Efficacy study of Paxlovid and Molnupiravir under real conditions shows positive results

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In a recently published study medRxiv* Pre-print servers, researchers evaluated the efficacy of oral antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), molnupiravir (Lagevrio), or nirmatrelvir/ritonavir (Paxlovid) in a real-world setting.

Few studies have evaluated oral antivirals for the Coronavirus Disease 2019 (COVID-19) virus in patients without supplemental oxygen. In the absence of supporting data, the medical community has prioritized the distribution of these drugs to those at highest risk of disease progression, e.g. B. under-vaccinated elderly with multiple pre-existing comorbidities.

To learn: Real-world efficacy of molnupiravir and nirmatrelvir/ritonavir in hospitalized COVID-19 patients during the Omicron BA.2 wave in Hong Kong: an observational study. Photo credit: NIAID

About the study

In the present observational study, researchers enrolled COVID-19 patients hospitalized in Hong Kong between February 26, 2022 and May 5, 2022. Study patients did not receive supplemental oxygen but received either molnupiravir or nirmatrelvir/ritonavir treatment.

They were either admitted to hospitals within three days of their COVID-19 diagnosis or had confirmed COVID-19 within three days of their admission. This helped researchers account for potential time delays in confirming COVID-19.

The date of hospital admission (Day 0) was the index date. The researchers also defined the duration of treatment as two days after hospital admission. The team followed patients from the index date until death or other outcome events, a switch in oral antiviral treatment, or the end of the study period.

The team selected study controls who were not receiving oral antiviral drugs but were hospitalized for COVID-19, with a propensity score ratio of 1:4. They compared the patients in the test and control groups for changes in their clinical status, including death in the hospital, introduction of supplemental oxygen, no oxygen supply, and discharge from the hospital.

Researchers also performed logistic regression of study baseline covariates such as gender, age, symptom onset, and Charlson Comorbidity Index (CCI) to estimate propensity to take each drug. Using the standardized mean difference (SMD), the team assessed the balance of each baseline covariate between the test and control groups before and after propensity score matching. The SMD greater than 0.1 indicated an imbalance of the covariates.

In addition, the team used the Cox regression model to estimate the hazard ratios (HRs) of event outcomes with 95% confidence intervals (CI) between oral antiviral users and controls. After re-matching the two study groups’ covariates to baseline, they further analyzed the efficacy of molnupiravir and nirmatrelvir/ritonavir on each endpoint.

Graphs of cumulative incidence of (a) composite progression score, (b) all-cause mortality, and (c) lower viral load for molnupiravir users compared to t-matched controls and (a) composite progression score, (b) all-cause mortality, and (c) lower viral load for nirmatrelvir/ritonavir users compared to their comparator controls

Graphs of cumulative incidence of (a) composite progression score, (b) all-cause mortality, and (c) lower viral load for molnupiravir users compared to t-matched controls and (a) composite progression score, (b) all-cause mortality, and (c) lower viral load for nirmatrelvir/ritonavir users compared to their comparator controls

study results

With a median follow-up of 41.3 days, 40,776 patients with confirmed COVID-19 were hospitalized between February and April 2022. Of these, 2,359 and 1,000 patients were prescribed molnupiravir and nirmatrelvir/ritonavir, respectively, during hospital admission. After a 1:4 propensity score matching, there were 2116 molnupiravir users with 8396 matched controls and 991 nirmatrelvir/ritonavir users with 3952 matched controls.

The proportion of patients who received molnupiravir 800 mg twice daily for five days was 96.2%, while the proportion of patients who completed five days of nirmatrelvir 300 mg with ritonavir 100 mg twice daily was 98.5%.

The all-cause mortality (crude) incidence rates for molnupiravir were 22.24 and 1.06 events per 10,000 person-days, respectively. Likewise, for nirmatrelvir/ritonavir users, the events were 11.04 and 1.75 per 10,000 person-days, respectively. In addition, molnupiravir users had a reduced risk of invasive mechanical ventilation (IMV) with a HR of 0.31, 95% CI. The time to reach a lower viral load was significantly shorter in patients prescribed antivirals than in matched controls. The HRs for the same were 1.21 in molnupiravir users and 1.25 in nirmatrelvir/ritonavir users.

In-hospital deaths were noticeably higher in the control group compared to antiviral users at day 3 from baseline. Accordingly, the proportion of subjects with in-hospital deaths was 1.4% vs 0.6% for molnupiravir users and 1.1% vs 0.4% for nirmatrelvir/ritonavir users compared to controls. A similar pattern persisted through day 28 of follow-up; the proportion of subjects with in-hospital deaths was 14.8% vs 8.3% for molnupiravir users and 10.3% vs 3.2% for nirmatrelvir/ritonavir users. After 1:1 propensity matching, the authors found a higher risk of mortality (HR=1.53) and longer length of hospital stay (0.83 days) in molnupiravir users.

Conclusions

Oral antiviral drugs, molnupiravir and nirmatrelvir/ritonavir reduced the risk of disease progression and all-cause mortality even against the omicron subvariant BA.2 in real-world conditions. In addition, they dropped viral loads faster than the corresponding controls. Treatment with molnupiravir also reduced the risk of initiating IMV; likewise, therapy with nirmatrelvir/ritonavir shortened the length of hospital stay.

A head-to-head comparison showed that nirmatrelvir/ritonavir treatment reduced the risk of death more than molnupiravir use. Overall, the study showed that these oral antivirals could treat people at higher risk of severe COVID-19. However, more research is needed to provide information on the safety and effectiveness of oral antiviral drugs in specific settings, populations, and healthcare settings.

*Important NOTE

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be relied upon as conclusive, guide clinical practice/health behavior, or be treated as established information.

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