Bristol Medical School, University of Bristol, Bristol, UK
Health Economics, PRECISIONheor, Los Angeles, California, USA.
BMJ Open. 2020 Sep 17;10(9):e034147. doi: 10.1136/bmjopen-2019-034147.
Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (≥16 years old) SCD patients.
The SLR included randomised controlled trials (RCTs) and uncontrolled studies. Bayesian NMA of VOC, all-cause hospitalisation days and adverse events were conducted.
The SLR identified 51 studies and 9 RCTs on 14 treatments that met the NMA inclusion criteria. The NMA found that crizanlizumab 5.0 mg/kg was associated with a reduction in VOC (HR 0.55, 95% credible interval (0.43, 0.69); Bayesian probability of superiority >0.99), all-cause hospitalisation days (0.58 (0.50, 0.68); >0.99) and no evidence of difference on adverse events (0.91 (0.59, 1.43) 0.66) or serious adverse events (0.93 (0.47, 1.87); 0.59) compared with placebo. The HR for reduction in VOC for crizanlizumab relative to L-glutamine was (0.67 (0.50, 0.88); >0.99). These results were sensitive to assumptions regarding whether patient age is an effect modifier.
This NMA provides preliminary evidence comparing the efficacy of crizanlizumab with other treatments for VOC prevention.
治疗镰状细胞病（SCD）患者血管阻塞性危象（VOC）的选择有限，尤其是在羟基脲治疗失败或禁忌的情况下。我们进行了系统文献回顾（SLR）和网络荟萃分析（NMA），以评估crizanlizumab 用于年龄较大的青少年和成年（≥16 岁）SCD 患者的疗效和安全性。
SLR 包括随机对照试验（RCT）和非对照研究。对 VOC、全因住院天数和不良事件进行贝叶斯 NMA。
SLR 确定了 51 项研究和 9 项符合 NMA 纳入标准的 RCT，NMA 发现 5.0mg/kg 的crizanlizumab 与降低 VOC（HR 0.55，95%可信区间（0.43，0.69）；优势概率 >0.99）、全因住院天数（0.58（0.50，0.68）；>0.99）和不良事件（0.91（0.59，1.43）0.66）或严重不良事件（0.93（0.47，1.87）；0.59）无差异与安慰剂相比。与 L-谷氨酰胺相比，crizanlizumab 降低 VOC 的 HR 为（0.67（0.50，0.88）；>0.99）。这些结果对患者年龄是否为效应修饰剂的假设敏感。
这项 NMA 提供了初步证据，比较了 crizanlizumab 与其他预防 VOC 治疗方法的疗效。
