Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk patients with COVID-19 in North West London: a retrospective cohort study using the Discover dataset

Drysdale et al., medRxiv, doi:10.1101/2023.07.26.23293188

Jul 2023

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Retrospective 599 high-risk sotrovimab patients and 5,191 untreated controls, showing lower hospitalization/mortality with treatment, without statistical significance in the overall cohort. Efficacy was better for those ≥65, and efficacy was lower in later time periods.

Confounding by treatment propensity. This study analyzes a population where only a fraction of eligible patients received the treatment. Patients receiving treatment may be more likely to follow other recommendations, more likely to receive additional care, and more likely to receive additional treatments that are not tracked in the data (e.g., nasal/oral hygiene c19early.org, c19early.org (B), vitamin D c19early.org (C), etc.) — either because the physician recommending sotrovimab also recommended them, or because the patient seeking out sotrovimab is more likely to be familiar with the efficacy of additional treatments. Therefore, these kind of studies may overestimate the efficacy of treatments.

Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.1 Liu, Sheward, VanBlargan and a lack of efficacy for BA.2 Zhou. US EUA has been revoked.

1. c19early.org, c19early.org/p.c19early.org/p.

2. c19early.org (B), c19early.org/ph.c19early.org/ph.

3. c19early.org (C), c19early.org/d.c19early.org/d.

4. Liu et al., Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2, bioRxiv, doi:10.1101/2021.12.14.472719.biorxiv.org, doi.org.

5. Sheward et al., Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron), bioRxiv, doi:10.1101/2021.12.19.473354.biorxiv.org, doi.org.

6. VanBlargan et al., An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies, bioRxiv, doi:10.1101/2021.12.15.472828.biorxiv.org, doi.org.

7. Zhou et al., SARS-CoV-2 Omicron BA.2 Variant Evades Neutralization by Therapeutic Monoclonal Antibodies, bioRxiv, doi:10.1101/2022.02.15.480166.biorxiv.org, doi.org.

Important missing comments or errors? Let us know.

risk of death, 29.0% lower, HR 0.71, p = 0.65, treatment 599, control 5,191, propensity score weighting, Cox proportional hazards.

risk of death, 45.0% lower, HR 0.55, p = 0.55, ≥65 years old, propensity score weighting, Cox proportional hazards.

risk of death, 98.0% higher, HR 1.98, p = 0.55, <65 years old, propensity score weighting, Cox proportional hazards.

risk of death, 41.0% lower, HR 0.59, p = 0.62, period 2, propensity score weighting, Cox proportional hazards.

risk of death, 4.0% higher, HR 1.04, p = 0.97, period 3, propensity score weighting, Cox proportional hazards.

risk of death/hospitalization, 50.0% lower, HR 0.50, p = 0.07, treatment 599, control 5,191, propensity score weighting, Cox proportional hazards.

risk of hospitalization, 57.0% lower, HR 0.43, p = 0.05, treatment 599, control 5,191, propensity score weighting, Cox proportional hazards.

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

Drysdale et al., 27 Jul 2023, retrospective, United Kingdom, preprint, 14 authors, study period August 2020 - March 2021.

Contact: myriam.g.drysdale@gsk.com.

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Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk patients with COVID-19 in North West London: a retrospective cohort study using the Discover dataset

Myriam Drysdale, Evgeniy R Galimov, Marcus J Yarwood, Vishal Patel, Bethany Levick, Daniel C Gibbons, Jonathan D Watkins, Sophie Young, Benjamin F Pierce, Emily J Lloyd, William Kerr, Helen J Birch, Tahereh Kamalati, Stephen J Brett

doi:10.1101/2023.07.26.23293188

Introduction: There is uncertainty regarding how in vitro antibody neutralisation activity translates to the clinical efficacy of sotrovimab against severe acute respiratory syndrome coronavirus 2, although real-world evidence has demonstrated continued effectiveness during both BA.2 and BA.5 predominance. We previously reported descriptive results from the Discover dataset for patients treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per National Health Service (NHS) criteria but who were untreated. This study sought to assess the effectiveness of sotrovimab compared with no early coronavirus disease 2019 (COVID-19) treatment in highest-risk patients with COVID-19. Methods: Retrospective cohort study using the Discover dataset in North West London. Patients had to be non-hospitalised at index, aged ≥12 years old and meet ≥1 of the NHS highest-risk criteria for receiving early COVID-19 treatment with sotrovimab. The primary objective was to assess the risk of COVID-19-related hospitalisation and/or COVID-19related death within 28 days of the observed/imputed treatment date between patients treated with sotrovimab and highest-risk patients who received no early COVID-19 treatment. We also performed subgroup analyses for patients aged <65 and ≥65 years, patients with renal dysfunction, and by Omicron subvariant prevalence period (BA.1/2

Authorship All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

References

Bottle, Cohen, Lucas, How an electronic health record became a realworld research resource: comparison between London's Whole Systems Integrated Care database and the Clinical Practice Research Datalink, BMC Med Inform Decis Mak

Cathcart, Havenar-Daughton, Lempp, The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2, bioRxiv

Cheng, Reyes, Satram, Real-world effectiveness of sotrovimab for the early treatment of COVID-19 during SARS-CoV-2 Delta and Omicron waves in the USA, Infect Dis Ther

Discover-Now, Our dataset: linked data

Drysdale, Gibbons, Singh, Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review, medRxiv

Gaudinski, Coates, Houser, Safety and pharmacokinetics of the Fcmodified HIV-1 human monoclonal antibody VRC01LS: a phase 1 open-label clinical trial in healthy adults, PLoS Med

Gov, UK. [internet]. Oral COVID-19 antiviral, Paxlovid, approved by UK regulator

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

Harman, Nash, Webster, Comparison of the risk of hospitalisation among BA.1 and BA.2 COVID-19 cases treated with sotrovimab in the community in England, medRxiv

Hippisley-Cox, Khunti, Sheikh, Nguyen-Van-Tam, Coupland, QCovid 4 -Predicting risk of death or hospitalisation from COVID-19 in adults testing positive for SARS-CoV-2 infection during the Omicron wave in England

Ko, Pegu, Rudicell, Enhanced neonatal Fc receptor function improves protection against primate SHIV infection, Nature

Mendiola-Pastrana, López-Ortiz, De La Loza-Zamora, González, Gómez-García et al., SARS-CoV-2 variants and clinical outcomes: a systematic review, Life (Basel)

Opensafely Collaborative, Linda, Effectiveness of sotrovimab and molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform, medRxiv

Park, Pinto, Walls, Imprinted antibody responses against SARS-CoV-2 Omicron sublineages, Science

Patel, Levick, Boult, Characteristics and outcomes of COVID-19 patients presumed to be treated with sotrovimab in NHS hospitals in England, medRxiv

Patel, Yarwood, Levick, Characteristics and outcomes of patients with COVID-19 at high-risk of disease progression receiving sotrovimab, oral antivirals or no treatment in England

Pinto, Park, Beltramello, Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody, Nature

Xu, Ross, Raebel, Shetterly, Blanchette et al., Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals, Value Health

Yinong, Gabrielle, Effectiveness of sotrovimab in preventing COVID-19-related hospitalizations or deaths among U.S. veterans

Zheng, Campbell, Carr, Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients on kidney replacement therapy: observational cohort study using the OpenSAFELY-UKRR linked platform and SRR database

Zheng, Green, Tazare, 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, BMJ

Zheng, Tazare, Nab, 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

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