Skip to content
2000
Volume 7, Issue 2
  • ISSN: 2666-7967
  • E-ISSN: 2666-7975

Abstract

Objectives

Global healthcare faces challenges in combating COVID-19, with rising cases despite widespread vaccination. Severe COVID-19 cases, marked by acute respiratory distress and cytokine release syndrome, highlight the importance of managing cytokine storms. Janus kinase (JAK) inhibitors, such as tofacitinib, show promise in this regard. While tofacitinib is recommended for severe cases, challenges include adverse effects, conflicting studies, and the need for further investigation of new virus strains. Overcoming these hurdles is crucial for developing an effective treatment protocol and reducing COVID-19 mortality.

Methods

This study conducted a comprehensive search across PubMed, Scopus, and ISI Web of Science for observational studies on tofacitinib treatment in human adults with COVID-19. The search covered a specified period up to 2024. Data extraction, including study characteristics and quality assessment, employed the Newcastle Ottawa Scale and a modified Cochrane tool. Statistical analysis, conducted with Comprehensive Meta-Analysis Software, assessed heterogeneity and significance levels.

Results and Discussion

The meta-analysis of the three studies showed a significant reduction in mortality (Risk Ratio: 0.372, 95% CI: 0.213–0.649, -value = 0.001) with low heterogeneity (Cochrane -value = 0.793), while no significant reduction in the need for mechanical ventilation was observed (Cochrane -value = 0.194).

Conclusion

Tofacitinib administration shows a significant reduction in COVID-19 mortality. However, the limited studies on its efficacy highlight the need for cautious interpretation in clinical assessments.

Loading

Article metrics loading...

/content/journals/covid/10.2174/0126667975308179241022110314
2024-10-29
2026-01-02
Loading full text...

Full text loading...

