Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform

Zheng et al., BMJ, doi:10.1136/bmj-2022-071932

Nov 2022

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Retrospective 3,331 sotrovimab and 2,689 molnupiravir patients in the UK, showing higher risk of combined hospitalization/death with molnupiravir.

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-10. Multiple analyses have identified variants potentially created by molnupiravir11-15.

Important missing comments or errors? Let us know.

Study covers sotrovimab and molnupiravir.

risk of death/hospitalization, 100% higher, HR 2.00, p = 0.005, treatment 61 of 2,689 (2.3%), control 34 of 3,331 (1.0%), adjusted per study, inverted to make HR<1 favor treatment, multivariable, Cox proportional hazards, day 60, model 4.

risk of death/hospitalization, 85.2% higher, HR 1.85, p = 0.01, treatment 55 of 2,689 (2.0%), control 32 of 3,331 (1.0%), adjusted per study, inverted to make HR<1 favor treatment, multivariable, Cox proportional hazards, day 28, model 4.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. Swanstrom et al., Lethal mutagenesis as an antiviral strategy, Science, doi:10.1126/science.abn0048.science.org, doi.org.

2. Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.mdpi.com, doi.org.

3. Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.wiley.com, doi.org.

4. Huntsman, M., An assessment of the reproductive toxicity of the anti-COVID-19 drug molnupiravir using stem cell-based embryo models, Master's Thesis, scholarspace.manoa.hawaii.edu/items/cd11342c-b4dc-44c0-8b44-ce6e3369c40b.hawaii.edu.

5. Zibat et al., N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody, iScience, doi:10.1016/j.isci.2023.107786.sciencedirect.com, doi.org.

6. Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.sciencedirect.com, doi.org.

7. Gruber et al., Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study, Journal of Medical Virology, doi:10.1002/jmv.29642.wiley.com, doi.org.

8. Marikawa et al., An active metabolite of the anti-COVID-19 drug molnupiravir impairs mouse preimplantation embryos at clinically relevant concentrations, Reproductive Toxicology, doi:10.1016/j.reprotox.2023.108475.sciencedirect.com, doi.org.

9. Zhou et al., β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247.oup.com, doi.org.

10. Chamod et al., Molnupiravir Metabolite--N4-hydroxycytidine Causes Cytotoxicity and DNA Damage in Mammalian Cells in vitro: N4-hydroxycytidine Induced Cytotoxicity DNA Damage, Asian Medical Journal and Alternative Medicine, 23:3, asianmedjam.com/index.php/amjam/article/view/1448.asianmedjam.com.

11. Focosi et al., The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country, Intervirology, doi:10.1159/000540282.karger.com, doi.org.

12. Sanderson et al., A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes, Nature, doi:10.1038/s41586-023-06649-6.nature.com, doi.org.

13. Fountain-Jones et al., Effect of molnupiravir on SARS-CoV-2 evolution in immunocompromised patients: a retrospective observational study, The Lancet Microbe, doi:10.1016/S2666-5247(23)00393-2.sciencedirect.com, doi.org.

14. Kosakovsky Pond et al., Anti-COVID drug accelerates viral evolution, Nature, doi:10.1038/d41586-023-03248-3.nature.com, doi.org.

15. twitter.com, twitter.com/LongDesertTrain/status/1597353291868155906.twitter.com/LongDesertTrain/status/1597353291868155906.

Zheng et al., 16 Nov 2022, retrospective, United Kingdom, peer-reviewed, mean age 52.0, 33 authors, study period 16 December, 2021 - 10 February, 2022, this trial compares with another treatment - results may be better when compared to placebo. Contact: laurie.tomlinson@lshtm.ac.uk.

This Paper Molnupiravir All

Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform

Bang Zheng, Amelia C A Green, John Tazare, Helen J Curtis, Louis Fisher, Linda Nab, Anna Schultze, Viyaasan Mahalingasivam, Edward P K Parker, William J Hulme, Sebastian C J Bacon, Nicholas J Devito, Christopher Bates, David Evans, Peter Inglesby, Henry Drysdale, Simon Davy, Jonathan Cockburn, Caroline E Morton, George Hickman, Tom Ward, Rebecca M Smith, John Parry, Frank Hester, Sam Harper, Amir Mehrkar, Rosalind M Eggo, Alex J Walker, Stephen J W Evans, Ian J Douglas, Brian Mackenna, Ben Goldacre, Laurie A Tomlinson

