Real-world effectiveness of casirivimab and imdevimab among patients diagnosed with COVID-19 in the ambulatory setting: a retrospective cohort study using a large claims database

  1. Mohamed Hussein
  2. Wenhui Wei
  3. Vera Mastey
  4. Robert J Sanchez
  5. Degang Wang
  6. Dana J Murdock
  7. Boaz Hirshberg
  8. David M Weinreich
  9. Jessica J Jalbert

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Abstract

To assess the real-world effectiveness of casirivimab and imdevimab (CAS+IMD) versus no COVID-19 antibody treatment among patients diagnosed with COVID-19 in the ambulatory setting, including patients diagnosed during the Delta-dominant period prior to Omicron emergence.

Design

Retrospective cohort study.

Setting

Komodo Health closed claims database.

Participants

13 273 128 patients diagnosed with COVID-19 (December 2020 through September 2021) were treated with CAS+IMD or untreated but treatment eligible under the Emergency Use Authorization (EUA). Each treated patient was exact and propensity score matched without replacement to up to five untreated EUA-eligible patients.

Interventions

CAS+IMD.

Primary and secondary outcome measures

Composite endpoint of 30-day all-cause mortality or COVID-19-related hospitalisation. Kaplan-Meier estimators were used to calculate outcome risks overall and across subgroups: age, COVID-19 vaccination status, immunocompromised status, and timing of diagnosis (December 2020 to June 2021, and July to September 2021). Cox proportional hazards models were used to estimate adjusted HRs (aHRs) and 95% CIs.

Results

Among 75 159 CAS+IMD-treated and 1 670 338 EUA-eligible untreated patients, 73 759 treated patients were matched to 310 688 untreated patients; matched patients were ~50 years, ~60% were women and generally well balanced across risk factors. The 30-day risk of the composite outcome was 2.1% and 5.2% in the CAS+IMD-treated and CAS+IMD-untreated patients, respectively; equivalent to a 60% lower risk (aHR 0.40; 95% CI, 0.38 to 0.42). The effect of CAS+IMD was consistent across subgroups, including those who received a COVID-19 vaccine (aHR 0.48, 95% CI, 0.41 to 0.56), and those diagnosed during the Delta-dominant period (aHR 0.40, 95% CI, 0.38 to 0.42).

Conclusions

The real-world effectiveness of CAS+IMD is consistent with the efficacy for reducing all-cause mortality or COVID-19-related hospitalisation reported in clinical trials. Effectiveness is maintained across patient subgroups, including those prone to breakthrough infections, and was effective against susceptible variants including Delta. 

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  1. Version published to 10.1136/bmjopen-2022-064953
  2. ScreenIT

    SciScore for 10.1101/2022.05.19.22272842: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Since all data are de-identified and fully compliant with HIPAA, institutional review board/ethics committee approval was not required for this study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The analytic file was created and all analyses were conducted using SAS software (version 9.4, SAS Institute Inc.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Limitations of this study include that information on viral load and symptoms, variables that may predict severe COVID-19,49-51 are not captured in claims data. Moreover, a reason that at least some EUA-eligible patients were untreated may be that they had less severe disease, although social and cultural factors have also been reported to play a role in the decision for treatment with mAbs.52 If untreated patients had less severe disease than treated patients, the residual confounding would likely bias results against CAS+IMD. Another limitation is that several important variables such as BMI and COVID-19 vaccination status are not well captured in claims data; when this study was conducted, approximately 70% of the population had received 1 dose and 60% had received 2 doses. Residual confounding is likely, and if unvaccinated patients with higher BMIs are likely to have worse disease requiring treatment, it could result in underestimation of the effectiveness of CAS+IMD. We were also not able to distinguish between the subcutaneous and intravenous administration of CAS+IMD. Finally, the study period did not overlap with emergence of the Omicron variant, although CAS+IMD is not expected to be active against Omicron,53 as in vitro data indicate CAS+IMD has markedly reduced neutralization activity against this variant.54,55

    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 10.1101/2022.05.19.22272842v1 on medRxiv