Baricitinib set to join the Covid-19 therapeutic arsenal?

Gudu, T.; Stober, Carmel B.; Cope, Andrew; Cheriyan, Joseph; Galloway, James; Wilkinson, Ian B.; Kostapanos, Michael S.; Jayne, David; Hall, Frances

doi:10.1093/rheumatology/keab061

Cited by 7 publications

(8 citation statements)

References 7 publications

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“…Baricitinib has a strong effect in reducing IL-6 and other proinflammatory cytokines in patients with COVID-19 infection and other diseases[24, 25]. The antiviral effect sustained its second mechanism of action, decreasing the rate of endocytosis of the virus by inhibiting the AP2-associated kinase and cyclin G-associated kinase that mediates the cellular membrane’s coating process after the virus binds the spike protein of the angiotensin-converting enzyme[28, 29].…”

Section: Discussionmentioning

confidence: 99%

“…Serious adverse events related to the drug were notably absent, and there was no instance of discontinuation of baricitinib due to side effects in the case group. Long-term use of baricitinib is associated with increased thrombosis incidence and 12 viral/bacterial superinfections in patients with resistant Rheumatoid arthritis [28]. The safety profile of Baricitinib was assessed in the ACTT-2 trial, and the incidence of thrombosis and bacterial infections for patients with COVID-19 infections were similar in the baricitinib and placebo-group.…”

Section: Discussionmentioning

confidence: 99%

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Combination of Baricitinib plus Remdesivir and Dexamethasone improves time to recovery and mortality among hospitalized patients with severe COVID-19 infection

Gutiérrez¹,

Shah²,

Afzal³

et al. 2022

Preprint

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BackgroundThere seems to be a gap in the therapeutic options for severe Covid-19 pneumonia. Though the beneficial effect of combination treatment with baricitnib and remdesivir in accelerating clinical status improvement is described, the impact of the triple therapy with baricitinib + remdesivir/dexamethasone is not known.MethodsA retrospective observational study comparing the effect of baricitinib plus standard treatment (remdesivir and dexamethasone) with standard therapy in patients requiring ≥ 5 L/min O2 was conducted. The primary outcome was to compared time to recovery in both groups, and the secondary outcomes was to determine mortality rate at discharge.ResultsOf 457 patients hospitalized during the study period, 51 patients received standard treatment while 88 patients received baricitinib plus standard treatment. In baricitinib group, the rate ratio of recovery was 1.28 (95%CI 0.84-1.94, p=0.24) with a reduction in median time to recovery of 3 days compared to standard treatment group. Subgroup analysis based on Ordinal Scale showed reduction in median time to recovery by 4 and 2 days with rate ratio of recovery of 2.95 (1.03-8.42, p =0.04) and 1.80 (1.09-2.98, p=0.02) in Ordinal Scale 5 and 6 respectively. No benefit was found in the Ordinal Scale 7 subgroup. An overall decrease in rate (15.9% vs 31.4% p=0.03) a likelihood (OR 0.41, 95%CI 0.18-0.94, p=0.03) of mortality was observed in the baricitinib group. Bacteremia and thrombosis were noted in the Baricitinib group, but comparable with the Standard of care group.ConclusionBaricitinib with standard therapy reduced time to recovery and offer mortality benefit in patients with severe COVID-19 pneumonia.”

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Combination of Baricitinib plus Remdesivir and Dexamethasone improves time to recovery and mortality among hospitalized patients with severe COVID-19 infection

Gutiérrez¹,

Shah²,

Afzal³

et al. 2022

Preprint

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“…Among the kinase inhibitors group, JAK inhibitors have shown antiviral action, targeting cellular enzymes exploited by viruses for cell entry [ 77 , 78 ] and relieving the inflammation induced by viral infections, such as COVID-19, characterized by cytokine storm [ 79 ].…”

Section: Repositioning Applications Of Ruxolitinib: From Autoinflamma...mentioning

confidence: 99%

New Applications of JAK/STAT Inhibitors in Pediatrics: Current Use of Ruxolitinib

et al. 2022

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Janus kinases (JAK) are a family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) that transduce cytokine-mediated signals through the JAK–STAT metabolic pathway. These kinases act by regulating the transcription of specific genes capable of inducing biological responses in several immune cell subsets. Inhibition of Janus kinases interferes with the JAK–STAT signaling pathway. Besides being used in the treatment of cancer and inflammatory diseases, in recent years, they have also been used to treat inflammatory conditions, such as graft-versus-host disease (GVHD) and cytokine release syndrome as complications of allogeneic hematopoietic stem cell transplantation and cell therapy. Recently, the FDA approved the use of ruxolitinib, a JAK1/2 inhibitor, in the treatment of acute steroid-refractory GVHD (SR-aGVHD), highlighting the role of JAK inhibition in this immune deregulation. Ruxolitinib was initially used to treat myelofibrosis and true polycythemia in a high-dose treatment and caused hematological toxicity. Since a lower dosage often could not be effective, the use of ruxolitinib was suspended. Subsequently, ruxolitinib was evaluated in adult patients with SR-aGVHD and was found to achieve a rapid and effective response. In addition, its early low-dose use in pediatric patients affected by GVHD has proved effective, safe, and reasonably preventive. The review aims to describe the potential properties of ruxolitinib to identify new therapeutic strategies.

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“…JAKi interfere with the Janus Kinase (JAK)-signal transducers and activators of transcription (STAT) pathways involved in processes such as immunity, cell division, cell death, and tumor formation. [ 9 ]The JAK-STAT pathways transduce signals through >50 cytokine and growth factor receptors. In addition, JAK 1,2-selective inhibitors (e.g.…”

mentioning

confidence: 99%

“…[ 8 ]In addition, JAKi may paradoxically enhance the anti-viral response through various mechanisms including (1) reduction of interferon-mediated ACE2 upregulation or (2) limitation of lymphopenia arising from over-dominance of myelopoiesis in excessive acute-phase response, and (3) reducing activated T-lymphocytes and NK cells which may limit cytotoxic tissue damage. [ 9 ]…”

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confidence: 99%

What's new in critical illness and injury science? An evidence-based analysis of the impact of Janus Kinase inhibitors on 28-day mortality in patients admitted with COVID-19

Miller¹,

D'Silva²

2021

Int J Crit Illn Inj Sci

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Baricitinib set to join the Covid-19 therapeutic arsenal?

Cited by 7 publications

References 7 publications

Combination of Baricitinib plus Remdesivir and Dexamethasone improves time to recovery and mortality among hospitalized patients with severe COVID-19 infection

Combination of Baricitinib plus Remdesivir and Dexamethasone improves time to recovery and mortality among hospitalized patients with severe COVID-19 infection

New Applications of JAK/STAT Inhibitors in Pediatrics: Current Use of Ruxolitinib

What's new in critical illness and injury science? An evidence-based analysis of the impact of Janus Kinase inhibitors on 28-day mortality in patients admitted with COVID-19

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