Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

The Lancet, Journal Year: 2022, Volume and Issue: 400(10349), P. 359 - 368

Published: July 1, 2022

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

Language: Английский

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Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 19, 2023

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism transmembrane transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, other specific molecules activate JAK-STAT signaling drive a series physiological pathological processes, including proliferation, metabolism, immune response, inflammation, malignancy. Dysregulated related genetic mutations are strongly associated activation cancer progression. Insights into structures functions have led development approval diverse drugs for clinical treatment diseases. Currently, been developed mainly target commonly divided three subtypes: cytokine or receptor antibodies, JAK inhibitors, STAT inhibitors. And novel agents also continue be tested in preclinical studies. effectiveness safety each kind drug warrant further scientific trials before put being applications. Here, we review current understanding fundamental composition function pathway. We discuss advancements JAK-STAT–related pathogenic mechanisms; targeted therapies various diseases, especially disorders, cancers; newly inhibitors; challenges directions field.

Language: Английский

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The development of COVID-19 treatment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 26, 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic named disease 2019 (COVID-19) that has become the greatest worldwide public health threat this century. Recent studies have unraveled numerous mysteries SARS-CoV-2 pathogenesis and thus largely improved COVID-19 vaccines therapeutic strategies. However, important questions remain regarding its therapy. In review, recent research advances on mechanism are quickly summarized. We mainly discuss current therapy strategies for COVID-19, with an emphasis antiviral agents, neutralizing antibody therapies, Janus kinase inhibitors, steroids. When necessary, specific mechanisms history present, representative described in detail. Finally, we key outstanding future directions development treatment.

Language: Английский

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Therapeutic advances in COVID-19

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 19(1), P. 38 - 52

Published: Oct. 17, 2022

Language: Английский

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Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients With COVID-19 (September 2022)

Clinical Infectious Diseases, Journal Year: 2022, Volume and Issue: 78(7), P. e250 - e349

Published: Sept. 5, 2022

Abstract There are many pharmacologic therapies that being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended support patients, clinicians, other healthcare professionals in their decisions about management patients COVID-19. In March 2020, the Infectious Diseases Society America (IDSA) formed a multidisciplinary guideline panel infectious pharmacists, methodologists varied areas expertise regularly review make recommendations persons process approach followed rapid recommendation development checklist. prioritized questions outcomes. A systematic peer-reviewed grey literature conducted at regular intervals. Grading Recommendations Assessment, Development, Evaluation (GRADE) assess certainty recommendations. Based on most recent search 31 May 2022, IDSA has made 32 following groups/populations: pre- postexposure prophylaxis, ambulatory mild-to-moderate disease, hospitalized mild-to-moderate, severe but not critical, critical disease. As these guidelines, can be found online at: https://idsociety.org/COVID19guidelines. At inception its work, expressed overarching goal recruited into ongoing Since then, trials were provided much-needed COVID-19 therapies. still remain unanswered as pandemic evolved, which we hope future answer.

Language: Английский

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Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial

The Lancet Respiratory Medicine, Journal Year: 2022, Volume and Issue: 10(9), P. 888 - 899

Published: May 23, 2022

Language: Английский

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

EClinicalMedicine, Journal Year: 2022, Volume and Issue: 49, P. 101489 - 101489

Published: June 3, 2022

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 known anti-inflammatory anti-viral properties. We performed meta-analysis of RCTs assessing the role baricitinib hospitalised Electronic databases such as MEDLINE, EMBASE, Cochrane Central were searched up until March 31, 2022, for evaluating efficacy The outcomes assessed 28-day mortality, progression invasive mechanical ventilation (IMV) or ECMO, respiratory failure needing positive pressure ventilation, IMV death, duration hospitalisation time discharge. was registered PROSPERO database (CRD42022314579). Four studies (with 10,815 patients) included analysis. Pooled analysis using random-effects model showed statistically significant reduction (OR 0.69, 95% CI 0.50-0.94; p=0.04, I2=65%) composite outcome severe disease death 0.89, 0.80-0.99, p= 0.03, I2=0%). There favorable trend towards reduced ECMO 0.76, 0.58-1.01; p=0.06, I2=49%) arm compared standard therapy, even though it not significant. Statistical significance achieved all fixed-effects In COVID-19, associated although there ECMO. used conjunction care treatments improved COVID-19 disease. None.

Language: Английский

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Small molecules in the treatment of COVID-19

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 5, 2022

Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies economies. Until now, effective therapeutics against are in high demand. Along with our improved understanding the structure, function, pathogenic process SARS-CoV-2, many small molecules potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition viral proteins such as RdRp M pro , interference host enzymes including ACE2 proteases, blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, NLRP3 pathways, regarded feasible drug development. development treat achieved strategies, computer-aided lead compound design screening, natural product discovery, repurposing, combination therapy. Several representative remdesivir paxlovid proved or authorized emergency use countries. And candidates entered clinical-trial stage. Nevertheless, due epidemiological features variability issues it is necessary continue exploring novel COVID-19. This review discusses current findings for treatment. Moreover, their detailed mechanism action, chemical structures, preclinical clinical efficacies discussed.

Language: Английский

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Impact of COVID-19 on Cardiovascular Disease

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 508 - 508

Published: Feb. 11, 2023

Coronavirus disease 2019 (COVID-19) is a viral infection with the novel severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2). Until now, more than 670 million people have suffered from COVID-19 worldwide, and roughly 7 death cases were attributed to COVID-19. Recent evidence suggests an interplay between cardiovascular (CVD). may serve as yet underappreciated CVD risk modifier, including factors such diabetes mellitus or arterial hypertension. In addition, recent data suggest that previous increase for many entities of extent similarly observed traditional (CV) factors. Furthermore, increased incidence worse clinical outcomes in individuals preexisting been myocarditis, coronary syndrome, heart failure (HF), thromboembolic complications, arrhythmias. Direct indirect mechanisms proposed by which impact CV risk, entry into tissue induction massive systemic inflammatory response. current review, we provide overview literature reporting interaction CVD, review potential underlying this interaction, discuss preventive treatment strategies their interference evaluated since onset pandemic.

Language: Английский

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Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 12(4), P. 305 - 322

Published: Dec. 21, 2023

Language: Английский

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