Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues
We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. How...
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doaj-317a0aabcf094dbdb7c5ca3100acaf4d2021-08-26T14:12:12ZengMDPI AGPharmaceuticals1424-82472021-07-011473873810.3390/ph14080738Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety IssuesMilo Gatti0Eleonora Turrini1Emanuel Raschi2Piero Sestili3Carmela Fimognari4Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum—Università di Bologna, Via Irnerio 48, 40126 Bologna, ItalyDepartment for Life Quality Studies, Alma Mater Studiorum—Università di Bologna, C.so D’Augusto 237, 47921 Rimini, ItalyPharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum—Università di Bologna, Via Irnerio 48, 40126 Bologna, ItalyDepartment of Biomolecular Sciences (DISB), Università degli Studi di Urbino Carlo Bo, Via I Maggetti 26, 61029 Urbino, ItalyDepartment for Life Quality Studies, Alma Mater Studiorum—Università di Bologna, C.so D’Augusto 237, 47921 Rimini, ItalyWe are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered.https://www.mdpi.com/1424-8247/14/8/738coronavirus disease (COVID)-19janus kinase (JAK) inhibitorsbaricitinibruxolitinibreal word evidenceadverse effects |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Milo Gatti Eleonora Turrini Emanuel Raschi Piero Sestili Carmela Fimognari |
spellingShingle |
Milo Gatti Eleonora Turrini Emanuel Raschi Piero Sestili Carmela Fimognari Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues Pharmaceuticals coronavirus disease (COVID)-19 janus kinase (JAK) inhibitors baricitinib ruxolitinib real word evidence adverse effects |
author_facet |
Milo Gatti Eleonora Turrini Emanuel Raschi Piero Sestili Carmela Fimognari |
author_sort |
Milo Gatti |
title |
Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues |
title_short |
Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues |
title_full |
Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues |
title_fullStr |
Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues |
title_full_unstemmed |
Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues |
title_sort |
janus kinase inhibitors and coronavirus disease (covid)-19: rationale, clinical evidence and safety issues |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2021-07-01 |
description |
We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered. |
topic |
coronavirus disease (COVID)-19 janus kinase (JAK) inhibitors baricitinib ruxolitinib real word evidence adverse effects |
url |
https://www.mdpi.com/1424-8247/14/8/738 |
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