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

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. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00729-2.

Real-World Study on Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Unvaccinated Patients with Chronic Respiratory Diseases with Confirmed SARS-CoV-2 Infection Managed in Out-Patient Setting

“…In a recent retrospective, observational, nationwide propensity-matched analysis comparing outcomes of US veterans 65 years and older with mild-to-moderate COVID-19, the composite primary outcome of admission or death within 30 days of diagnosis was reached less often in those receiving either MOV or NMV-r versus those that received no antiviral, while NMV-r was more effective than MOV in both outcomes [ 22 ]. The composite outcome of death or hospitalization was shown to be lower in NMV-r treated patients than MOV treated subjects in another study, but the difference in the degree of underlying co-morbidity could contribute to the difference [ 23 ]. Viral rebound was also shown to be uncommon for patients treated with both NMV-r and MOV [ 24 ].…”

“…Most of the published literature on the efficacy of NMV-r and MOV has focused on the whole population [ 5 , 6 , 21 ]. There have also been studies on selected patient subgroups including all COVID-19 subjects at high risk of progression [ 23 ], elderly populations [ 22 , 25 ], hematology patients [ 26 ] and solid organ transplant recipients [ 27 ]. However, there has not been any dedicated study focusing on patients with chronic respiratory disease, who are prone to developing severe COVID-19.…”

Molnupiravir: A Versatile Prodrug against SARS-CoV-2 Variants

“…A study by Tiseo et al suggested that the occurrence of death corresponding to COVID-19 was higher with remdesivir than with molnupiravir or nirmatrelvir/ritonavir [ 87 ]. Molnupiravir was found to be well tolerated when COVID-19 treatment was carried out on older patients and those with vaccination and comorbidities [ 88 ].…”

HIV and COVID-19 Co-Infection: Epidemiology, Clinical Characteristics, and Treatment

“…A single-center Italian study from Pisa found no significant difference in effectiveness when comparing molnupiravir (98.2%) to nirmatrelvir/ritonavir (99.2%) or 3-day remdesivir (94.9%), although nirmatrelvir/ritonavir proved more efficient at preventing the need for hospitalization when compared to remdesivir [ 107 ].…”