tetano
Editor, Senior Moderator
Front Med (Lausanne)
. 2022 Jan 27;8:800492.
doi: 10.3389/fmed.2021.800492. eCollection 2021.
The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis
Xueyang Zhang[SUP] 1 [/SUP], Lianhan Shang[SUP] 2 3 4 [/SUP], Guohui Fan[SUP] 3 4 5 [/SUP], Xiaoying Gu[SUP] 3 4 5 [/SUP], Jiuyang Xu[SUP] 1 3 4 [/SUP], Yeming Wang[SUP] 3 4 [/SUP], Lixue Huang[SUP] 3 4 6 [/SUP], Bin Cao[SUP] 3 4 6 7 [/SUP]
Affiliations
Abstract
Background: Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19.
Methods: Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR).
Results: Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis (n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51-0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41-0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42-0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49-0.78) with no increase in the risk of adverse events.
Conclusion: Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence.
Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.
Keywords: COVID-19; Janus kinase inhibitors; SARS-CoV-2; baricitinib; meta-analysis; systematic review.
. 2022 Jan 27;8:800492.
doi: 10.3389/fmed.2021.800492. eCollection 2021.
The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis
Xueyang Zhang[SUP] 1 [/SUP], Lianhan Shang[SUP] 2 3 4 [/SUP], Guohui Fan[SUP] 3 4 5 [/SUP], Xiaoying Gu[SUP] 3 4 5 [/SUP], Jiuyang Xu[SUP] 1 3 4 [/SUP], Yeming Wang[SUP] 3 4 [/SUP], Lixue Huang[SUP] 3 4 6 [/SUP], Bin Cao[SUP] 3 4 6 7 [/SUP]
Affiliations
- PMID: 35155477
- PMCID: PMC8828941
- DOI: 10.3389/fmed.2021.800492
Abstract
Background: Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19.
Methods: Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR).
Results: Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis (n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51-0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41-0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42-0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49-0.78) with no increase in the risk of adverse events.
Conclusion: Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence.
Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.
Keywords: COVID-19; Janus kinase inhibitors; SARS-CoV-2; baricitinib; meta-analysis; systematic review.