Effectiveness of nirmatrelvir‐ritonavir on severe outcomes of COVID‐19 in the era of vaccination and Omicron: An updated meta‐analysis

Abstract

Nirmatrelvir‐ritonavir (NR) was approved to treat SARS‐CoV‐2 positive outpatients at high risk of progression to severe disease, based on a randomized trial in unvaccinated patients. Effectiveness in vaccinated patients and against Omicron has not yet been confirmed by clinical trial data, but a recent meta‐analysis suggested good real‐world effectiveness based on 12 studies. We updated this meta‐analysis by searching Medline and Embase databases for studies assessing effectiveness of NR on mortality, hospitalization, composite outcome of hospitalization and/or death, and progression to severe disease, published between October 1, 2022 and May 22, 2023. Random effects meta‐analysis and subgroup analysis for vaccinated patients was performed. A total of 32 studies were included in the meta‐analysis. Pooled RR for the effect of NR on mortality, hospitalization, hospitalization and/or mortality, and progression to severe disease were 0.36 (95% confidence interval [CI]: 0.25−0.52), 0.43 (CI: 0.37−0.51), 0.52 (CI: 0.45−0.61) and 0.54 (CI: 0.41−0.73), respectively. A subgroup analysis on vaccinated patients indicated lower effectiveness of NR on mortality (RR: 0.55, CI: 0.45−0.68), but similar effectiveness for hospitalization, hospitalization and/or mortality, or progression to severe disease (RR: 0.52, 0.58, and 0.66, respectively). This updated meta‐analysis robustly confirms the protective effects of NR on severe COVID‐19 outcomes.