Early molnupiravir and nirmatrelvir-ritonavir show substantial clinical benefits in local hospitalized COVID-19 patients

In a local retrospective cohort study analyzing data during Hong Kong’s omicron BA.2 wave, molnupiravir and nirmatrelvir-ritonavir were found to be effective in reducing the risks of all-cause mortality and disease progression, as well as the need for oxygen therapy among hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without supplemental oxygen requirement.1 The study revealed the substantial clinical benefits of oral antivirals, supporting their early use among Coronavirus disease 2019 (COVID-19) patients in Hong Kong.1

Currently, molnupiravir and nirmatrelvir-ritonavir are 2 treatment options that have gained approval by the United States (US) Food and Drug Administration (FDA) for the treatment of patients with symptomatic COVID-19 and at high risk for progression to severe disease.2,3 In the MOVe-OUT trial, early treatment with molnupiravir was associated with a 31% lower risk of hospitalization or death vs. placebo among non-hospitalized patients (HR=0.69; 95% CI: 0.48-1.01).4 In the EPIC-HR trial, the combination of nirmatrelvir-ritonavir also showed a high efficacy of 89% relative risk reduction of progression to severe COVID-19 vs. placebo among non-hospitalized patients (p<0.001).5 Despite the positive trial results, real-world evidence is needed to reveal their effectiveness in a real-life local clinical setting amid the omicron-predominant period.1

A retrospective study was then performed to evaluate the efficacy of the oral antivirals molnupiravir and nirmatrelvir-ritonavir among hospitalized COVID-19 patients during the omicron BA.2 outbreak in Hong Kong.1 The study identified 40,776 adult patients hospitalized during the study period, comprising a total of 1,856 molnupiravir recipients and 890 nirmatrelvir-ritonavir recipients with a 1:1 propensity-score matching.1

The study results showed that molnupiravir and nirmatrelvir-ritonavir significantly reduced the risk of all-cause mortality by 52% (HR=0.48; 95% CI: 0.40-0.59; p<0.0001) and by 66% (HR=0.34; 95% CI: 0.23-0.50; p<0.0001) when compared with matched controls, respectively.1 Molnupiravir and nirmatrelvir-ritonavir also lowered the risk of progression to severe disease by 40%(HR=0.60; 95% CI: 0.52-0.69; p<0.0001) and by 43% (HR=0.57; 95% CI: 0.45-0.72; p<0.0001) vs. matched controls, respectively.1 Moreover, the need for supplemental oxygen therapy was significantly lower for patients who had received the oral antivirals (p<0.05).1 The use of these oral antivirals was also associated with a significantly shorter time to achieve a low viral burden (molnupiravir, HR=1.38, 95% CI: 1.15-1.64, p=0.0005; nirmatrelvir-ritonavir, HR=1.38; 95% CI: 1.07-1.79; p=0.013).1

Overall, during the omicron BA.2 wave in Hong Kong, early treatment with the oral antivirals molnupiravir and nirmatrelvir-ritonavir demonstrated significant clinical benefits in local hospitalized COVID-19 patients who did not require oxygen therapy, in terms of all-cause mortality, disease progression, the need for oxygen therapy, and the time to achieve a low viral burden.1 These findings supported the use of oral antivirals in the local population.1

  1. Wong CKH, et al. Real-world effectiveness of early molnupiravir or nirmatrelvir-ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study. Lancet Infect Dis. 2022;10(1016): S1473-3099
  2. Bhimraj A, et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Accessed November 5, 2022
  3. Arribas JR, et al. Randomized trial of molnupiravir or placebo in patients hospitalized with Covid-19. NEJM Evid. 2022;1(2).
  4. Bernal AJ, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med. 2022;386(6): 509-520
  5. Hammond J, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022;386(15): 1397-1408
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