Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system
Dr Joseph A Lewnard, PhD John M Mclaughlin, Debbie Malden, Vennis Hong, PhD, L Jodar PhD Laura Puzniak, MD Bradley K Ackerson, Bruno J Lewin, PhD Jeniffer S Kim, Sally F Shaw, Harpreet Takhar, Luis Jodar, Sara Y Tartof
The Lancet Infectious Diseases, doi:10.1016/s1473-3099(23)00118-4
Background In the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mildto-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA. Methods In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2. Findings 7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75•2%) treatment recipients and 84 657 (67•1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53•6% (95% CI 6•6-77•0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79•6% (33•9-93•8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89•6% (50•2-97•8). Interpretation In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test.
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