Real-World Effectiveness of Nirmatrelvir-Ritonavir and Its Acceptability in High-Risk COVID-19 Patients

Background: Nirmatrelvir-ritonavir is highly effective in preventing severe coronavirus disease 2019 (COVID-19) in high-risk patients with mild-to-moderate severity. However, real-world performance data are limited, and the drug is not so acceptable to the COVID-19 patients at high risk who need it in Korea. Methods: To evaluate the effectiveness of nirmatrelvir-ritonavir, we conducted a propensity score-matched retrospective cohort study on patients with mild-to-moderate COVID-19 at high risk for a severe disease who were hospitalized at four hospitals in South Korea from February 2022 to April 2022. A total of 236 patients in the treatment group (administered nirmatrelvir-ritonavir) and 236 in the matched control group (supportive care only) were analyzed for the primary outcome, i.e., the time to oxygen support-free survival. The secondary outcome was a composite result of disease progression. The reason for not prescribing nirmatrelvir-ritonavir to the indicated patients was also investigated. Results: The treatment group showed significantly longer oxygen support-free survival than the matched control group (adjusted hazard ratio [aHR], 0.07, 95% confidence interval [CI], 0.01–0.31, P < 0.001). Multivariate Cox regression analysis showed that age (aHR, 1.03, 95% CI, 1.00–1.07), National Early Warning Score-2 at admission (aHR, 1.36, 95% CI, 1.08–1.71), nirmatrelvir-ritonavir treatment, female sex (aHR, 0.37, 95% CI, 0.15–0.88), and time from symptom onset to admission (aHR, 0.67, 95% CI, 0.48–0.95) were significantly associated with oxygen therapy. However, none of the factors were related to the composite outcome. In the unmatched control group, 19.9% of 376 patients had documented explanations for nirmatrelvir-ritonavir non-prescription, and 44.0% of these were due to contraindication criteria. In the treatment group, 10.9% of patients discontinued the medication primarily because of adverse events (71.4%), with gastrointestinal symptoms being the most common (50.0%). Conclusion: Nirmatrelvir-ritonavir treatment significantly reduced oxygen therapy requirements in high-risk patients with COVID-19 during the omicron variant surge in South Korea. Physicians are encouraged to consider the active use of nirmatrelvir-ritonavir and to be watchful for gastrointestinal symptoms during medication.