Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial

Cao, Yang; Wei, Jia; Zou, Liang; Jiang, Tiebin; Wang, Gaoxiang; Chen, Liting; Huang, Liang; Meng, Fankai; Huang, Lifang; Wang, Na; Zhou, Xiaoxi; Luo, Hui; Mao, Zekai; Chen, Xing; Xie, Jungang; Liu, Jing; Cheng, Hui; Zhao, Jianping; Huang, Gang; Wang, Wei; Zhou, Jianfeng

Abstract Background Accumulating evidence proposed JAK inhibitors as therapeutic targets warranting rapid investigation. Objective This study evaluated the efficacy and safety of ruxolitinib, a Janus-associated kinase (JAK1/2) inhibitor, for COVID-19. Methods We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe COVID-19. Results Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus SoC treatment (22 patients) or placebo based on SoC treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in intervention group and 21 patients in control group were included in the study. Treatment with ruxolitinib plus SoC was not associated with significantly accelerated clinical improvement in severe patients with COVID-19, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed CT improvement at D14 compared with 13 (61.9%) patients from the control group (P = 0.0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at D28; 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 CT improvement, a faster recovery from lymphopenia and favorable side-effect profile in ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population. This trial is registered at www.chictr.org.cn as ChiCTR-OPN-2000029580.