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0 0.5 1 1.5 2+ Death/hospitalization -285% Improvement Relative Risk c19early.org/m Zheng et al. Molnupiravir for COVID-19 EARLY TREATMENT Favors molnupiravir Favors paxlovid
Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform
Zheng et al., medRxiv, doi:10.1101/2023.01.20.23284849 (Preprint)
Zheng et al., Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19.., medRxiv, doi:10.1101/2023.01.20.23284849 (Preprint)
Jan 2023   Source   PDF  
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OpenSAFELY retrospective 5,638 outpatients in the UK, showing significantly higher hospitalization/death for molnupiravir compared with paxlovid.
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer [Hadj Hassine, Swanstrom]. See [twitter.com] for analysis of a variant potentially created by molnupiravir. This study is excluded in the after exclusion results of meta analysis: study compares against another treatment showing significant efficacy.
risk of death/hospitalization, 284.6% higher, HR 3.85, p = 0.004, treatment 11 of 802 (1.4%), control 33 of 4,836 (0.7%), inverted to make HR<1 favor treatment, COVID-19 related, propensity score weighting, Cox proportional hazards, day 28, model 4.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Zheng et al., 22 Jan 2023, retrospective, United Kingdom, preprint, 9 authors, study period 11 February, 2022 - 1 October, 2022, this trial compares with another treatment - results may be better when compared to placebo.
Contact: laurie.tomlinson@lshtm.ac.uk.
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Abstract: medRxiv preprint doi: https://doi.org/10.1101/2023.01.20.23284849; this version posted January 22, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in nonhospitalised patients: observational cohort study using the OpenSAFELY platform Bang Zheng1, John Tazare1, Linda Nab2, Amir Mehrkar2, Brian MacKenna2, Ben Goldacre2, Ian J Douglas1, Laurie A Tomlinson1, on behalf of The OpenSAFELY Collaborative 1 London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK 2 The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, UK Correspondence to: Laurie A Tomlinson; Email: laurie.tomlinson@lshtm.ac.uk 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2023.01.20.23284849; this version posted January 22, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Abstract Objective: To compare the effectiveness of Paxlovid vs. sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients. Design: With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Setting: Patient-level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death within the OpenSAFELY-TPP platform, covering a period where both Paxlovid and sotrovimab were first-line treatment options in community settings. Participants: Non-hospitalised adult COVID-19 patients at high risk of severe outcomes treated with Paxlovid, sotrovimab or molnupiravir between February 11, 2022 and October 1, 2022. Interventions: Paxlovid, sotrovimab or molnupiravir administered in the community by COVID19 Medicine Delivery Units. Main outcome measure: COVID-19 related hospitalisation or COVID-19 related death within 28 days after treatment initiation. Results: A total of 7683 eligible patients treated with Paxlovid (n=4836) and sotrovimab (n=2847) were included in the main analysis. The mean age was 54.3 (SD=14.9) years; 64% were female, 93% White and 93% had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 52 (0.68%) COVID-19 related hospitalisations/deaths were observed (33 (0.68%) treated with Paxlovid and 19 (0.67%) with sotrovimab). Cox proportional hazards model stratified by region showed that after adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, treatment with Paxlovid was associated with a similar risk of outcome event as treatment with sotrovimab (HR=1.14, 95% CI: 0.62 to 2.08; P=0.673). Results from propensity score weighted Cox model also showed comparable risks in these two..
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