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

Abstract

While molnupiravir (MOV) and nirmatrelvir–ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. A territory-wide retrospective cohort study was conducted in Hong Kong to investigate the efficacy of MOV and NMV-r against severe outcomes of COVID-19 in unvaccinated adult patients with chronic respiratory diseases. A total of 3267 patients were included. NMV-r was effective in preventing respiratory failure (66.6%; 95% CI, 25.6–85.0%, p = 0.007), severe respiratory failure (77.0%; 95% CI, 6.9–94.3%, p = 0.039) with statistical significance, and COVID-19 related hospitalization (43.9%; 95% CI, −1.7–69.0%, p = 0.057) and in-hospital mortality (62.7%; 95% CI, −0.6–86.2, p = 0.051) with borderline statistical significance. MOV was effective in preventing COVID-19 related severe respiratory failure (48.2%; 95% CI 0.5–73.0, p = 0.048) and in-hospital mortality (58.3%; 95% CI 22.9–77.4, p = 0.005) but not hospitalization (p = 0.16) and respiratory failure (p = 0.10). In summary, both NMV-r and MOV are effective for reducing severe outcomes in unvaccinated COVID-19 patients with chronic respiratory diseases.

Effectiveness of nirmatrelvir‐ritonavir on severe outcomes of COVID‐19 in the era of vaccination and Omicron: An updated meta‐analysis

“…The large differences in underlying study populations, outcome definitions and inclusion criteria can probably explain at least part of this heterogeneity. Some studies focused on specific patient groups such as patients with inflammatory bowel disease, 41 solid organ transplant patients, 42 patients with chronic respiratory disease, 44 systemic rheumatic disease, 55 diabetes, 47 hematological malignancy, 56,59 and long-term facility residents. 48,50 Inclusion and exclusion criteria were not uniform across studies, and neither were outcome definitions, especially for the outcome of "disease progression.…”

Clinical effectiveness of nirmatrelvir plus ritonavir in patients with COVID‐19 and substance use disorders based on real‐world data

“…17,18 Studies have shown that compared with molnupiravir, NMV-r may provide a greater clinical benefit by decreasing the likelihood of hospitalization or mortality. [19][20][21] In the EPIC-HR trial, NMV-r significantly reduced hospitalization and mortality rates in nonhospitalized patients with mild-to-moderate COVID-19 who were at a risk of severe disease. The drug was effective when initiated within 3 or 5 days of symptom onset, with reductions of 89% or 88%, respectively.…”

“…Currently, two orally administered antiviral agents are available for nonhospitalized patients with COVID‐19 and those who are at high risk: a combination of nirmatrelvir and ritonavir (NMV‐r) and molnupiravir 17,18 . Studies have shown that compared with molnupiravir, NMV‐r may provide a greater clinical benefit by decreasing the likelihood of hospitalization or mortality 19–21 . In the EPIC‐HR trial, NMV‐r significantly reduced hospitalization and mortality rates in nonhospitalized patients with mild‐to‐moderate COVID‐19 who were at a risk of severe disease.…”

Nirmatrelvir/ritonavir for the treatment of immunocompromised adult patients with early‐stage symptomatic COVID‐19: A real‐life experience

“…9 In view of this evidence, the Food and Drug Administration and the European Medicines Agency issued in December 2021 and January 2022, respectively, the emergency use authorization (EUA) for NMV/r to treat mild-to-moderate laboratoryconfirmed COVID-19 in nonhospitalized patients at high risk of clinical progression, which include those who are immunocompromised. 10 In spite of the encouraging results from the EPIC-HR trial and the growing number of real-life studies performed in the general population, [11][12][13][14] the need of co-administration with ritonavir (a potent inhibitor of cytochrome CYP3A4) raises concerns about the potential for drug-to-drug interactions (DDIs) and associated adverse effects. 15 This circumstance has limited the use of NMV/r among patients receiving immunosuppressive therapies, thus narrowing their already limited options.…”

“…In spite of the encouraging results from the EPIC‐HR trial and the growing number of real‐life studies performed in the general population, 11–14 the need of co‐administration with ritonavir (a potent inhibitor of cytochrome CYP3A4) raises concerns about the potential for drug‐to‐drug interactions (DDIs) and associated adverse effects 15 . This circumstance has limited the use of NMV/r among patients receiving immunosuppressive therapies, thus narrowing their already limited options 16 .…”