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. 2023 Jan;12(1):257-271.
doi: 10.1007/s40121-022-00729-2. Epub 2022 Nov 28.

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

Giusy Tiseo  1 , Chiara Barbieri  2 , Valentina Galfo  2 , Sara Occhineri  2 , Tommaso Matucci  2 , Francesco Almerigogna  2 , Jona Kalo  2 , Pietro Sponga  2 , Mario Cesaretti  2 , Gabriele Marchetti  2 , Arianna Forniti  2 , Claudio Caroselli  2 , Simone Ferranti  2 , Manuela Pogliaghi  2 , Marina Polidori  2 , Silvia Fabiani  2 , Stefano Verdenelli  2 , Enrico Tagliaferri  2 , Niccolò Riccardi  2 , Lorenzo Roberto Suardi  2 , Claudia Carmignani  3 , Serena Batini  4 , Luca Puccetti  4 , Riccardo Iapoce  2 , Francesco Menichetti  2 , Marco Falcone  5
Affiliations

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

Giusy Tiseo et al. Infect Dis Ther. 2023 Jan.

Abstract

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.

Keywords: COVID-19; Molnupiravir; Nirmatrelvir/ritonavir; Progression; Remdesivir; SARS-CoV-2.

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Figures

Fig. 1
Fig. 1
Multivariable hazard ratios for factors associated with increased probability to have a negative nasopharyngeal swab within 10 days from the first positive one in patients treated with nirmatrelvir/ritonavir versus those treated with remdesivir. The multivariable model was adjusted for age < 80 years, adequate COVID-19 vaccination, ≥ two comorbidities, hypertension, time from symptom onset, hematological malignancy, immunosuppression, and chronic lung disease. Antiviral treatments were modeled as a time-dependent variable
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