Le Lagevrio® (Molnupiravir) (MSD) has been included by the WHO under conditions, in the possible treatments against COVID-19. But in France, while it is authorized in the United Kingdom, Italy and the United States, the drug has received a unfavorable opinion of the High Authority for Health. However, molnupiravir was the first oral antiviral to feature in COVID-19 treatment guidance, despite very limited safety data and therefore conditional on active pharmacovigilance.
The Paxlovid® (nirmatrelvir/ritonavir) (Pfizer), documented as effective against the Omicron variantis authorized in France for adults with COVID-19 not requiring oxygen therapy and at high risk of progression to a severe form of the disease.
The antivirals are always more useful before the disease becomes serious
“Because antiviral drugs may be more useful in milder forms of the disease”says lead author Dr. Tyler Pitre, of the Department of Internal Medicine at McMaster University, “our review of the literature fills an important gap”. Because data remains limited on these 2 antivirals and most trials have so far focused on patients with severe or critical COVID-19. The Canadian team therefore conducted a systematic review and meta-analysis to better assess the efficacy of these drugs in the treatment of non-severe COVID-19 disease.
The study identified 41 trials involving a total of 18,568 patients with non-severe COVID-19, most of whom were between 36.5 and 65.5 years old. Analysis reveals that compared to standard care or placebo,
- nirmatrelvir-ritonavir reduced the risk of hospitalization (46.2 fewer admissions per 1,000 patients);
- molnupiravir “probably” reduces the risk (16.3 fewer admissions per 1,000 patients).
According to the authors, the implications are important for health systems and for clinical guidelines. The results also suggest that nirmatrelvir-ritonavir may be superior to molnupiravir for some outcomes, with implications, too, for drug supply.
Finally, as several of the trials included in the analysis were conducted in unvaccinated patients infected with the Delta variant, the researchers call for continued research to
“rapidly generate evidence in a context of ever-changing viral circulation”.