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

https://doi.org/10.1016/j.jaci.2020.05.019Get rights and content

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 After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study.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.

Key words

Ruxolitinib
COVID-19
cytokine storm
efficacy
safety
randomized controlled trial

Abbreviations used

COVID-19
Coronavirus disease 2019
CT
Computed tomography
D
Day
ICU
Intensive care unit
IQR
Interquartile range
JAK
Janus-associated kinase
MIP-1α
Macrophage inflammatory protein 1α
MIP-1β
Macrophage inflammatory protein 1β
SARS
Severe acute respiratory syndrome
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SoC
Standard-of-care
VEGF
Vascular endothelial growth factor

Cited by (0)

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.

These authors contributed equally to this work.

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