Dataset Information

Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study.

ABSTRACT:

Background

In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19).

Methods

This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023.

Results

Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27-3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71-5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22-0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15-0.91) reduced the occurrence of adverse events.

Conclusion

The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.

SUBMITTER: Park JJ

PROVIDER: S-EPMC10615643 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study.

Park Jin Ju JJ Kim Hyunji H Kim Yong Kyun YK Lee Seung Soon SS Jung Eunju E Lee Jin Seo JS Lee Jacob J

Journal of Korean medical science 20231030 42

<h4>Background</h4>In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19).<h4>Methods</h4>This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from A ...[more]

PMID: 37904658

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Project description:ObjectiveTo determine the effectiveness of nirmatrelvir/ritonavir and molnupiravir among vaccinated and unvaccinated non-hospitalized adults with COVID-19.MethodsObservational studies of nirmatrelvir/ritonavir or molnupiravir compared to no antiviral drug treatment for COVID-19 in non-hospitalized adults with data on vaccination status were included. We searched MEDLINE, EMBASE, Scopus, Web of Science, WHO COVID-19 Research Database and medRxiv for reports published between 1 January 2022 and 8 November 2023. The primary outcome was a composite of hospitalization or mortality up to 35 days after COVID-19 diagnosis. Risk of bias was assessed with ROBINS-I. Risk ratios (RR), hazard ratios (HR) and risk differences (RD) were separately estimated using random-effects models.ResultsWe included 30 cohort studies on adults treated with nirmatrelvir/ritonavir (n = 462 279) and molnupiravir (n = 48 008). Nirmatrelvir/ritonavir probably reduced the composite outcome (RR 0.62, 95%CI 0.55-0.70; I2 = 0%; moderate certainty) with no evidence of effect modification by vaccination status (RR Psubgroup = 0.47). In five studies, RD estimates against the composite outcome for nirmatrelvir/ritonavir were 1.21% (95%CI 0.57% to 1.84%) in vaccinated and 1.72% (95%CI 0.59% to 2.85%) in unvaccinated subgroups.Molnupiravir may slightly reduce the composite outcome (RR 0.75, 95%CI 0.67-0.85; I2 = 32%; low certainty). Evidence of effect modification by vaccination status was inconsistent among studies reporting different effect measures (RR Psubgroup = 0.78; HR Psubgroup = 0.08). In two studies, RD against the composite outcome for molnupiravir were -0.01% (95%CI -1.13% to 1.10%) in vaccinated and 1.73% (95%CI -2.08% to 5.53%) in unvaccinated subgroups.ConclusionsAmong cohort studies of non-hospitalized adults with COVID-19, nirmatrelvir/ritonavir is effective against the composite outcome of severe COVID-19 independent of vaccination status. Further research and a reassessment of molnupiravir use among vaccinated adults are warranted.RegistrationPROSPERO CRD42023429232.

Project description:BackgroundFew studies evaluated the effectiveness of COVID-19 antivirals specifically in the asthma population This study assessed short- and long-term effects of nirmatrelvir/ritonavir versus molnupiravir in asthma population.MethodsThis is a retrospective cohort study on adult asthma patients infected with COVID-19, using real-world data obtained from the health officials in Hong Kong. Key inclusion criteria were infection with COVID-19 between March 16, 2022, and Oct 30, 2023, age ≥ 18 years, previous asthma diagnosis, and prescription history of an asthma medication. Outcomes included acute and post-acute mortality, post-acute all-cause hospitalization, and cause-specific hospitalization.Results1,745 patients were eligible for this study, with a median follow-up time of 365 days (IQR: 335-365). Patients in the nirmatrelvir/ritonavir group had significantly lower risks of acute inpatient death (HR, 0·27 [95% CI, 0·12 to 0·59]; p = 0·0011), post-acute inpatient death (HR, 0·49 [95% CI, 0·28 to 0·85]; p = 0·011), all-cause hospitalization (HR, 0·72 [95% CI, 0·58 to 0·89]; p = 0·0020), and myocardial infarction (HR, 0·10 [95% CI, 0·01 to 0·92]; p = 0·042) than patients in the control group. The risk of all-cause hospitalization was significantly lower in the nirmatrelvir/ritonavir group compared to the molnupiravir group (HR, 0·65 [95% CI, 0·52 to 0·81]; p = 0·00012). Among patients who were prescribed medium-/ high-dose inhaled corticosteroids, the nirmatrelvir/ritonavir group had a lower hazard of asthma exacerbation than the molnupiravir group (HR, 0·58 [95% CI, 0·35 to 0·95]; p = 0.030).ConclusionCompared with molnupiravir, nirmatrelvir/ritonavir may offer more benefits in reducing the risk of post-acute sequelae of COVID-19 among asthma patients. In addition, the post-acute benefits of the antivirals were also demonstrated in patients with mild asthma, which have not been generally recommended in existing clinical management guidelines.

Project description:BackgroundWhether hospitalized patients benefit from COVID-19 oral antivirals is uncertain.ObjectiveTo examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak.DesignTarget trial emulation study.SettingElectronic health databases in Hong Kong.ParticipantsThe molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (n = 7119).InterventionInitiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir.MeasurementsEffectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days.ResultsThe use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people.LimitationThe outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist.ConclusionMolnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed.Primary funding sourceHealth and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.

Project description:ImportanceSome patients treated with nirmatrelvir-ritonavir have experienced rebound of COVID-19 infections and symptoms; however, data are scarce on whether viral rebound also occurs in patients with COVID-19 receiving or not receiving molnupiravir.ObjectiveTo examine the incidence of viral rebound in patients with COVID-19 who were treated with the oral antiviral agents nirmatrelvir-ritonavir and molnupiravir.Design, setting, and participantsThis cohort study identified 41 255 patients with COVID-19 who were hospitalized from January 1, 2022, to March 31, 2022, in Hong Kong and assessed 12 629 patients with serial cycle threshold (Ct) values measured. Patients were followed up until the occurrence of the clinical end point of interest, death, date of data retrieval (July 31, 2022), or up to 30 days of follow-up, whichever came first.ExposuresMolnupiravir or nirmatrelvir-ritonavir treatment.Main outcomes and measuresViral rebound, defined as a Ct value greater than 40 that decreased to 40 or less.ResultsOf 12 629 patients (mean [SD] age, 65.4 [20.9] years; 6624 [52.5%] male), 11 688 (92.5%) were oral antiviral nonusers, 746 (5.9%) were molnupiravir users, and 195 (1.5%) were nirmatrelvir-ritonavir users. Compared with nonusers, oral antiviral users were older, had more comorbidities, and had lower complete vaccination rates. The mean (SD) baseline Ct value was slightly higher in nirmatrelvir-ritonavir users (22.2 [6.0]) than nonusers (21.0 [5.4]) and molnupiravir users (20.9 [5.4]) (P = .04). Viral rebound occurred in 68 nonusers (0.6%), 2 nirmatrelvir-ritonavir users (1.0%), and 6 molnupiravir users (0.8%). Among 76 patients with viral rebound, 12 of 68 nonusers, 1 of 6 molnupiravir users, and neither of the nirmatrelvir-ritonavir users died of COVID-19.Conclusions and relevanceIn this cohort study, viral rebound was uncommon in patients taking molnupiravir or nirmatrelvir-ritonavir and was not associated with increased risk of mortality. Given these findings, novel oral antivirals should be considered as a treatment for more patients with COVID-19 in the early phase of the infection.

Dataset Information

Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study.

Background

Methods

Results

Conclusion

Publications

Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study.

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