The World Health Organization (WHO) has released the 11th update to their living guideline on treatments for COVID-19 infection. The updated guidance includes new recommendations on remdesivir, concomitant therapy with corticosteroids and interleukin (IL)-6 receptor blockers plus Janus kinase (JAK) inhibitors, and neutralizing monoclonal antibodies. The update, which was created by the WHO’s guideline development group (GDG) based on assessment of new evidence, was published in BMJ.
A conditional recommendation was made for the use of remdesivir in patients with severe disease but against its use in those with critical disease.
The GDG considered data from a meta-analysis conducted among 7643 patients with severe or critical COVID-19 infection in issuing these recommendations.
For patients with severe disease, treatment with remdesivir was associated with decreased risk of both mortality (odds ratio [OR], 0.89; 95% CI, 0.78-1.02) and the need for mechanical ventilation (OR, 0.87; 95% CI, 0.77-0.99).
For patients with critical illness, treatment with remdesivir was associated with an insignificant decrease in the risk of both mortality (OR, 1.15; 95% CI, 0.89-1.51) and the need for mechanical ventilation (OR, 0.97; 95% CI, 0.61-1.54). There also was an uncertain effect of remdesivir on time to symptom improvement among patients with critical disease.
Overall, remdesivir was well tolerated and associated with low risk for adverse events.
JAK Inhibitors With Corticosteroids Plus IL-6 Receptor Blockers
A strong recommendation was made for the use of combination therapy consisting of JAK inhibitors with corticosteroids plus IL-6 receptor blockers in patients with severe or critical disease.
According to the GDG, concomitant therapy with baricitinib plus either tocilizumab or sarilumab may be combined with corticosteroids for the treatment of patients with severe or critical COVID-19 infection. This recommendation follows clinical trial evidence showing that baricitinib had an incremental survival benefit among patients receiving corticosteroids in combination with IL-6 receptor blockers.
Neutralizing Monoclonal Antibodies
A strong recommendation was made against the use of the neutralizing monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with nonsevere COVID-19 infection.
According to the GDG, available evidence shows that sotrovimab lacks in vitro neutralization activity against the currently circulating SARS-CoV-2 Omicron variant and its subvariants. The group noted similar findings in regard to its recommendation against the use of casirivimab-imdevimab.
The GDG plans to issue recommendations on the use of anticoagulants in the next iteration of this living guideline.
“Vaccines are linked to limiting hospitalisations, but limitations in global access and residual uncertainties remain regarding the duration of protection following vaccination or natural infection, and their efficacy against emerging SARS-CoV-2 variants and subvariants,” the GDG noted. “Therefore,” the group concluded, “the potential for drugs to treat people infected with [COVID-19] remains of interest.”
Agarwal A, Rochwerg B, Lamontagne F, et al. A living WHO guideline on drugs for covid-19. BMJ 2020;370:m3379. doi:10.1136/bmj.m3379