Comparative Effectiveness of Outpatient COVID-19 Therapies in Solid Organ Transplant Recipients

Background: Multiple outpatient therapies have been developed for COVID-19 in high-risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population. Methods: We performed a retrospective cohort study using de-identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age >= 18 years, diagnosed with COVID-19 between January 2022 and December 2023, and underwent SOT prior to COVID-19. The primary outcome was 30-day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables. Results: 4192 SOT recipients with COVID-19 were identified. 1403 received an outpatient COVID-19 therapy, including anti-spike monoclonal antibodies (N = 748, 53.3%), molnupiravir (N = 327, 23.3%), ritonavir-boosted nirmatrelvir (N = 217, 15.5%), or remdesivir (N = 141, 10.0%). In weighted analysis compared to no treatment, anti-spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28-0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36-0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25-0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50-1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti-spike monoclonal antibodies. Conclusions: Outpatient COVID-19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30-day hospitalization, except for remdesivir. The choice of outpatient COVID-19 therapy in SOT recipients should primarily account for patients' individual circumstances and drug-drug interactions rather than differential therapeutic efficacy.