Dataset Information

Molnupiravir and Nirmatrelvir/Ritonavir: Tolerability, Safety, and Adherence in a Retrospective Cohort Study.

ABSTRACT:

Background

Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) were recently approved for the early treatment of COVID-19, but real-life data on tolerability, safety, and adverse events (AEs) are still scarce.

Methods

We conducted a retrospective cohort study including all patients who were prescribed MOL and NIR at the Infectious Diseases Unit of Padua University Hospital, between January and May 2022. Demographic, clinical, and safety variables were recorded.

Results

We included 909 patients, 48.3% males and 95.2% vaccinated against SARS-CoV-2. The median age was 73 (IQR: 62-82) years. MOL and NIR were prescribed in 407 (44.8%) and 502 (55.2%) patients, respectively. Overall, 124/909 (13.6%) patients experienced any AEs following antivirals intake: 98/124 (79%) patients reporting adverse events presented grade 1 AEs, 23/124 (18.5%) grade 2 AEs and 3 (2.5%) grade 3 AEs. Treatment discontinuation was recorded in 4.8% of patients. AEs were significantly higher in women, in patients treated with NIR compared to MOL and in people who were not vaccinated.

Conclusions

In our real-life setting, AEs were higher than those reported by clinical trials, and were particularly associated with NIR use and with not being vaccinated. Further analyses are needed to better assess safety of oral antivirals and to define which patient's profile may benefit most from MOL and NIR.

SUBMITTER: Mazzitelli M

PROVIDER: S-EPMC9962206 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Molnupiravir and Nirmatrelvir/Ritonavir: Tolerability, Safety, and Adherence in a Retrospective Cohort Study.

Mazzitelli Maria M Mengato Daniele D Sasset Lolita L Ferrari Anna A Gardin Samuele S Scaglione Vincenzo V Bonadiman Nicola N Calandrino Lucrezia L Cavinato Silvia S Trivellato Sabrina S Venturini Francesca F Cattelan Anna Maria AM

Viruses 20230128 2

<h4>Background</h4>Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) were recently approved for the early treatment of COVID-19, but real-life data on tolerability, safety, and adverse events (AEs) are still scarce.<h4>Methods</h4>We conducted a retrospective cohort study including all patients who were prescribed MOL and NIR at the Infectious Diseases Unit of Padua University Hospital, between January and May 2022. Demographic, clinical, and safety variables were recorded.<h4>Results</h4>We i ...[more]

PMID: 36851598

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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: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.

Project description:ObjectiveTo compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.DesignRetrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.SettingA real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.ParticipantsAdult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.InterventionsMolnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.Main outcome measuresAll-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.Statistical analysisCox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.ResultsBetween 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.ConclusionsIn higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.

Project description:IntroductionAzvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China.MethodsThis retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (PNANC), time to first nucleic-acid negative conversion (TFNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes.ResultsThis study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56-3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78-3.60; P = 0.189), PNANC (HR 0.87; 95% CI 0.69-1.09; P = 0.220), length of stay (β - 0.82; 95% CI - 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer TFNANC (β 2.53; 95% CI 0.76-4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses.ConclusionAzvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes.

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.

Dataset Information

Molnupiravir and Nirmatrelvir/Ritonavir: Tolerability, Safety, and Adherence in a Retrospective Cohort Study.

Background

Methods

Results

Conclusions

Publications

Molnupiravir and Nirmatrelvir/Ritonavir: Tolerability, Safety, and Adherence in a Retrospective Cohort Study.

Similar Datasets

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