Efficacy and Safety of Nirmatrelvir/Ritonavir, Molnupiravir, and Remdesivir in a Real-World Cohort of Outpatients with COVID-19 at High Risk of Progression: The PISA Outpatient Clinic Experience

• Published in: Infectious diseases and therapy Vol. 12; no. 1; pp. 257 - 271
• Main Authors: Tiseo, Giusy, Barbieri, Chiara, Galfo, Valentina, Occhineri, Sara, Matucci, Tommaso, Almerigogna, Francesco, Kalo, Jona, Sponga, Pietro, Cesaretti, Mario, Marchetti, Gabriele, Forniti, Arianna, Caroselli, Claudio, Ferranti, Simone, Pogliaghi, Manuela, Polidori, Marina, Fabiani, Silvia, Verdenelli, Stefano, Tagliaferri, Enrico, Riccardi, Niccolò, Suardi, Lorenzo Roberto, Carmignani, Claudia, Batini, Serena, Puccetti, Luca, Iapoce, Riccardo, Menichetti, Francesco, Falcone, Marco
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.01.2023; Springer; Springer Nature B.V
• Subjects: Antiretroviral drugs; Antiviral drugs; Clinics; Complications and side effects; COVID-19; Drugs; Hospitalization; Infectious Diseases; Internal Medicine; Medicine; Medicine & Public Health; Mortality; Observational studies; Original Research; Regression analysis; Risk factors; Ritonavir; Variance analysis; Work experience; COVID-19; Progression; SARS-CoV-2; Remdesivir; Nirmatrelvir/ritonavir; Molnupiravir
• ISSN: 2193-8229; 2193-6382
• DOI: 10.1007/s40121-022-00729-2

Introduction Different antivirals are available for the treatment of outpatients with COVID-19. Our aim was to describe a real-world experience of outpatient management of COVID-19 subjects at high risk of progression. Methods This prospective observational study conducted in the University Hospital of Pisa (January 2022–July 2022) included consecutive COVID-19 outpatients with at least one risk factor for disease progression. Patients received nirmatrelvir/ritonavir, molnupiravir, or 3-day remdesivir, according to the Italian Medicines Agency (AIFA) indications. All patients were followed up until 30 days from the first positive nasopharyngeal swab. The primary endpoint was a composite of death or hospitalization. Secondary endpoints were occurrence of adverse events and a negative test within 10 days from the first positive test. Multivariable analysis was performed to identify factors associated with death or hospitalization. Results Overall, 562 outpatients were included: 114 (20.3%) received molnupiravir, 252 (44.8%) nirmatrelvir/ritonavir, and 196 (34.9%) 3-day remdesivir. The composite endpoint occurred in 2.5% of patients and was more frequent in patients treated with remdesivir (5.1%) compared with molnupiravir (1.8%) or nirmatrelvir/ritonavir (0.8%, ANOVA among groups p  = 0.012). On multivariable Cox regression analysis, presence of ≥ 3 comorbidities, hematological disease, gastrointestinal symptoms, and each-day increment from symptoms onset were factors associated with death or hospitalization, while antiviral treatment was not a predictor. Adverse events occurred more frequently in the nirmatrelvir/ritonavir group (49.2%). Nirmatrelvir/ritonavir compared with remdesivir was associated with a higher probability of having a negative test within 10 days from the first positive one. Conclusion Death or hospitalization did not differ among high-risk COVID-19 outpatients treated with currently available antivirals. Safety and time to a negative test differed among the three drugs.