Background

Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation.

Objective

This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019.

Methods

We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019.

Results

Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group.

Conclusions

Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.

中文翻译：

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鲁索替尼治疗 2019 年严重冠状病毒病 (COVID-19)：一项多中心、单盲、随机对照试验。

 背景

越来越多的证据表明 Janus 相关激酶 (JAK) 抑制剂是值得快速研究的治疗靶点。

 客观的

本研究评估了 JAK1/2 抑制剂鲁索替尼 (ruxolitinib) 对 2019 年冠状病毒病的疗效和安全性。

 方法

我们对 2019 年重症冠状病毒病患者进行了一项前瞻性、多中心、单盲、随机对照 II 期试验。

 结果

43 名患者被随机分配 (1:1) 接受鲁索替尼加标准护理治疗（22 名患者）或基于标准护理治疗的安慰剂（21 名患者）。从鲁索替尼组中排除 2 名患者（1 名不合格，1 名撤回同意）后，干预组 20 名患者和对照组 21 名患者纳入研究。鲁索替尼联合标准护理治疗与 2019 年冠状病毒病重症患者的临床改善速度显着加快无关，尽管鲁索替尼接受者的临床改善速度在数字上更快。鲁索替尼组的 18 名患者 (90%) 在第 14 天显示出计算机断层扫描改善，而对照组的患者有 13 名 (61.9%) ( P = .0495)。对照组有 3 名患者死于呼吸衰竭，第 28 天总死亡率为 14.3%；鲁索替尼组没有患者死亡。鲁索替尼耐受性良好，毒性低，没有新的安全信号。与对照组相比，鲁索替尼组的 7 种细胞因子水平显着降低。

 结论

尽管没有观察到统计学差异，但鲁索替尼接受者的临床改善在数值上更快。鲁索替尼组胸部计算机断层扫描的显着改善、淋巴细胞减少症的更快恢复以及良好的副作用特征都令人鼓舞，并为未来在更大人群中测试鲁索替尼疗效的试验提供了信息。