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; Fang, Meng; Wang, Na; Zhou, Xiaoxi; Luo, Hui; Mao, Zekai; Chen, Xing; Xie, Jungang; Liu, Jing; Cheng, Hui; Zhao, Jianping; Huang, Gang; Wang, Wei; Zhou, Jianfeng

doi:10.1016/j.jaci.2020.05.019

Cited by 393 publications

(435 citation statements)

References 37 publications

Supporting

Mentioning

411

Contrasting

Unclassified

Order By: Relevance

“…We included a total of 33 clinical trials randomizing 13,312 participants ( Fig 1 ) [ 32 – 65 ]. We identified several trials, including participants suspected of COVID-19 [ 66 , 67 ]. None of the trials reported separate data on COVID-19 positive participants compared to the remaining participants.…”

Section: Resultsmentioning

confidence: 99%

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

et al. 2020

View full text Add to dashboard Cite

Background Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. Methods and findings This is the first edition of a living systematic review of randomized clinical trials comparing the effects of all treatment interventions for participants in all age groups with COVID-19. We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane guidelines, and our 8-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and nonserious adverse events. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until August 7, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 33 randomized clinical trials enrolling a total of 13,312 participants. All trials were at overall high risk of bias. We identified one trial randomizing 6,425 participants to dexamethasone versus standard care. This trial showed evidence of a beneficial effect of dexamethasone on all-cause mortality (rate ratio 0.83; 95% confidence interval [CI] 0.75–0.93; p < 0.001; low certainty) and on mechanical ventilation (risk ratio [RR] 0.77; 95% CI 0.62–0.95; p = 0.021; low certainty). It was possible to perform meta-analysis of 10 comparisons. Meta-analysis showed no evidence of a difference between remdesivir versus placebo on all-cause mortality (RR 0.74; 95% CI 0.40–1.37; p = 0.34, I 2 = 58%; 2 trials; very low certainty) or nonserious adverse events (RR 0.94; 95% CI 0.80–1.11; p = 0.48, I 2 = 29%; 2 trials; low certainty). Meta-analysis showed evidence of a beneficial effect of remdesivir versus placebo on serious adverse events (RR 0.77; 95% CI 0.63–0.94; p = 0.009, I 2 = 0%; 2 trials; very low certainty) mainly driven by respiratory failure in one trial. Meta-analyses and trial sequential analyses showed that we could exclude the possibility that hydroxychloroquine versus standard care reduced the risk of all-cause mortality (RR 1.07; 95% CI 0.97–1.19; p = 0.17; I 2 = 0%; 7 trials; low certainty) and ...

show abstract

Section: Resultsmentioning

confidence: 99%

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Additionally, recent research has indicated that targeting IFN-! using JAK inhibitors such as ruxolitinib, baricitinib, and tofacitinib offers effective therapeutic effects in treating severe COVID-19 patients 31,36,37 . Clinical trials of Type II interferon inhibitors in COVID-19 are under way (NCT04337359, NCT04359290, and NCT04348695) 31 .…”

Section: Discussionmentioning

confidence: 99%

IFN-γand TNF-αdrive aCXCL10+CCL2+ macrophage phenotype expanded in severe COVID-19 and other diseases with tissue inflammation

Zhang

Mears

Shakib

et al. 2020

Preprint

View full text Add to dashboard Cite

Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. Our cross-disease analysis revealed that an FCN1+ inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10+ CCL2+ inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1, and IL1B. We found that the CXCL10+ CCL2+ macrophages are transcriptionally similar to blood-derived macrophages stimulated with TNF-α and IFN-γ ex vivo. Our findings suggest that IFN-γ, alongside TNF-α, might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases, which may be targeted by existing immunomodulatory therapies.

show abstract

“…Vor dem Hintergrund einer fehlenden Standardtherapie bei lebensbedrohlicher COVID-19-Erkrankung wurden weltweit Patienten mit individuell indizierter Immunmodulation durch selektiv Zytokin-gerichtete Substanzen (Tocilizumab, Anakinra) oder Kinaseinhibitoren des Zytokin-Signalweges JAK/STAT (Ruxolitinib, Baricitinib) zur Dämpfung der Inflammation behandelt [ 5 , 6 , 9 , 17 , 26 ].…”

Section: Hintergrund Und Fragestellungunclassified

“…Der von uns beschriebene Ansatz, über gezielte Inhibition des JAK/STAT-Signalweges mit Ruxolitinib den Zytokinsturm der COVID-19-Erkrankung molekular zu bremsen, zeigt einen weiteren vielversprechenden Ansatz der personalisierten Inflammationshemmung der COVID-19-Hyperferritinämie [ 5 , 17 ]. Dabei ist die prospektive Risikostratifizierung mittels des neu entwickelten Score-Systems (CIS) hervorzuheben (Tab.…”

Section: Diskussionunclassified

Interdisziplinäres COVID-Board bei SARS-CoV-2-getriggerter hyperferritinämischer Inflammation

Rosée

Bremer

Rosée

et al. 2020

Med Klin Intensivmed Notfmed

View full text Add to dashboard Cite

Zusammenfassung Hintergrund Patienten mit schwerer COVID-19-Erkrankung entwickeln eine hyperferritinämische Inflammation, ein sepsisähnliches Immundysregulationssyndrom. Methode Retrospektive Kohortenanalyse nach Therapiestratifizierung in einer standortübergreifenden telemedizinischen Fallkonferenz. Frühzeitige, standardisierte Identifizierung von Patienten mit einem Risiko für einen schweren Verlauf (COVID-Inflammation-Score; CIS) und Intubationsvermeidung mit Schwerpunkt auf nichtinvasive Ventilation (NIV) sind Kernelemente des Behandlungsalgorithmus. Patienten mit lebensbedrohlicher Inflammation wurde ein individueller Heilversuch mit dem Immunmodulator Ruxolitinib angeboten. Ergebnisse Zwischen 04.03.2020 und 26.06.2020 wurden 196 COVID-19-Patienten behandelt. Der Altersmedian (70 Jahre) und die Komorbidität waren im Interstudienvergleich hoch. Die Gesamtmortalität lag bei 17,3 %, wobei bei der Hälfte der verstorbenen Patienten eine A‑priori-Therapielimitierung festgelegt war. Das CIS-Monitoring der mit Ruxolitinib behandelten Hochrisikopatienten (n = 20) ergab nach 5, 7 und 15 Tagen eine Inflammationssuppression um 42 % (15–70), 54 % (15–77) und 60 % (15–80). In dieser Gruppe lag die Mortalität bei 20 % (4/20). Die Gesamtmortalität adjustiert auf Patienten mit intendierter Maximaltherapie lag bei 8,7 % (17/196). Schlussfolgerung Die COVID-19-Pneumonie mit hyperferritinämischer Inflammation ist verwandt mit der Makrophagen-Aktivierungssyndrom-ähnlichen Sepsis. Eine interdisziplinäre Fallkonferenz als Qualitätsinstrument der Intensivmedizin zur Erfassung seltener sepsisähnlicher Krankheitsbilder wird vorgestellt.

show abstract

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

Cited by 393 publications

References 37 publications

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

IFN-γand TNF-αdrive aCXCL10+CCL2+ macrophage phenotype expanded in severe COVID-19 and other diseases with tissue inflammation

Interdisziplinäres COVID-Board bei SARS-CoV-2-getriggerter hyperferritinämischer Inflammation

Contact Info

Product

Resources

About