Corticosteroids
Maria G. Tanzi, PharmD
Additional evidence from randomized controlled trials and a meta-analysis further support the role of systemic corticosteroids in the treatment of patients with severe COVID-19 infection, with the World Health Organization (WHO) providing a strong recommendation for their use in patients with severe and critical infections.
“With the consistent signal across more than four randomized controlled trials and a meta-analysis, it is pretty clear that corticosteroids are beneficial for the sickest patients with COVID-19,” said Todd W. Rice, MD, MSc, associate professor of medicine, division of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center. “They reduce mortality, which is the ultimate benefit, and they really are the new standard of care for treating hospitalized patients with COVID-19 [who require] oxygen.”
Additional data builds on RECOVERY findings
The results of the RECOVERY trial released in June showed that use of dexamethasone resulted in lower 28-day mortality among hospitalized patients with COVID-19 and prompted the early termination and analyses of additional trials evaluating the use of corticosteroids in this setting.
In its September 2 issue, JAMA published results from three randomized controlled trials and a prospective meta-analysis from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. The results of the meta-analysis, which included data from 7 randomized clinical trials of 1703 critically ill patients with COVID-19, showed that 28-day all-cause mortality was lower among patients who received corticosteroids compared with those who received usual care or placebo. The effects on mortality were similar for dexamethasone and hydrocortisone, and there was no suggestion that they increased risk of serious adverse events.
Further WHO analyses, conducted during the development of its guidance document on the use of corticosteroids for COVID-19, found that systemic corticosteroids probably reduce 28-day mortality in patients with critical COVID-19 and also in those with severe disease.
In addition, systemic corticosteroids probably reduce the need for invasive mechanical ventilation.
In contrast, WHO found that the data do not support the use of systemic corticosteroids in those with nonsevere disease, as they may actually increase the risk of death.
WHO, NIH recommendations
In early September, WHO released its living guidance on the use of corticosteroids for COVID-19. The guidance makes a strong recommendation for I.V. or oral systemic use of corticosteroid therapy for patients with severe and critical COVID-19 infections (e.g., 6 mg of I.V. or oral dexamethasone given daily, or 50 mg of I.V. hydrocortisone given every 8 hours for 7 to 10 days). Based on the data, WHO also gave a conditional recommendation not to use corticosteroid therapy in patients with nonsevere COVID-19. Access the full guidance at https://apha.us/WHOcorticosteroids.
The National Institutes of Health (NIH) has also released a guide on prophylaxis use, testing, and management of patients with COVID-19, including the use of corticosteroids. NIH also recommends dexamethasone, 6 mg per day for up to 10 days or until hospital discharge, whichever comes first, for patients who are mechanically ventilated and those who require supplemental oxygen. Additionally, NIH lists alternative corticosteroids such as prednisone, methylprednisolone, or hydrocortisone as options when dexamethasone is not available. Consistent with the WHO guidance, NIH recommends against using dexamethasone for the treatment of COVID-19 in patients who do not require supplemental oxygen. The NIH guide is available at https://apha.us/NIHcorticosteroids.
“It appears that the benefit is a class effect, meaning that any corticosteroid probably is beneficial—so this represents an inexpensive and readily available treatment that improves survival in patients with COVID-19,” said Rice. “We hardly ever get those results, so it is a very big deal.”