Whether the timing of patient randomization interferes with the assessment of the efficacy of ruxolitinib for severe COVID-19
Authors: Hailan Li, Huaping Liu
Journal: Journal of Allergy and Clinical Immunology (2020)

We read with great interest the article titled ''Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial'' by Cao et al.1Cao Y. Wei J. Zou L. Jiang T. Wang G. Chen L. et al.Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial.J Allergy Clin Immunol. 2020; 146: 137-146.e3Abstract Full Text Full Text PDF PubMed Scopus (340) Google Scholar The study, which finally included 41 patients, evaluated the efficacy and safety of ruxolitinib for severe COVID-19 cases. They found that ruxolitinib recipients had a significant chest computed tomography (CT) improvement, a faster recovery from lymphopenia, and favorable side-effect profile. However, we think it is appropriate to comment on the methods used in this study. First, the duration from illness onset to randomization, 22 days for the control group and 20 days for the ruxolitinib group, was not appropriate because according to literature reports,2Liu X. Zhou H. Zhou Y. Wu X. Zhao Y. Lu Y. et al.Risk factors associated with disease severity and length of hospital stay in COVID-19 patients.J Infect. 2020; 81: e95-e97Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 3Liang W.H. Guan W.J. Li C.C. Li Y.M. Liang H.R. Zhao Y. et al.Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China.Eur Respir J. 2020; 552000562Crossref PubMed Scopus (211) Google Scholar, 4Cao B. Wang Y. Wen D. Liu W. Wang J. Fan G. et al.A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19.N Engl J Med. 2020; 382: 1787-1799Crossref PubMed Scopus (3870) Google Scholar the course (from illness onset to discharge) of severe patients was about 27 to 30 days. Therefore, the patients may have passed the dangerous period at the 20th day and be in the end stage of the disease, which corresponds to the improvement period. Second, in terms of the extent of CT abnormalities, COVID-19 showed a marked increase from the subclinical period through the first and second weeks after illness onset, then decreased gradually in the third week.5Wang Y. Dong C. Hu Y. Li C. Ren Q. Zhang X. et al.Temporal changes of CT findings in 90 patients with COVID-19 pneumonia: a longitudinal study.Radiology. 2020; 296: E55-E64Crossref PubMed Scopus (651) Google Scholar, 6Zhou S. Zhu T. Wang Y. Xia L. Imaging features and evolution on CT in 100 COVID-19 pneumonia patients in Wuhan, China.Eur Radiol. 2020; 30: 5446-5454Crossref PubMed Scopus (81) Google Scholar, 7Shi H. Han X. Jiang N. Cao Y. Alwalid O. Gu J. et al.Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study.Lancet Infect Dis. 2020; 20: 425-434Abstract Full Text Full Text PDF PubMed Scopus (2593) Google Scholar Therefore, it is difficult to say whether the absorption of patients after the 20th day was the process of disease outcome or the effect of ruxolitinib. Finally, using the data of CT improvement at day 14 in Table III, we found that the P value between the control group and the treatment group was not .0495 but .079. Nevertheless, these small issues in no way detract from the outstanding work of Cao et al, which sheds light on the treatment of COVID-19. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trialJournal of Allergy and Clinical ImmunologyVol. 146Issue 1PreviewAccumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 146Issue 6PreviewWe appreciate Li and Liu1 for their interests in and comments on our article.2 Although most patients with severe coronavirus disease 2019 (COVID-19) have a self-limited disease course, about 10% to 15% subsequently developed critical illness and experienced a high mortality.3,4 In our randomized controlled trial, we evaluated whether the use of ruxolitinib was safe and superior in shortening the time to recovery and in preventing severe COVID-19 from progression. Given below are our point-to-point responses to each of the comments. Full-Text PDF