An international team of scientists has found that the arthritis drug baricitinib shows promise for increasing the survival of older adults with COVID-19.
The new research, appearing in the journal Science Advances, lays the groundwork for larger, randomized controlled trials to confirm the initial findings.
Repurposed drugs
Alongside developing an effective and safe vaccine for SARS-CoV-2, scientists are also identifying potential treatments that may help increase the survival chances of people who develop COVID-19.
To do this quickly, scientists have turned to previously available drugs, looking to repurpose them as COVID-19 treatments. Since these medicines already have approval for use, many of the safety tests involved in the development of a novel drug are not required.
However, this is still no small task. There are thousands of potential drugs to search through when identifying those that may be worth testing.
To speed up the process, scientists used artificial intelligence (AI) systems that can rapidly analyze these medicines and determine if they could be effective COVID-19 treatments.
One such drug that artificial intelligence software identified in February 2020 was baricitinib, a medication for adult rheumatoid arthritis.
The software identified this drug because it had two potential mechanisms of action. The first might reduce inflammation, while the second might make it more difficult for the virus to access a person’s cells.
Since these initial findings, baricitinib has been used in clinical settings to treat COVID-19. The scientists behind the present study drew on this initial clinical data and conducted laboratory tests to determine how effective the drug may be as a treatment.
Increased survival
The scientists looked at 83 patients from the University of Pisa, Italy, and the Albacete Hospital, Spain. The participants had an average age of 81 years, with moderate to severe COVID-19, and were given baricitinib as treatment. The research team compared this group to a control group of patients from Italy and Spain, who did not take the drug.
The scientists found that the group who received baricitinib was less likely to need mechanical ventilation, while the patients were less likely to die compared with the control group.
Specifically, 34.9% of the control group either died or needed mechanical ventilation, compared with 16.9% of the patients treated with baricitinib.
Two mechanisms of action
To better understand how baricitinib may causing this beneficial effect, the scientists studied its impact on miniature human organs grown in a laboratory.
This confirmed the initial findings of the AI software: that baricitinib reduces inflammation and makes it more difficult for the virus to access a person’s cells.
A leading cause of death for people with COVID-19 has been acute respiratory distress syndrome. This occurs when a person’s inflammatory response to SARS-CoV-2 goes out of control, damaging respiratory system cells and potentially affecting many other organs in their body.
The scientists found that this inflammatory response can also make it easier for the virus to enter a person’s cells as it replicates itself within their body.
Baricitinib seems to work by reducing both of these reactions, significantly increasing the chances of survival.
According to the study’s co-lead author Prof. Volker Lauschke, associate professor in Personalized Medicine and Drug Development at the Karolinska Institutet in Stockholm, Sweden, “[t]his study confirms what AI predicted, and what we were hearing from patient case reports.”
“For instance, one case involved an 87-year-old severely unwell patient from Foggia, Italy, who showed rapid improvement after being given the drug, whereas her husband and son, who did not receive baricitinib, died.”
“This study has also shone a light on exactly how this drug may protect us at the cellular level. This helps us understand why other types of drugs are proving beneficial, or not beneficial, as we help identify other treatments which may tackle COVID-19.” – Prof. Volker Lauschke
The next step is to confirm the initial findings in larger, randomized controlled trials, which are already proceeding.
For Prof. Justin Stebbing, of the Department of Surgery and Cancer at Imperial College London, United Kingdom, and study co-lead author, “[w]e have seen the top-line results of a randomized study called the Adaptive Covid Treatment Trial-2 announced recently, showing benefits of baricitinib plus remdesivir, compared to remdesivir alone in over 1,000 patients.”
“Other very large trials occurring now include COV-BARRIER, and this will help create a fuller picture of the benefits and side effects of the oral medication (a small number of the patients in our study needed to stop the treatment due to problems with liver function).
“Further trials comparing baricitinib to other drugs in COVID-19 patients would also be helpful in improving outcomes.”
