Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial.

The SUSTAIN study showed a reduction of vaso-occlusive crises in patients treated with 5 mg/kg crizanlizumab, compared with placebo.

SUSTAIN 研究显示，与安慰剂相比，接受 5 mg/kg Crizanlizumab 治疗的患者血管阻塞危机有所减少。

The STAND study aimed to evaluate the efficacy and safety of two doses (5·0 mg/kg and 7·5 mg/kg) of crizanlizumab in sickle cell disease.

STAND研究旨在评估两种剂量（5.0 mg/kg和7.5 mg/kg）的crizanlizumab在镰状细胞病中的疗效和安全性。

Herein, we report the primary analysis results of STAND.

在此，我们报告了STAND的主要分析结果。

Methods

STAND is a phase 3, multicentre, randomised, double-blindstudy of patients with sickle cell disease aged 12 years and older done at 65 sites in 21 countries.

STAND 是一项针对12岁及以上镰状细胞病患者的第3阶段、多中心、随机、双盲研究，在21个国家的65个地点进行。

Patients were randomly assigned (1:1:1) to receive either 5·0 mg/kg of crizanlizumab, 7·5 mg/kg of crizanlizumab, or placebo, in addition to standard of care, for 1 year.

患者被随机分配（1:1:1）接受5.0 mg/kg的crizanlizumab、7.5 mg/kg的crizanlizumab或安慰剂，加上标准治疗，为期1年。

The primary endpoint was the annualised rate of vaso-occlusive crises leading to a health-care visit over the first-year post-randomisation.

主要终点是随机化后第一年内因血管闭塞性危机导致的医疗访问的年化率。

The secondary objectives included assessing crizanlizumab's safety.

次要目标包括评估crizanlizumab的安全性。

The trial is registered at ClinicalTrials.gov (NCT03814746) and is ongoing.

该试验已在ClinicalTrials.gov注册（NCT03814746），目前正在进行中。

Results

Between July 26, 2019, and Aug 31, 2022, 252 patients were enrolled and treated.

在2019年7月26日至2022年8月31日期间，共有252名患者被纳入并接受了治疗。

The primary analysis showed an adjusted annualised rate of vaso-occlusive crises of 2·49 (95% CI 1·90-3·26) in the crizanlizumab 5·0 mg/kg group, 2·04 (1·56-2·65) in the 7·5 mg/kg group, and 2·30 (1·75-3·01) in the placebo group.

主要分析显示，在接受5.0 mg/kg剂量的crizanlizumab治疗组中，血管阻塞危机的调整年化发生率为2.49（95%置信区间1.90-3.26），在7.5 mg/kg剂量组为2.04（1.56-2.65），而在安慰剂组为2.30（1.75-3.01）。

Ratios of adjusted annualised rates of vaso-occlusive crises leading to health-care visits were 1·08 (95% CI 0·76-1·55, p>0·999) for 5·0 mg/kg and 0·89 (0·62-1·27, p>0·999) for 7·5 mg/kg vs placebo.

导致医疗访问的血管阻塞危机的调整年化发生率比为5.0 mg/kg剂量组为1.08（95%置信区间0.76-1.55，p>0.999），7.5 mg/kg剂量组为0.89（0.62-1.27，p>0.999）与安慰剂组相比。

The incidenceof adverse events was similar across treatment groups.

不同治疗组的不良事件发生率相似。

Grade 3 or higher adverse events were observed less frequently in the placebo and crizanlizumab 7·5 mg/kg groups (27 [32%] of 85 and 32 [39%] of 83, respectively) than in the 5·0 mg/kg group (47 [56%] of 84).

在安慰剂组和crizanlizumab 7.5 mg/kg组中，观察到3级或更高级别的不良事件较少（分别为85人中的27人[32%]和83人中的32人[39%]），而在5.0 mg/kg组中则较多（84人中的47人[56%]）。

Serious adverse events (all grades) were also less frequent in the placebo and crizanlizumab 7·5 mg/kg groups (26 [31%] and 22 [27%], respectively) than in the 5·0 mg/kg group (35 [42%]).

严重不良事件（所有级别）在安慰剂组和crizanlizumab 7.5 mg/kg组中也较少（分别为26例[31%]和22例[27%]），与5.0 mg/kg组相比（35例[42%]）。

interpretation

The STAND study supports the safety and tolerability of crizanlizumab in the treatment of sickle cell disease.

STAND研究支持crizanlizumab在治疗镰状细胞病中的安全性和耐受性。

The primary analysis showed no significant difference in efficacy between crizanlizumab and placebo.

主要分析显示，crizanlizumab与安慰剂在疗效上没有显著差异。

Factors including the COVID-19 pandemic, global enrolment with varied patterns of health-care use and vaso-occlusive crisis management as well as the commercial availability of crizanlizumab might have influenced these results.

包括COVID-19大流行、全球招募中不同模式的卫生保健使用和血管阻塞危机管理以及crizanlizumab的商业可用性等因素可能影响了这些结果。

The safety profile of crizanlizumab was consistent with that in previous reports, without new safety concerns.

克里赞利珠单抗的安全性特征与先前报告一致，未出现新的安全问题。

funding

Novartis Pharmaceuticals.

诺华制药公司。