Janus kinase inhibitors and major COVID-19 outcomes: time to forget the two faces of Janus! A meta-analysis of randomized controlled trials
- PMID: 34431004
- PMCID: PMC8384394
- DOI: 10.1007/s10067-021-05884-4
Janus kinase inhibitors and major COVID-19 outcomes: time to forget the two faces of Janus! A meta-analysis of randomized controlled trials
Abstract
Coronavirus disease-2019 (COVID-19) represents a global public health nightmare. The "cytokine storm," the most prominent underlying pathophysiologic mechanism of this disease, can theoretically be targeted at several stages. Janus kinase (JAK) inhibitors constitute a drug class that could ameliorate the inflammatory response and enhance antibody production. Herein, we aimed to evaluate the efficacy of JAK inhibitors in patients with COVID-19, performing the most updated relevant meta-analysis. We searched two major databases for randomized controlled trials (RCTs) enrolling adult patients with documented COVID-19 in the in-hospital setting, assigned either to JAK inhibitor treatment plus standard of care or standard of care alone. We set as primary efficacy outcome the endpoint of COVID-19 death on day 28 and as secondary efficacy composite outcome that of mechanical ventilation or initiation of extracorporeal membrane oxygenation (ECMO). We finally pooled data of interest from 4 RCTs in a total of 1338 subjects with documented COVID-19 infection, utilizing the following JAK inhibitors: baricitinib, ruxolitinib, tofacitinib, and nezulcitinib. Treatment with JAK inhibitor compared to control resulted in a significant reduction in the risk for COVID-19 death by 43%, while it also led to a significant decrease in the risk for mechanical ventilation or ECMO initiation by 36%. Herein, we demonstrate a clear benefit with JAK inhibitors added to standard of care in patients with COVID-19 in terms of risk reduction concerning major outcomes. Larger RCTs will elucidate their place in treatment armamentarium against COVID-19.
Keywords: COVID-19; Janus kinase inhibitor; Mechanical ventilation; Mortality.
© 2021. International League of Associations for Rheumatology (ILAR).
Figures
Similar articles
-
Clinical efficacy and safety of Janus kinase inhibitors for COVID-19: A systematic review and meta-analysis of randomized controlled trials.Int Immunopharmacol. 2021 Oct;99:108027. doi: 10.1016/j.intimp.2021.108027. Epub 2021 Jul 31. Int Immunopharmacol. 2021. PMID: 34343937 Free PMC article.
-
Janus Kinase inhibitors for the treatment of hospitalized patients with COVID-19.Curr Opin Crit Care. 2021 Oct 1;27(5):493-496. doi: 10.1097/MCC.0000000000000869. Curr Opin Crit Care. 2021. PMID: 34353999 Free PMC article. Review.
-
The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis.Front Med (Lausanne). 2022 Jan 27;8:800492. doi: 10.3389/fmed.2021.800492. eCollection 2021. Front Med (Lausanne). 2022. PMID: 35155477 Free PMC article.
-
Janus kinase inhibitors for hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials.Expert Rev Anti Infect Ther. 2022 May;20(5):773-779. doi: 10.1080/14787210.2022.2004120. Epub 2021 Nov 18. Expert Rev Anti Infect Ther. 2022. PMID: 34743661 Free PMC article.
-
Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis.Lancet. 2022 Jul 30;400(10349):359-368. doi: 10.1016/S0140-6736(22)01109-6. Lancet. 2022. PMID: 35908569 Free PMC article. Clinical Trial.
Cited by
-
Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells.Biomed Pharmacother. 2022 Mar;147:112614. doi: 10.1016/j.biopha.2022.112614. Epub 2022 Jan 4. Biomed Pharmacother. 2022. PMID: 34995938 Free PMC article.
-
Oral Janus kinase inhibitors for treating hospitalized patients with COVID-19: An updated systematic review and meta-analysis of randomized controlled trials.J Microbiol Immunol Infect. 2022 Dec;55(6 Pt 1):1025-1035. doi: 10.1016/j.jmii.2022.08.005. Epub 2022 Aug 17. J Microbiol Immunol Infect. 2022. PMID: 36031531 Free PMC article.
-
An Update on SARS-CoV-2 Clinical Trial Results-What We Can Learn for the Next Pandemic.Int J Mol Sci. 2023 Dec 26;25(1):354. doi: 10.3390/ijms25010354. Int J Mol Sci. 2023. PMID: 38203525 Free PMC article. Review.
-
Cytokine Storm in COVID-19: Insight into Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines.Medicines (Basel). 2024 Jul 18;11(7):14. doi: 10.3390/medicines11070014. Medicines (Basel). 2024. PMID: 39051370 Free PMC article. Review.
-
Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH).J Allergy Clin Immunol. 2022 May;149(5):1592-1606.e16. doi: 10.1016/j.jaci.2022.02.028. Epub 2022 Mar 15. J Allergy Clin Immunol. 2022. PMID: 35304157 Free PMC article.
References
-
- Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Kum E, Pardo-Hernandez H, Rochwerg B, Lamontagne F, Han MA, Liu Q, Agarwal A, Agoritsas T, Chu DK, Couban R, Darzi A, Devji T, Fang B, Fang C, Flottorp SA, Foroutan F, Ghadimi M, Heels-Ansdell D, Honarmand K, Hou L, Hou X, Ibrahim Q, Khamis A, Lam B, Loeb M, Marcucci M, McLeod SL, Motaghi S, Murthy S, Mustafa RA, Neary JD, Qasim A, Rada G, Riaz IB, Sadeghirad B, Sekercioglu N, Sheng L, Sreekanta A, Switzer C, Tendal B, Thabane L, Tomlinson G, Turner T, Vandvik PO, Vernooij RW, Viteri-García A, Wang Y, Yao L, Ye Z, Guyatt GH, Brignardello-Petersen R, Qasim A, Martinez JPD, Cusano E. Drug treatments for COVID-19: living systematic review and network meta-analysis. BMJ. 2020;371:m4852. - PMC - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical