From today, baricitinib – an anti-inflammatory treatment for rheumatoid arthritis– will be investigated in the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial. This is the world’s largest clinical trial of treatments for patients hospitalised with COVID-19, taking place in 177 hospital sites across the UK and with over 33,000 patients recruited so far.
Professor Peter Horby, from the Nuffield Department of Medicine at the University of Oxford, UK, co-Chief Investigator of the RECOVERY trial, said ‘The COVID-19 pandemic is far from over, in fact it is getting worse, and we need to keep pushing to find better treatments. The fatality rate in patients hospitalised with COVID-19 remains far too high and I believe we can and must bring it down. Baricitinib will be the tenth potential COVID-19 treatment to be tested through RECOVERY and we will continue testing new drugs as fast as we possibly can.’
As an anti-inflammatory, baricitinib may block the signalling activity of cytokine molecules which contribute to the hyper-inflammatory state seen in severe COVID-19. It is thought that baricitinib may act also have some anti-viral activity.
There is some clinical trial evidence that baricitinib may be beneficial against COVID-19. The Adaptive Covid-19 Treatment Trial (ACTT-2), a randomised clinical trial involving over 1,000 patients with moderate to severe COVID-19, tested baricitinib with remdesivir against remdesivir with a placebo. This concluded that baricitinib with remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among COVID-19 patients, particularly those receiving oxygen or non-invasive ventilation. Although the survival rate was numerically better in the baricitinib treated group, the numbers were too small to provide a clear answer. The ACTT-2 trial did not look at the effect of baricitinib in addition to corticosteroids (steroids), which is now standard of care for severe COVID-19 worldwide.
Professor Martin Landray, from the Nuffield Department of Population Health at the University of Oxford, who co-leads the RECOVERY trial, explained ‘Inflammation is a fundamental feature of COVID-19 and the RECOVERY trial has already found that one anti-inflammatory drug, dexamethasone, can reduce deaths in the most severely ill patients with COVID-19. Baricitinib is widely used to treat rheumatoid arthritis. By including baricitinib in the RECOVERY trial, we will be able to generate robust evidence on whether it helps tackle the worst consequences of COVID-19.’
It is anticipated that at least 2500 patients recruited to the RECOVERY trial will be randomly allocated to receive baricitinib plus usual standard-of-care, and results will be compared with at least 2500 patients who receive usual standard-of-care on its own. The dosage used will be a 4mg tablet once daily. The main aim is to assess the whether barictinib reduces the risk of death among patients admitted to hospital with COVID-19. The trial will also be able to assess whether the treatment shortens the length of hospital stay or reduces the need for a mechanical ventilator. Depending on recruitment rates, it is likely to be several months before the results are available.
The decision to add baricitinib to the trial was made by the University of Oxford researchers and trial steering committee leading the trial in conjunction with the Chief Medical Officer, following a recommendation by the UK COVID-19 Therapeutics Advisory Panel.
The other treatments currently being investigated in the RECOVERY trial are:
- Regeneron’s antibody cocktail (a combination of monoclonal antibodies directed against coronavirus)
- Aspirin (commonly used to thin the blood)
- Colchicine (a commonly used anti-inflammatory drug).
The RECOVERY Trial is conducted by the registered clinical trials units with the Nuffield Department of Population Health in partnership with the Nuffield Department of Medicine. The trial is supported by a grant to the University of Oxford from UK Research and Innovation/National Institute for Health Research (NIHR) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth & Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, and NIHR Clinical Trials Unit Support Funding.
The RECOVERY trial involves many thousands of doctors, nurses, pharmacists, and research administrators at 177 hospitals across the whole of the UK, supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, the Secure Anonymised Information Linkage at University of Swansea, and the NHS in England, Scotland, Wales and Northern Ireland.