Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data

  1. Yinong Young-Xu
  2. Lauren Epstein
  3. Vincent C Marconi
  4. Victoria Davey
  5. Gabrielle Zwain
  6. Jeremy Smith
  7. Caroline Korves
  8. Fran Cunningham
  9. Robert Bonomo
  10. Adit A Ginde

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in this population, particularly after the emergence of the Omicron variant.

Objective

To determine the effectiveness of tixagevimab/cilgavimab for prevention of SARS-CoV-2 infection and severe disease among immunocompromised patients.

Design

Retrospective cohort study with propensity matching and difference-in-difference analyses.

Setting

U.S. Department of Veterans Affairs (VA) healthcare system.

Participants

Veterans age ≥18 years as of January 1, 2022, receiving VA healthcare. We compared a cohort of 1,848 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to matched controls selected from 251,756 patients who were on immunocompromised or otherwise at high risk for COVID-19. Patients were followed through April 30, 2022, or until death, whichever occurred earlier.

Main Outcomes

Composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used cox proportional hazards modelling to estimate the hazard ratios (HR) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes.

Results

Most (69%) tixagevimab/cilgavimab recipients were ≥65 years old, 92% were identified as immunocompromised in electronic data, and 73% had ≥3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to propensity-matched controls, tixagevimab/cilgavimab-treated patients had a lower incidence of the composite COVID-19 outcome (17/1733 [1.0%] vs 206/6354 [3.2%]; HR 0.31; 95%CI, 0.18-0.53), and individually SARS-CoV-2 infection (HR 0.34; 95%CI, 0.13-0.87), COVID-19 hospitalization (HR 0.13; 95%CI, 0.02-0.99), and all-cause mortality (HR 0.36; 95%CI, 0.18-0.73).

Limitations

Confounding by indication and immortal time bias.

Conclusions

Using national real-world data from predominantly vaccinated, immunocompromised Veterans, administration of tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection, COVID-19 hospitalization, and all-cause mortality during the Omicron surge.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2022.05.28.22275716: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: We analyzed electronic health records (EHR) using the VA Corporate Data Warehouse (CDW), which contains patient-level information on all patient encounters in VA medical facilities, including treatments, prescriptions, vaccinations, laboratory results, healthcare utilization, and vital status.9,10 We identified tixagevimab/cilgavimab use through the VA Pharmacy Benefits Management (PBM) EUA prescription dashboard, which captures and links records of recipients, date, and dosage of tixagevimab/cilgavimab administered in medical facilities across VA.11 This study was approved by the institutional review board of the VA Medical Center in White River Junction, Vermont, and was granted a waiver of informed consent because the study was deemed minimal risk and consent impractical to acquire.
    Consent: We analyzed electronic health records (EHR) using the VA Corporate Data Warehouse (CDW), which contains patient-level information on all patient encounters in VA medical facilities, including treatments, prescriptions, vaccinations, laboratory results, healthcare utilization, and vital status.9,10 We identified tixagevimab/cilgavimab use through the VA Pharmacy Benefits Management (PBM) EUA prescription dashboard, which captures and links records of recipients, date, and dosage of tixagevimab/cilgavimab administered in medical facilities across VA.11 This study was approved by the institutional review board of the VA Medical Center in White River Junction, Vermont, and was granted a waiver of informed consent because the study was deemed minimal risk and consent impractical to acquire.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Analyses were performed with Stata 17 software (StataCorp), and SAS software, version 8.2 (SAS Institute).
    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: There are some limitations to acknowledge. Firstly, VA data include only healthcare encounters occur in VA medical centers, so we could have missed some infections and hospitalizations that occurred outside VA, which could bias our results towards the null. Secondly, while the EUA criteria are intended for patients who are immunocompromised, a small proportion of patients (%) who received tixagevimab/cilgavimab were not immunocompromised based on our definition and it is possible that we misclassified these patients. Thirdly, the VA has a unique population (mostly male, older), and our results may not be generalizable to a larger population of patients that were not treated at the VA. 34 Fourthly, the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes from claims data have been shown to inadequately capture comorbidity and functional status.35 Because only 289 (17%) of patients in our propensity-score matched tixagevimab/cilgavimab cohort received a single dose of 150 mg/150 mg tixagevimab/cilgavimab, we did not have the sufficient sample size to compare the original dosage of 150mg/150mg to the revised dosage of 300mg/300mg to assess the optimal dosing of tixagevimab/cilgavimab in the current analysis. Finally, we could not assess optimal timing of tixagevimab/cilgavimab in relation to COVID-19 vaccine administration, nor could we identify a target population who would be optimal to receive tixage...

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.05.28.22275716v1 on medRxiv