Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clincal Trial and Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Hematology, Wuhan No. 1 Hospital, Wuhan, China.
J Allergy Clin Immunol. 2020 Jul;146(1):137-146.e3. doi: 10.1016/j.jaci.2020.05.019. Epub 2020 May 26.
Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation.
This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019.
We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019.
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 After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study.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.
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.
越来越多的证据表明，Janus 相关激酶（JAK）抑制剂是一种有治疗潜力的靶点，值得进行快速研究。
本研究评估了 JAK1/2 抑制剂芦可替尼治疗 2019 年冠状病毒病（COVID-19）的疗效和安全性。
我们进行了一项前瞻性、多中心、单盲、随机对照的 II 期临床试验，纳入了严重 COVID-19 患者。
43 名患者被随机（1:1）分为芦可替尼联合标准治疗组（22 名患者）或安慰剂联合标准治疗组（21 名患者）。在排除了 2 名（1 名不符合条件，1 名退出）来自芦可替尼组的患者后，干预组的 20 名患者和对照组的 21 名患者被纳入研究。与标准治疗相比，芦可替尼联合标准治疗并未显著加速 COVID-19 重症患者的临床改善，尽管芦可替尼组患者的临床改善速度更快。在第 14 天，20 名芦可替尼组患者中有 18 名（90%）的 CT 检查改善，而对照组的 13 名（61.9%）患者中有 13 名（61.9%）患者的 CT 检查改善（P=0.0495）。对照组中有 3 名患者死于呼吸衰竭，28 天总死亡率为 14.3%；芦可替尼组无患者死亡。芦可替尼耐受性良好，毒性低，无新的安全信号。与对照组相比，芦可替尼组的 7 种细胞因子水平显著降低。
尽管未观察到统计学差异，但芦可替尼组患者的临床改善速度更快。芦可替尼组患者的胸部 CT 明显改善，淋巴细胞减少恢复更快，副作用谱良好，这为未来更大规模的临床试验提供了令人鼓舞和有价值的信息，以测试芦可替尼的疗效。
