Evaluation of nirmatrelvir/ritonavir treatment for COVID-19 on health-related outcomes: a global economic value systematic literature review.

Clinical Snapshot

Key Findings

• P Value: Not applicable — narrative economic systematic literature review

• Effect Size: Directional: NMV/r associated with reductions in hospitalisations and deaths, increases in QALYs, and reduced long COVID complications. No pooled quantitative effect size reported.

• Primary Outcome: Health-related outcomes associated with NMV/r treatment across 33 included economic evaluations, including hospitalisations (reported in 20 studies), deaths (18 studies), QALYs (18 studies), and long COVID complications

• Nnt Or Sensitivity: Not reported in abstract. ICER values and willingness-to-pay thresholds from individual studies not summarised. NNT not calculable from available data.

• Confidence Interval: Not reported — no meta-analytic pooling performed

Clinical Application

NMV/r requires initiation within 5 days of symptom onset, necessitating rapid access pathways. Significant drug-drug interactions (particularly with calcineurin inhibitors, anticoagulants, statins, and antiretrovirals) require careful medication reconciliation. Renal dose adjustment is required for eGFR <60 mL/min/1.73m². These practical constraints are not addressed in the economic review. Nirmatrelvir/ritonavir (Paxlovid) is TGA-approved and listed on the PBS for eligible high-risk COVID-19 patients in Australia (PBS item numbers for specific eligibility criteria including age ≥70 years, immunocompromised status, and other high-risk conditions). The RACGP has published guidance on prescribing NMV/r in primary care. Australian HTA context (PBAC assessment) is relevant — the PBAC has previously evaluated NMV/r, and this eSLR may inform future resubmissions or listing extensions. The finding of cost-effectiveness across high-income country settings is broadly consistent with Australian economic analyses. However, current PBS eligibility criteria and the evolving severity profile of circulating Omicron subvariants in Australia should be considered when applying these findings. Adults with mild to moderate COVID-19 at high risk of progression to severe disease, including elderly patients, immunocompromised individuals, and those with significant comorbidities. The review's high-income country focus is broadly applicable to Australian clinical practice.

Abstract

AIMS: Nirmatrelvir/ritonavir (NMV/r)i is an antiviral drug indicated for the treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk of progressing to severe disease. We performed an updated economic systematic literature review (eSLR) of NMV/r to build upon evidence reported in our previous eSLR and additionally examine the health-related outcomes associated with NMV/r and any potential effect of long COVID. METHODS: A systematic search of Embase, PubMed, Cochrane, and EconLit and of conference and health technology assessment agency websites was performed to identify economic analyses published between January 2022 and October 2025. RESULTS: Of the 33 included economic evaluations, most were cost-utility analyses (n = 16) and used an analysis of a short-term decision tree with a long-term Markov model (n = 11). Several types of health-related endpoints were reported by studies, with most including hospital-related endpoints (n = 20), quality-adjusted life-years (QALYs) (n = 18), and death-related endpoints (n = 18). Positive health-related outcomes were associated with NMV/r treatment, including reductions in hospitalizations and deaths and an increase in QALYs. NMV/r treatment was also associated with a reduced number of patients with long COVID complications. LIMITATIONS: Most studies were conducted in high-income countries, were based on different COVID-19 variants, and were limited in data on the long COVID population. CONCLUSION: In addition to monetary benefits, NMV/r provides short-term and long-term health-related benefits to patients with mild to moderate COVID-19. This study provides further support for NMV/r as a cost-effective treatment option.

References

1. 1.Mugwagwa, T., Marcano Belisario, J., Hartley, L., Phan, N. T. N., & Mokgokong, R. (2026). Evaluation of nirmatrelvir/ritonavir treatment for COVID-19 on health-related outcomes: a global economic value systematic literature review. Journal of Medical Economics. https://doi.org/10.1080/13696998.2026.2695551