Dataset Information

Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials.

ABSTRACT:

Background

To date, only dexamethasone and tocilizumab have been shown to reduce mortality in patients with COVID-19. Baricitinib is a Janus kinase 1/2 inhibitor with known anti-inflammatory and anti-viral properties. We performed a meta-analysis of RCTs assessing the role of baricitinib in hospitalised patients with COVID-19.

Methods

Electronic databases such as MEDLINE, EMBASE, and Cochrane Central were searched up until March 31, 2022, for RCTs evaluating the efficacy of baricitinib in hospitalised patients with COVID-19. The outcomes assessed were 28-day mortality, progression to invasive mechanical ventilation (IMV) or ECMO, progression to respiratory failure needing positive pressure ventilation, IMV or death, duration of hospitalisation and time to discharge. The meta-analysis was registered in the PROSPERO database (CRD42022314579).

Findings

Four studies (with 10,815 patients) were included in the analysis. Pooled analysis using random-effects model showed a statistically significant reduction in 28-day mortality (OR 0.69, 95% CI 0.50-0.94; p=0.04, I²=65%) and composite outcome of progression to severe disease needing positive pressure ventilation, IMV or death (OR 0.89, 95% CI 0.80-0.99, p= 0.03, I²=0%). There was a favorable trend towards reduced progression to IMV or ECMO (OR 0.76, 95% CI 0.58-1.01; p=0.06, I²=49%) in the baricitinib arm compared to standard therapy, even though it was not statistically significant. Statistical significance was achieved for all outcomes with fixed-effects model analysis.

Interpretation

In hospitalised patients with COVID-19, baricitinib was associated with reduced 28-day mortality although there was not a statistically significant reduction in progression to IMV or ECMO. Baricitinib used in conjunction with standard of care treatments is associated with improved mortality in hospitalised patients with COVID-19 disease.

Funding

None.

SUBMITTER: Selvaraj V

PROVIDER: S-EPMC9163705 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials.

Selvaraj Vijairam V Finn Arkadiy A Lal Amos A Khan Mohammad Saud MS Dapaah-Afriyie Kwame K Carino Gerardo P GP

EClinicalMedicine 20220603

<h4>Background</h4>To date, only dexamethasone and tocilizumab have been shown to reduce mortality in patients with COVID-19. Baricitinib is a Janus kinase 1/2 inhibitor with known anti-inflammatory and anti-viral properties. We performed a meta-analysis of RCTs assessing the role of baricitinib in hospitalised patients with COVID-19.<h4>Methods</h4>Electronic databases such as MEDLINE, EMBASE, and Cochrane Central were searched up until March 31, 2022, for RCTs evaluating the efficacy of barici ...[more]

PMID: 35677732

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Project description:BackgroundWe aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1-2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.MethodsThis randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.FindingsBetween Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45-0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72-0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.InterpretationIn patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Project description:ObjectiveTo assess the effects of telerehabilitation on clinical symptoms, physical function, psychological function and quality of life (QoL) in patients with post-COVID-19.DesignSystematic review and meta-analysis of randomised controlled trials (RCTs).Data sourcesPubMed, Web of Science, Embase and Cochrane Library were searched for publications from 1 January 2020 to 17 April 2024.Eligibility criteriaRCTs investigating the effects of telerehabilitation in patients with post-COVID-19 were included. The outcomes of interest encompassed clinical symptoms, physical function, psychological function and QoL. Only studies reported in English were included.Data extraction and synthesisTwo reviewers independently extracted data and evaluated the risk of bias. Statistical analysis was conducted using Review Manager V.5.3, employing mean difference (MD) with a 95% CI, and the corresponding P value was used to ascertain the treatment effect between groups. Heterogeneity was quantified using the I2 statistic. The quality of evidence was assessed by GRADE.Results16 RCTs (n=1129) were included in this systematic review, 15 of which (n=1095, 16 comparisons) were included in the meta-analysis. The primary pooled analysis demonstrated that, compared with no rehabilitation or usual care, telerehabilitation can improve physical function (measured by 30 s sit-to-stand test [6 RCTs, n=310, MD=1.58 stands, 95% CI 0.50 to 2.66; p=0.004]; 6 min walking distance [6 RCTs, n=324, MD=76.90 m, 95% CI 49.47 to 104.33; p<0.00001]; and physical function from the 36-item short-form health survey [5 RCTs, n=380, MD=6.12 units, 95% CI 2.85 to 9.38; p=0.0002]). However, the pooled results did not indicate significant improvements in clinical symptoms, pulmonary function, psychological function or QoL. The quality of the evidence was graded as low for physical function and Hospital Anxiety and Depression Scale-anxiety and very low for other assessed outcomes. The overall treatment completion rate was 78.26%, with no reports of severe adverse events in any included trials.ConclusionsDespite the lack of significant improvements in certain variables, telerehabilitation could be an effective and safe option for enhancing physical function in patients with post-COVID-19. It is advisable to conduct further well-designed trials to continue in-depth exploration of this topic.Study registrationPROSPERO, CRD42023404647.

Dataset Information

Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials.

Background

Methods

Findings

Interpretation

Funding

Publications

Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials.

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