SynthesisJournal of general internal medicine2026
Effectiveness of Nirmatrelvir/Ritonavir for Outpatients in the Era of Omicron, Vaccination, and Previous Infection: A Meta-analysis.
Synthesis in Journal of general internal medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSince the benefit of nirmatrelvir-ritonavir (N-R) may have changed in contemporary patients, we assessed the effectiveness of N-R for preventing hospitalization and death among outpatients with COVID-19 in the Omicron era.
methodsThis was a meta-analysis of cohort studies comparing rates of hospitalization and/or mortality in outpatients treated with N-R compared with untreated patients. Analysis was limited to studies conducted since December 2021 that performed an adjusted multivariate analysis. Quality was assessed using the Newcastle-Ottawa Scale. Summary estimates of adjusted relative risks (aRR) with 95% confidence intervals (CI) and prediction intervals (PI) were calculated overall and for prespecified subgroups. Heterogeneity was summarized visually and with τ and 95% PIs. Absolute effects were estimated by applying pooled aRRs to baseline risks to obtain absolute risk reductions (ARRs) and numbers needed to treat (NNTs).
resultsForty-seven studies (10,791,211 patients) were included. Pooled aRRs were 0.54 (95% CI, 0.43-0.68) for all-cause hospitalization and 0.45 (0.36-0.56) for COVID-19 hospitalization. Pooled RRs were 0.30 (0.23-0.39) for all-cause mortality and 0.43 (0.32-0.59) for COVID-19 mortality. PIs were < 1.0 for COVID-19 hospitalization (0.21-0.96), all-cause mortality (0.11-0.83), and any mortality (0.13-0.88), indicating likely benefit in future studies in similar settings. Subgroup analyses showed larger effects earlier in the Omicron period for hospitalization (RR 0.46 vs 0.68; p = 0.0049) and the composite outcome (0.45 vs 0.68; p = 0.0078), and a smaller mortality reduction among immunocompromised patients (RR 0.26 vs 0.11; p = 0.034). The estimated NNT to prevent a COVID-19 hospitalization for patients at low risk (0.16%), moderate risk (2.2%), and high risk (8.9%) of hospitalization based on a validated risk score were 1148, 84, and 20 respectively. DISCUSSION: N-R is associated with reduced hospitalization and death. Absolute risk reductions of hospitalization are small in low-risk patients but clinically meaningful in moderate- and high-risk patients.
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