Dataset Information

Real-world Effectiveness of Molnupiravir and Nirmatrelvir/Ritonavir as Treatments for COVID-19 in Patients at High Risk.

ABSTRACT:

Background

Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable.

Methods

The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy.

Results

Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR, 0.31; P < .001) and death (OR, 0.28; P < .001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence.

Conclusions

Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations.

SUBMITTER: Paraskevis D

PROVIDER: S-EPMC10733724 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Real-world Effectiveness of Molnupiravir and Nirmatrelvir/Ritonavir as Treatments for COVID-19 in Patients at High Risk.

Paraskevis Dimitrios D Gkova Maria M Mellou Kassiani K Gerolymatos Gerasimos G Psalida Naya N Gkolfinopoulou Kassiani K Kostaki Evangelia-Georgia EG Loukides Stylianos S Kotanidou Anastasia A Skoutelis Athanasios A Thiraios Eleftherios E Saroglou Georgios G Zografopoulos Dimitrios D Filippou Dimitrios D Mossialos Elias E Zaoutis Theoklis T Gaga Mina M Tsiodras Sotirios S Antoniadou Anastasia A

The Journal of infectious diseases 20231201 12

<h4>Background</h4>Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable.<h4>Methods</h4>The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy.<h4>Results</h4>Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40 ...[more]

PMID: 37565522

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Project description:Background Nirmatrelvir-ritonavir is highly effective in preventing severe coronavirus disease 2019 (COVID-19) in high-risk patients with mild-to-moderate severity. However, real-world performance data are limited, and the drug is not so acceptable to the COVID-19 patients at high risk who need it in Korea. Methods To evaluate the effectiveness of nirmatrelvir-ritonavir, we conducted a propensity score-matched retrospective cohort study on patients with mild-to-moderate COVID-19 at high risk for a severe disease who were hospitalized at four hospitals in South Korea from February 2022 to April 2022. A total of 236 patients in the treatment group (administered nirmatrelvir-ritonavir) and 236 in the matched control group (supportive care only) were analyzed for the primary outcome, i.e., the time to oxygen support-free survival. The secondary outcome was a composite result of disease progression. The reason for not prescribing nirmatrelvir-ritonavir to the indicated patients was also investigated. Results The treatment group showed significantly longer oxygen support-free survival than the matched control group (adjusted hazard ratio [aHR], 0.07; 95% confidence interval [CI], 0.01–0.31; P < 0.001). Multivariate Cox regression analysis showed that age (aHR, 1.03; 95% CI, 1.00–1.07), National Early Warning Score-2 at admission (aHR, 1.36; 95% CI, 1.08–1.71), nirmatrelvir-ritonavir treatment, female sex (aHR, 0.37; 95% CI, 0.15–0.88), and time from symptom onset to admission (aHR, 0.67; 95% CI, 0.48–0.95) were significantly associated with oxygen therapy. However, none of the factors were related to the composite outcome. In the unmatched control group, 19.9% of 376 patients had documented explanations for nirmatrelvir-ritonavir non-prescription, and 44.0% of these were due to contraindication criteria. In the treatment group, 10.9% of patients discontinued the medication primarily because of adverse events (71.4%), with gastrointestinal symptoms being the most common (50.0%). Conclusion Nirmatrelvir-ritonavir treatment significantly reduced oxygen therapy requirements in high-risk patients with COVID-19 during the omicron variant surge in South Korea. Physicians are encouraged to consider the active use of nirmatrelvir-ritonavir and to be watchful for gastrointestinal symptoms during medication. Graphical Abstract

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: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:Background: Nirmatrelvir/ritonavir (NMV/r) and molnupiravir are oral antiviral drugs approved for the treatment of early symptomatic patients with mild to moderate COVID-19 at high risk of progression to severe disease in Japan. Objective: This study evaluated, from a Japanese payer perspective, the cost-effectiveness of NMV/r compared with molnupiravir among patients with COVID-19. Methods: This cost-effectiveness model describes the COVID-19 disease history and the impact of antiviral treatment on short-term and long-term outcomes. Nirmatrelvir/ritonavir was compared with molnupiravir, and in the scenario analysis NMV/r was compared with standard of care over a lifetime horizon. Results: When compared with molnupiravir, NMV/r showed higher quality-adjusted life years (QALYs) (15.752 vs 15.739) and higher total cost (¥6 248 014 vs ¥6 245 829 [US 44 136.86 v s 44 121.42]). The incremental cost-effectiveness ratio was ¥164 934 (US 1165.12 ) p e r Q A L Y g a i n e d , w h i c h w a s l o w e r t h a n t h e w i l l i n g n e s s - t o - p a y ( W T P ) t h r e s h o l d i n J a p a n ( ¥ 5 000 000 / Q A L Y [ U S 35 320.71/QALY]). In the scenario analysis, the incremental cost-effectiveness ratio was ¥3 646 821 (US 25 761.66 ) p e r Q A L Y g a i n e d . O n e - w a y s e n s i t i v i t y a n a l y s i s a n d p r o b a b i l i s t i c s e n s i t i v i t y a n a l y s i s s h o w e d t h a t N M V / r w a s c o s t - e f f e c t i v e c o m p a r e d w i t h m o l n u p i r a v i r a n d s t a n d a r d o f c a r e c o n s i s t e n t l y . A l l r e s u l t s o f o n e - w a y s e n s i t i v i t y a n a l y s i s s h o w e d t h a t t h e i n c r e m e n t a l c o s t - e f f e c t i v e n e s s r a t i o s w e r e b e l o w t h e W T P t h r e s h o l d i n J a p a n . T h e r e s u l t o f t h e c o s t - e f f e c t i v e n e s s a c c e p t a b i l i t y c u r v e s h o w e d t h a t t h e p r o b a b i l i t y t h a t t h e i n c r e m e n t a l c o s t - e f f e c t i v e n e s s r a t i o w a s b e l o w t h e W T P o f ¥ 5 000 000 / Q A L Y ( U S 35 320.71/QALY) was 100.00%. Conclusion: Nirmatrelvir/ritonavir is cost-effective compared with molnupiravir and standard of care from a Japanese payer perspective. This study provides evidence for the cost-effectiveness of NMV/r for patients with COVID-19.

Dataset Information

Real-world Effectiveness of Molnupiravir and Nirmatrelvir/Ritonavir as Treatments for COVID-19 in Patients at High Risk.

Background

Methods

Results

Conclusions

Publications

Real-world Effectiveness of Molnupiravir and Nirmatrelvir/Ritonavir as Treatments for COVID-19 in Patients at High Risk.

Similar Datasets

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