years. However, a clear overview is lacking. The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD. Primary outcomes were the number or duration of SCD-related pain days, VOCs, or hospital admissions for VOCs. Secondary outcomes included time to first VOC or hospital admission for a VOC. A standardized data extraction sheet was used. The methodological quality of studies was assessed using Cochrane's risk-of-bias tool. A total of 36 studies were included in this review, covering 26 different prophylactic interventions. The most promising interventions for reducing the frequency of either VOCs or hospitalizations were the oral antioxidants l-glutamine and ω-3 fatty acids and the IV antiadhesive agent crizanlizumab. Twenty-three studies did not show any beneficial effect of the intervention under investigation, and 6 studies were either too small or methodologically inadequate to draw conclusions. Because of the heterogeneity of interventions, no meta-analysis was performed. In conclusion, this review identified 3 promising pharmacotherapeutical strategies in the prevention of VOCs in SCD. Importantly, this study highlights the discrepancy between the significant burden of SCD worldwide and the low number of adequate trials performed. This review was registered at PROSPERO (CRD42015025250).
镰状细胞病（SCD）的特征是频繁发生疼痛性血管闭塞危象（VOCs）。多年来已对各种治疗方法进行了评估。然而，目前仍缺乏清晰的概述。本研究的目的是系统回顾除羟基脲之外预防VOCs的所有药物治疗策略。我们进行了系统的文献检索（MEDLINE、Embase、CENTRAL）。符合条件的研究为对照临床试验，评估针对降低SCD患者VOCs的药物治疗干预措施。主要结局是与SCD相关的疼痛天数、VOCs发作次数或因VOCs住院的次数或时长。次要结局包括首次发生VOC或因VOC住院的时间。使用标准化的数据提取表。采用Cochrane偏倚风险工具评估研究的方法学质量。本综述共纳入36项研究，涵盖26种不同的预防性干预措施。在降低VOCs发作频率或住院率方面，最有前景的干预措施是口服抗氧化剂L-谷氨酰胺和ω-3脂肪酸以及静脉注射抗黏附剂crizanlizumab。23项研究未显示所研究干预措施有任何有益效果，6项研究规模过小或方法学上存在不足，无法得出结论。由于干预措施的异质性，未进行荟萃分析。总之，本综述确定了3种在预防SCD患者VOCs方面有前景的药物治疗策略。重要的是，本研究凸显了全球范围内SCD的沉重负担与所开展的充分试验数量较少之间的差异。本综述已在国际前瞻性系统评价注册库（PROSPERO，注册号：CRD42015025250）登记。
