Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial - 22/07/20

Doi : 10.1016/j.jaci.2020.05.019

Yang Cao, MD, PhD ^a,^b,^{^{∗
These authors contributed equally to this work.}}, Jia Wei, MD, PhD ^a,^b,^{^{∗
These authors contributed equally to this work.}}, Liang Zou, MD ^c,^{^{∗
These authors contributed equally to this work.}}, Tiebin Jiang, MD ^d,^{^{∗
These authors contributed equally to this work.}}, Gaoxiang Wang, MD, PhD ^a,^b, Liting Chen, PhD ^a,^b, Liang Huang, MD, PhD ^a,^b, Fankai Meng, MD, PhD ^a,^b, Lifang Huang, MD, PhD ^a,^b, Na Wang, MD, PhD ^a,^b, Xiaoxi Zhou, MD, PhD ^a,^b, Hui Luo, MD, PhD ^a,^b, Zekai Mao, MD, PhD ^a,^b, Xing Chen, MD, PhD ^a,^b, Jungang Xie, MD, PhD ^e, Jing Liu, MD, PhD ^d, Hui Cheng, MD ^c, Jianping Zhao, MD, PhD ^e, Gang Huang, PhD ^f,^⁎ , Wei Wang, MD, PhD ^g,^⁎ , Jianfeng Zhou, MD, PhD ^a,^b,^⁎
^a Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
^b Clincal Trial and Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
^c Department of Hematology, Wuhan No. 1 Hospital, Wuhan, China
^d Hematology Department of The Third Xiangya Hospital Central South University, Changsha, China
^e Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Site of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China
^f Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
^g Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

^∗Corresponding author: Jianfeng Zhou, MD, PhD, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei 430030, China.Department of HematologyTongji HospitalTongji Medical CollegeHuazhong University of Science and Technology1095 Jiefang AveWuhanHubei430030China^∗∗Gang Huang, PhD, Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Rm S7.224, Cincinnati, Ohio.Divisions of Pathology and Experimental Hematology and Cancer BiologyCincinnati Children’s Hospital Medical Center3333 Burnet AveRm S7.224CincinnatiOhio^∗∗∗Wei Wang, MD, PhD, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, Hubei, China.Department of NeurologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyNo. 1095 Jiefang AveWuhanHubei430030China

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Abstract

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.

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Key words : Ruxolitinib, COVID-19, cytokine storm, efficacy, safety, randomized controlled trial

Abbreviations used : COVID-19, CT, D, ICU, IQR, JAK, MIP-1α, MIP-1β, SARS, SARS-CoV-2, SoC, VEGF

Mappa

Methods

Study design

Participants

Randomization and masking

This work was supported by the Emergency Research Project of Tongji Hospital (to J.Z.), Emergency Research Project of Tongji Hospital of Huazhong University of Science and Technology (grant no. 2020kfyXGYJ045 to J.Z.), and Emergency Research Project of Hubei province (grant no. 2020FCA006 to W.W.). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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Vol 146 - N° 1

P. 137 - Luglio 2020 Ritorno al numero

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Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial - 22/07/20

Abstract

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Methods

Results

Conclusions

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