Close Up Of Pills Pouring Out Of A Prescription Medication Bottle; Image credit: Getty Images

The oral antiviral drugs molnupiravir and nirmatrelvir–ritonavir (Paxlovid) appear to reduce the risk of death from COVID-19 in patients with mild to moderate disease and may be most useful in that population, according to the authors of a comprehensive review of studies.

Investigators from McMaster University in Ontario, Canada, examined data from 41 randomized trials involving more than 18,000 patients. The studies compared antiviral treatments, standard care or placebo in adult patients through April 25, 2022.

They found that molnupiravir and Paxlovid likely reduce risk of death and hospital admission without increasing adverse events. In addition, Paxlovid is also likely more effective than molnupiravir at reducing risk of hospital admission. Notably, although data on Paxlovid is limited, the evidence has “consistently shown” reduced hospital admissions and deaths, they added. 

Remdesivir, which studies included as a comparison drug, may reduce risk of hospital admission and the need for mechanical ventilation, but this finding has low certainty, reported Tyler Pitre, MD, and colleagues.

More useful in milder disease

The review’s results also address an important evidence gap on COVID-19 antiviral drugs, Pitre and colleagues wrote. 

Initial studies of antiviral COVID-19 treatments took place in patients with severe and critical disease. Based on the new analysis, the authors theorize that these drugs are most useful in non-severe disease. That’s because non-severe disease is driven by viral proliferation — which the antivirals fight — rather than inflammatory response, which is the factor driving severe disease, they wrote.

Paxlovid and molnupiravir were granted emergency use authorization by the Food and Drug Administration in December 2021. Paxlovid is the preferred therapy for managing non-hospitalized adults with COVID-19, according to the National Institutes of Health’s COVID-19 Treatment Guidelines

The current study was published July 25 in the Canadian Medical Association Journal.

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