BMJ, doi:10.1136/bmj-2022-071932

Objective To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19. Design Observational cohort study with the OpenSAFELY platform. setting With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and 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 SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings. ParticiPants Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021. interventiOns Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units. Main OutcOMe Measures Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment. results Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were

References

Agarwal, Rochwerg, Lamontagne, A living WHO guideline on drugs for covid-19, BMJ, doi:10.1136/bmj.m3379

Austin, An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies, Multivariate Behav Res, doi:10.1080/00273171.2011.568786

Bager, Wohlfahrt, Bhatt, study group. Risk of hospitalisation associated with infection with SARS-CoV-2 omicron variant versus delta variant in Denmark: an observational cohort study, Lancet Infect Dis, doi:10.1016/S1473-3099(22)00154-2

Bernal, Da Silva, Musungaie, Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med, doi:10.1056/NEJMoa2116044

Brophy, Molnupiravir's authorisation was premature, BMJ, doi:10.1136/bmj.o443

Bruel, Hadjadj, Maes, Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies, Nat Med, doi:10.1038/s41591-022-01792-5

Cameroni, Bowen, Rosen, Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift, Nature, doi:10.1038/s41586-021-04386-2

Dal-Ré, Becker, Bottieau, Holm, Availability of oral antivirals against SARS-CoV-2 infection and the requirement for an ethical prescribing approach, Lancet Infect Dis, doi:10.1016/S1473-3099(22)00119-0

Grange, Buelo, Sullivan, Characteristics and risk of COVID-19-related death in fully vaccinated people in Scotland, Lancet, doi:10.1016/S0140-6736(21)02316-3

Grint, Wing, Gibbs, Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta, medRxiv, doi:10.1101/2022.05.03.22274602

Gupta, Gonzalez-Rojas, Juarez, Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab, N Engl J Med, doi:10.1056/NEJMoa2107934

Gupta, Gonzalez-Rojas, Juarez, Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial, JAMA, doi:10.1001/jama.2022.2832

Hoffmann, Krüger, Schulz, The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic, Cell, doi:10.1016/j.cell.2021.12.032

Iketani, Liu, Guo, Antibody evasion properties of SARS-CoV-2 Omicron sublineages, Nature, doi:10.1038/s41586-022-04594-4

Jo, Kim, Radnaabaatar, Model-based cost-effectiveness analysis of oral antivirals against SARS-CoV-2 in Korea, Epidemiol Health, doi:10.4178/epih.e2022034

Nhs, Neutralising monoclonal antibodies (nMABs) or antivirals for non-hospitalised patients with COVID-19

Nyberg, Ferguson, Nash, Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron, Lancet, doi:10.1016/S0140-6736(22)00462-7

Tada, Zhou, Dcosta, Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies, EBioMedicine, doi:10.1016/j.ebiom.2022.103944

Takashita, Yamayoshi, Simon, Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants, N Engl J Med, doi:10.1056/NEJMc2207519

Taylor, Adams, Hufford, De La Torre, Winthrop et al., Neutralizing monoclonal antibodies for treatment of COVID-19, Nat Rev Immunol, doi:10.1038/s41577-021-00542-x

Uraki, Kiso, Iida, Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2, Nature, doi:10.1038/s41586-022-04856-1

Vangeel, Chiu, Jonghe, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern, Antiviral Res, doi:10.1016/j.antiviral.2022.105252

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The primary care data were securely linked with data on SARS-CoV-2 infection ' 'and treatments, hospital admission, and death, over a period when both drug treatments were ' 'frequently prescribed in community settings.\n' ' \n' ' \n' ' Participants\n' ' Adult patients with covid-19 in the community at high risk of severe ' 'outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December ' '2021.\n' ' \n' ' \n' ' Interventions\n' ' Sotrovimab or molnupiravir given in the community by covid-19 medicine ' 'delivery units.\n' ' \n' ' \n' ' Main outcome measures\n' ' Admission to hospital with covid-19 (ie, with covid-19 as the primary ' 'diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause ' 'of death) within 28 days of the start of treatment.\n' ' \n' ' \n' ' Results\n' ' Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients ' 'were treated with sotrovimab and molnupiravir, respectively, with no substantial differences ' 'in baseline characteristics. 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