References

  1. LaiC.C. LiuY.H. WangC.Y. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths.J. Microbiol. Immunol. Infect.202053340441210.1016/j.jmii.2020.02.012 32173241
    [Google Scholar]
  2. MaslennikovR. IvashkinV. VasilievaE. Tofacitinib reduces mortality in coronavirus disease 2019 tofacitinib in COVID-19.Pulm. Pharmacol. Ther.20216910203910.1016/j.pupt.2021.102039 34023513
    [Google Scholar]
  3. KimJ.S. LeeJ.Y. YangJ.W. Immunopathogenesis and treatment of cytokine storm in COVID-19.Theranostics202111131632910.7150/thno.49713 33391477
    [Google Scholar]
  4. SiemieniukR.A.C. BartoszkoJ.J. ZeraatkarD. Drug treatments for COVID-19: Living systematic review and network meta-analysis.BMJ2020370m298010.1136/bmj.m2980 32732190
    [Google Scholar]
  5. NgamprasertchaiT. KajeekulR. SivakornC. Efficacy and safety of immunomodulators in patients with COVID-19: A systematic review and network meta-analysis of randomized controlled trials.Infect. Dis. Ther.202211123124810.1007/s40121‑021‑00545‑0 34757578
    [Google Scholar]
  6. NiuJ. LinZ. HeZ. Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis.Front. Med. (Lausanne)2022997368810.3389/fmed.2022.973688 36507538
    [Google Scholar]
  7. LuoW. LiY.X. JiangL.J. ChenQ. WangT. YeD.W. Targeting JAK-STAT signaling to control cytokine release syndrome in COVID-19.Trends Pharmacol. Sci.202041853154310.1016/j.tips.2020.06.007 32580895
    [Google Scholar]
  8. YeQ. WangB. MaoJ. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19.J. Infect.202080660761310.1016/j.jinf.2020.03.037 32283152
    [Google Scholar]
  9. DoshiP.B. WhittleJ.S. DunganG. The ventilatory effect of high velocity nasal insufflation compared to non-invasive positive-pressure ventilation in the treatment of hypercapneic respiratory failure: A subgroup analysis.Heart Lung202049561061510.1016/j.hrtlng.2020.03.008 32273085
    [Google Scholar]
  10. McLornanD.P. PopeJ.E. GotlibJ. HarrisonC.N. Current and future status of JAK inhibitors.Lancet20213981030280381610.1016/S0140‑6736(21)00438‑4 34454676
    [Google Scholar]
  11. MeletiadisJ. TsiodrasS. TsirigotisP. Interleukin-6 blocking vs. JAK-STAT inhibition for prevention of lung injury in patients with COVID-19.Infect. Dis. Ther.20209470771310.1007/s40121‑020‑00326‑1 32789663
    [Google Scholar]
  12. HuangJ. ZhouC. DengJ. ZhouJ. JAK inhibition as a new treatment strategy for patients with COVID-19.Biochem. Pharmacol.202220211516210.1016/j.bcp.2022.115162 35787993
    [Google Scholar]
  13. BhimrajA. MorganR.L. ShumakerA.H. Infectious Diseases Society of America Guidelines on the treatment and management of patients with coronavirus disease 2019 (COVID-19).Clin. Infect. Dis.2020ciaa47810.1093/cid/ciaa478 32338708
    [Google Scholar]
  14. Higgins JPt, Green SCochrane handbook for systematic reviews of interventions.In: 2011Available from: https://handbook-5-1.cochrane.org/
  15. HuttonB. SalantiG. CaldwellD.M. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations.Ann. Intern. Med.20151621177778410.7326/M14‑2385 26030634
    [Google Scholar]
  16. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis.2011Available from: https://www.evidencebasedpublichealth.de/download/Newcastle_Ottowa_Scale_Pope_Bruce.pdf
  17. HigginsJ.P. AltmanD.G. Assessing risk of bias in included studies.Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series. HigginsJ.P.T. GreenS. Wiley200810.1002/9780470712184.ch8
    [Google Scholar]
  18. HigginsJ.P.T. ThompsonS.G. Quantifying heterogeneity in a meta‐analysis.Stat. Med.200221111539155810.1002/sim.1186 12111919
    [Google Scholar]
  19. SinghP.K. LalwaniL.K. GovindagoudarM.B. Tofacitinib associated with reduced intubation rates in the management of severe COVID-19 pneumonia: A preliminary experience.Indian J. Crit. Care Med.2021251011081112 34916741
    [Google Scholar]
  20. HayekM.E. MansourM. NdetanH. Anti-inflammatory treatment of COVID-19 pneumonia with tofacitinib alone or in combination with dexamethasone is safe and possibly superior to dexamethasone as a single agent in a predominantly African American cohort.Mayo Clin. Proc. Innov. Qual. Outcomes20215360561310.1016/j.mayocpiqo.2021.03.007 33817559
    [Google Scholar]
  21. DowtyM.E. LinJ. RyderT.F. The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans.Drug Metab. Dispos.201442475977310.1124/dmd.113.054940 24464803
    [Google Scholar]
  22. ZanzaC. RomenskayaT. ManettiA. Cytokine storm in COVID-19: Immunopathogenesis and therapy.Medicina (Kaunas)202258214410.3390/medicina58020144 35208467
    [Google Scholar]
  23. KuboS YamaokaK KondoM The JAK inhibitor, tofacitinib, reduces the T cell stimulatory capacity of human monocyte-derived dendritic cells.Ann Rheum Dis73: 2192-8.2013;10.1136/annrheumdis‑2013‑203756
    [Google Scholar]
  24. SoyM. KeserG. AtagündüzP. TabakF. AtagündüzI. KayhanS. Cytokine storm in COVID-19: Pathogenesis and overview of anti-inflammatory agents used in treatment.Clin. Rheumatol.20203972085209410.1007/s10067‑020‑05190‑5 32474885
    [Google Scholar]
  25. TanakaY. LuoY. O’SheaJ.J. NakayamadaS. Janus kinase-targeting therapies in rheumatology: A mechanisms-based approach.Nat. Rev. Rheumatol.202218313314510.1038/s41584‑021‑00726‑8 34987201
    [Google Scholar]
  26. GuimarãesP.O. QuirkD. FurtadoR.H. Tofacitinib in patients hospitalized with COVID-19 pneumonia.N. Engl. J. Med.2021385540641510.1056/NEJMoa2101643 34133856
    [Google Scholar]
  27. DowtyM.E. LinT.H. JessonM.I. Janus kinase inhibitors for the treatment of rheumatoid arthritis demonstrate similar profiles of in vitro cytokine receptor inhibition.Pharmacol. Res. Perspect.201976e0053710.1002/prp2.537 31832202
    [Google Scholar]
  28. XuS. IlyasI. WengJ. Endothelial dysfunction in COVID-19: An overview of evidence, biomarkers, mechanisms and potential therapies.Acta Pharmacol. Sin.202344469570910.1038/s41401‑022‑00998‑0 36253560
    [Google Scholar]
  29. ZhangF. MearsJ.R. ShakibL. IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation.Genome Med.20211316410.1186/s13073‑021‑00881‑3 33879239
    [Google Scholar]
  30. PattisonM.J. MacKenzieK.F. ArthurJ.S.C. Inhibition of JAKs in macrophages increases lipopolysaccharide-induced cytokine production by blocking IL-10-mediated feedback.J. Immunol.201218962784279210.4049/jimmunol.1200310 22904308
    [Google Scholar]
  31. FredeN. LorenzettiR. HüppeJ.M. JAK inhibitors differentially modulate B cell activation, maturation and function: A comparative analysis of five JAK inhibitors in an in-vitro B cell differentiation model and in patients with rheumatoid arthritis.Front. Immunol.202314108798610.3389/fimmu.2023.1087986 36776828
    [Google Scholar]
/content/journals/covid/10.2174/0126667975308179241022110314
Loading
/content/journals/covid/10.2174/0126667975308179241022110314
Loading

Data & Media loading...

Supplements

PRISMA checklist as a supplementary material is available on the publisher's website along with the published article.


  • Article Type:
    Research Article
Keyword(s): COVID-19; cytokine; janus kinase inhibitors; SARS-CoV-2; tofacitinib; vaccination
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test