Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe COVID-19 outcomes in non-hospitalised patients: an observational cohort study using the OpenSAFELY platform

  1. Bang Zheng
  2. Amelia CA Green
  3. John Tazare
  4. Helen J Curtis
  5. Louis Fisher
  6. Linda Nab
  7. Anna Schultze
  8. Viyaasan Mahalingasivam
  9. Edward PK Parker
  10. William J Hulme
  11. Sebastian CJ Bacon
  12. Nicholas J DeVito
  13. Christopher Bates
  14. David Evans
  15. Peter Inglesby
  16. Henry Drysdale
  17. Simon Davy
  18. Jonathan Cockburn
  19. Caroline E Morton
  20. George Hickman
  21. Tom Ward
  22. Rebecca M Smith
  23. John Parry
  24. Frank Hester
  25. Sam Harper
  26. Amir Mehrkar
  27. Rosalind M Eggo
  28. Alex J Walker
  29. Stephen JW Evans
  30. Ian J Douglas
  31. Brian MacKenna
  32. Ben Goldacre
  33. Laurie A Tomlinson

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Abstract

Objective

To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) vs. molnupiravir (an antiviral) 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 medications were frequently prescribed in community settings.

Participants

Non-hospitalised adult COVID-19 patients at high risk of severe outcomes treated with sotrovimab or molnupiravir since December 16, 2021.

Interventions

Sotrovimab or molnupiravir administered in the community by COVID-19 Medicine Delivery Units.

Main outcome measure

COVID-19 related hospitalisation or COVID-19 related death within 28 days after treatment initiation.

Results

Between December 16, 2021 and February 10, 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, with no substantial differences in their baseline characteristics. The mean age of all 6020 patients was 52 (SD=16) years; 59% were female, 89% White and 88% had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 87 (1.4%) COVID-19 related hospitalisations/deaths were observed (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographics, 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, HR=0.54, 95% CI: 0.33 to 0.88; P=0.014). Consistent results were obtained from propensity score weighted Cox models (HR=0.50, 95% CI: 0.31 to 0.81; P=0.005) and when restricted to fully vaccinated people (HR=0.53, 95% CI: 0.31 to 0.90; P=0.019). No substantial effect modifications by other characteristics were detected (all P values for interaction>0.10). Findings were similar in an exploratory analysis of patients treated between February 16 and May 1, 2022 when the Omicron BA.2 variant was dominant in England.

Conclusion

In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, those who received sotrovimab were at lower risk of severe COVID-19 outcomes than those receiving molnupiravir.

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  1. Version published to 10.1101/2022.05.22.22275417v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2022.05.22.22275417: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Software and reproducibility: Data management was performed using Python, with analysis carried out using Stata 16.1.
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and weaknesses: The key strengths of this study are the scale, level of detail and completeness of the underlying primary care EHR data and the linkage to multiple COVID-19 relevant national databases within the OpenSAFELY-TPP platform. In addition, the concurrent national rollout of sotrovimab and molnupiravir under similar indications between December 16, 2021 and February 10, 2022 enables us to make direct head-to-head comparisons for their effectiveness. Several limitations of this study need to be considered. Since the Omicron BA.1 variant was the dominant variant during the treatment period (December 2021-February 2022) [13], it is likely that our results can mainly be applied to this variant [14,15]. Whether the beneficial effect of sotrovimab persists for other variant subtypes warrants further investigation [14-17]. For instance, the Omicron BA.2 sublineage was shown to exhibit marked resistance to sotrovimab in in vitro experiments [18,19], whereas an in vivo experiment found both molnupiravir and sotrovimab can restrict viral replication in the lungs of BA.2- infected hamsters [20]. In addition, the patients included in this study are assumed to be only those who met the eligibility criteria made by NHS England [3], thus limiting further generalisation of our findings to people not in a known high-risk group. The possibility of residual confounding or measurement error cannot be ruled out in this real-world observational study, in particular related to di...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.05.22.22275417v1 on medRxiv