Funded by the National SciLifeLab-KAW COVID-19 Research Program, Assoc. Professor Volker Lauschke (Karolinska Institutet/Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany) and colleagues from the Imperial College London and Albacete University Hospital, have shown that the Janus kinase (JAK) inhibitor baricitinib significantly reduces 30-day mortality in older adults in long-term care facilities with moderate-to-severe COVID-19 pneumonia. The results are presented in the Journal of the American Geriatric Society.
Baricitinib is a small molecule drug developed for the treatment of rheumatoid arthritis. Early during the COVID-19 pandemic, researchers identified that baricitinib also has an effect against COVID-19. Previous studies have shown that the drug can shorten the disease time and reduce mortality in severe COVID-19, which resulted in the approval of remdesivir plus baricitinib by the Food and Drug Administration (FDA). However, effectiveness in the most vulnerable patient populations remained unexplored.
In March 2021, Volker Lauschke was granted 1 MSEK to study “Organotypic human 3D tissue models for mechanistic studies and antiviral drug development” from the National SciLifeLab-KAW COVID-19 Research Program.
“Baricitinib is associated with a mortality risk reduction for adults older than 70 years hospitalized with COVID-19 pneumonia. The results extend evidence from previous clinical trials, for example the ACTT-2 and COV-BARRIER trials, as they indicate that baricitinib could be an effective treatment also for the most vulnerable, high-risk patient groups”, says Volker Lauschke.
According to the study, treatment with baricitinib results in a significant reduction in 30-day mortality from any cause in patients younger than 70 years by 54%, and by 48% in patients aged 70 or older (p < 0.001). Treatment is moreover associated with an 18.5 % reduction in 30-day absolute mortality risk in patients over 70 years of age.
These results reinforce previous data (links below) by Volker Lauschke and colleagues showing that artificial intelligence-generated hypotheses, followed by rigorous experimental testing in organotypic 3D human tissue models and rapid translation into clinical trials constitutes a powerful framework for the expedited repurposing of drugs.
Publication 1: Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients
Publication 2: JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality