The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis

Wijaya, Indra; Andhika, Rizky; Huang, Ian; Purwiga, Aga; Budiman, Kevin Yonatan; Bashari, Muhammad Hasan; Reniarti, Lelani; Roesli, Rully M.A.

doi:10.1016/j.cegh.2021.100755

Cited by 36 publications

(35 citation statements)

References 38 publications

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“…Our patients were thoroughly monitored during their hospital stay, with lab tests every other day including biomarkers of infection, and an additional protocol for patients experiencing fever or clinical progression that included further diagnostic tests to exclude opportunistic infections and empirical antimicrobial therapy. While both agents have been linked with an increased risk of infections in patients with rheumatic disease ( 30 – 33 ), clinical trials, and meta-analyses with each drug have not verified a higher frequency of serious infections in patients with COVID-1 ( 9 , 10 , 34 – 36 ). We neither observed significant differences in the incidence of secondary infections with the combination of baricitinib plus tocilizumab compared to tocilizumab in our cohort even though all patients received additionally corticosteroids.…”

Section: Discussionmentioning

confidence: 99%

Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19

et al. 2021

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Background: Baricitinib is a Janus kinase (JAK) inhibitor with a broader anti-inflammatory activity than tocilizumab and an antiviral potential although no head-to-head trials are available. The benefits of adding baricitinib to patients with COVID-19 experiencing clinical progression despite the standard of care (SOC), including corticosteroids and tocilizumab, are also unknown.Methods: A cohort study included microbiologically confirmed COVID-19 hospitalizations. The primary outcome was 28-day mortality. Secondary outcomes were 60- and 90-day mortality, the composite outcome “28-day invasive mechanical ventilation (IMV) or death” and the safety of the combination. Propensity score (PS) matching was used to identify the association between baricitinib use and the outcomes of interest.Results: Of 1,709 admissions, 994 patients received corticosteroids and tocilizumab and 110 of them received baricitinib after tocilizumab. PS matched 190 (95:95) patients with baricitinib + SOC vs. SOC, of whom 69.5% received remdesivir. No significant effect of baricitinib was observed on 28-day [39 events; adjusted hazard ratio (aHR), 0.76; 95% CI, 0.31–1.86], 60-day (49 events, aHR, 1.17; 95% CI, 0.55–2.52), or 90-day mortality (49 events; aHR, 1.14; 95% CI, 0.53–2.47), or on the composite outcome 28-day IMV/death (aHR, 0.88; 95% CI, 0.45–1.72). Secondary infections during hospitalization were not different between groups (17.9 vs. 10.5%, respectively; p = 0.212) and thromboembolic events were higher with baricitinib (11.6% vs. 3.2%; p = 0.048), but differences vanished after the adjustment [aHR 1.89 (0.31–11.57), p = 0.490].Conclusion: The addition of baricitinib did not substantially reduce mortality in hospitalized patients with COVID-19 having clinical progression despite the therapy with tocilizumab and corticosteroids. The combination of baricitinib and tocilizumab was not associated with an increased risk of secondary infections or thromboembolic events.

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Section: Discussionmentioning

confidence: 99%

Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19

et al. 2021

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“…This meta-analysis has several strengths. First, only RCTs were included; thus, the evidence level of this study is potentially stronger than previous meta-analyses that included mainly observational studies [ 19 , 21 ]. Second, in contrast to previous meta-analyses [ 20 , 22 ] of RCTs that included 3 or 4 RCTs, our study included 5 RCTs with many more patients and could thus provide more information.…”

Section: Discussionmentioning

confidence: 99%

Janus kinase inhibitors for hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials

Lan

Wang

Chang³

et al. 2021

Expert Review of Anti-infective Therapy

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“…Janus kinase (JAK) inhibitors constitute such a treatment option, which has provided a significant improvement in surrogate COVID-19 outcomes in relevant observational studies, while some of the most recent meta-analyses of them have proven their efficacy [ 4 , 5 ]. A significant reduction in circulating levels of inflammatory cytokines, a rapid recovery of circulating T- and B-cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein have been proven with baricitinib use, a JAK inhibitor, in patients with severe COVID-19, as demonstrated in two observational studies from Italy [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Janus kinase inhibitors and major COVID-19 outcomes: time to forget the two faces of Janus! A meta-analysis of randomized controlled trials

et al. 2021

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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. Supplementary Information The online version contains supplementary material available at 10.1007/s10067-021-05884-4.

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The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis

Cited by 36 publications

References 38 publications

Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19

Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19

Janus kinase inhibitors for hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials

Janus kinase inhibitors and major COVID-19 outcomes: time to forget the two faces of Janus! A meta-analysis of randomized controlled trials

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