January 13, 2022

expert reaction to WHO recommending two drugs, sotrovimab and baricitinib, to treat patients with COVID-19

A new clinical practice guideline from the WHO Guideline Development Group recommending baricitinib and sotrovimab as COVID-19 treatments has been published in the BMJ.

Prof Sir Martin Landray, Professor of Medicine & Epidemiology, Oxford Population Health, University of Oxford, said:

“The WHO guideline has been updated to recommend two new drugs:

“Sotrovimab (a monoclonal antibody) for use in patients who have not been admitted to hospital.  Sotrovimab is a monoclonal antibody that neutralises the spike antibody.  It is developed and marketed by GSK and Vir Biotechnology.  Unlike other monoclonal antibodies, it appears to be effective against the omicron variant.  It is already approved for use and available in the UK for patients in the community who are at high risk of requiring hospitalisation.  We do not currently know if it will be effective in shortening hospital stay, reducing the need for a mechanical ventilator, or improving survival for sicker patients – those who have been admitted to hospital because of COVID-19.  Hence we are studying this as part of the RECOVERY trial.

“Baricitinib is a drug normally used for patients with rheumatoid arthritis.  It work by dampening down the immune system, which can be over-active in patients with severe COVID-19 and lead to lung damage requiring oxygen or mechanical ventilation and precipitate death.  There have been encouraging results in previous trials involving around 3600 patients admitted to hospital with severe COVID-19.  Those data suggest that treatment with barictinib may reduce the risk of death by about one-third.  However, the story may not be so clear-cut – the RECOVERY trial randomised over 8000 patients to barictinib vs. usual NHS care alone.  Hence the RECOVERY trial contains more than twice as much information on the effects of baricitinib as all the previous trials put together.  Enrolment closed at the end of December and follow-up of all patients will be complete later this month.  The results are not yet known (by me or anyone else).  However, it would in my view be wise to wait until the results are available in a few weeks’ time before rushing to use baricitinib as an alternative to drugs with proven efficacy such as tocilizumab.”

Prof Athimalaipet Ramanan, Professor of Paediatric Rheumatology, University of Bristol, said:

“The strong recommendation from WHO comes at much needed time as many low- and middle-income countries continue to struggle with the pandemic.  Baricitinib has been shown in randomised controlled trials to be effective in adults with moderate to severe disease including those needing ventilation.  The short half-life, oral administration and lower cost make this more attractive across the world compared to Tocilizumab (the other agent shown to be effective in a similar setting).”

Prof Penny Ward, Independent Pharmaceutical Physician, and Visiting Professor in Pharmaceutical Medicine at King’s College London, said:

“The BMJ today is drawing our attention to the most recent release of the WHO’s living guideline on COVID therapeutics.  This is the eighth version of the guideline and updates prior recommendations to include the use of bariticinib as a possible oral alternative to tocilizumab in critically ill hospitalised patients and sotrovimab as a possible early treatment to prevent disease progression in high risk patients with mild-moderate disease in the community.

“The committee have not yet addressed the potential use of oral antivirals and this guideline considers only treatment of disease, there being a separate living guideline addressing possible use of medicines other than vaccines for the prevention of disease.  The panel forming the guidance is drawn from the expert community in multiple countries across the globe thus including perspectives from regions with varying healthcare resources.  In addition the group makes recommendations taking into account individual patient perspectives alongside resource implications, acceptability, feasibility, equity, and human rights.

“The main issue with this version of the guideline is its silence concerning the for potential community use of oral antiviral medications which are now approved for use in multiple countries; presumably we can expect version 9 in the near future given their recommendation for use of sotrovimab in this context despite this requiring IV administration.

“The guideline also fails to reevaluate the position of the first approved antiviral, remdesivir, a three day course of which was shown to prevent disease progression when given within the first 5 days following onset of symptoms.  Generally speaking patients in the community might be expected to prefer early treatment to prevent more serious disease rather than waiting until hospital care is required, at which point the proportion of patients dying will increase.

“As the emergence of the omicron strain has reminded us, the emergence of a vaccine resistant strain is an ever present concern, for which alternative approaches may be required, not only to treat the sick but also to protect vulnerable contacts.  Amalgamating this guideline with its sister guideline on chemoprophylaxis might now be appropriate alongside a faster timeframe to the incorporation of evidence so that the guidelines keep pace with the regulators who have been approving products for clinical use some months before advice on clinical use is updated.”

‘A living WHO guideline on drugs for covid-19’ by Arnav Agarwal et al. was published in the BMJ at 23:01 UK time on Thursday 13 January 2022.

DOI: 10.1136/bmj.m3379

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Sir Martin Landray: “Professor of Medicine & Epidemiology, Oxford Population Health

Co-lead RECOVERY trial

RECOVERY receives funding from MRC, NIHR and Wellcome. GSK/Vir are providing sotrovimab. Roche provided tocilizumab.”

Prof Athimalaipet Ramanan: “Part of trial steering group/author of study of Baricitinib in COVID. Involved in trial of Tocilizumab in COVID (in India) and part of WHO led analysis of Tocilizumab for COVID. Consulting/Advisor to Eli Lilly and Roche.”

Prof Penny Ward: “I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development. Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases. Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”