Coronavirus Disease 2019 Outcomes Among Recipients of Anti‐CD20 Monoclonal Antibodies for Immune‐Mediated Diseases: A Comparative Cohort Study

  1. Naomi J. Patel
  2. Kristin M. D'Silva
  3. Tiffany Y‐T. Hsu
  4. Michael DiIorio
  5. Xiaoqing Fu
  6. Claire Cook
  7. Lauren Prisco
  8. Lily Martin
  9. Kathleen M. M. Vanni
  10. Alessandra Zaccardelli
  11. Yuqing Zhang
  12. Jeffrey A. Sparks
  13. Zachary S. Wallace

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Patients with immune‐mediated diseases treated with anti‐CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID‐19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown.

Methods

We identified patients with immune‐mediated diseases who received anti‐CD20 monoclonal antibodies within 1 year prior to the index date of polymerase chain reaction–confirmed COVID‐19 between January 31, 2020, and January 31, 2021. General population comparators with COVID‐19 were matched up 5:1 by age, sex, and polymerase chain reaction date. Unadjusted and multivariable adjusted (for age, race, body mass index, and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in recipients of anti‐CD20 monoclonal antibodies versus comparators were estimated by using Cox regression.

Results

We identified 114 cases patients COVID‐19 who had received anti‐CD20 monoclonal antibodies for immune‐mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID‐19 (mean age 54 years, 70% female). Patients treated with anti‐CD20 monoclonal antibodies had higher mortality (adjusted HR 2.16; 95% CI: 1.03‐4.54) than matched comparators. Risks of hospitalization (adjusted HR 0.88; 95% CI: 0.62‐1.26) and mechanical ventilation use (adjusted HR 0.82; 95% CI: 0.36‐1.87) were similar. Similar trends were seen in analyses according to type of indication (eg, rheumatic or neurologic disease) and duration of anti‐CD20 monoclonal antibody use (<1 or ≥1 year) and after patients with interstitial lung disease, those with cancer, and those on glucocorticoids prior to COVID‐19 diagnosis were excluded.

Conclusion

Patients who received anti‐CD20 monoclonal antibodies for immune‐mediated diseases prior to COVID‐19 had higher mortality following COVID‐19 than matched comparators, highlighting the urgent need to mitigate excess risks in recipients of anti‐CD20 monoclonal antibodies during the ongoing pandemic.

Article activity feed

  1. Version published to 10.1002/acr2.11386
  2. ScreenIT

    SciScore for 10.1101/2021.08.05.21261643: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the MGB Institutional Review Board (2020P000833).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The level of significance was set as a two-tailed p<0.05, and statistical analyses were completed using SAS statistical software (version 9.4; SAS Institute, Inc.).
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)
    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:
    Despite these strengths, our study has certain limitations. First, though our findings persisted after adjustment for covariates, there may be residual confounding by CD20 inhibitor indication, concomitant glucocorticoid use, or disease severity, as CD20 inhibitors are often used as initial induction therapy for severe immune-mediated diseases (e.g., ANCA-associated vasculitis) or as treatment for diseases that have been refractory to other therapies (e.g., rheumatoid arthritis). However, our findings remained robust in sensitivity analyses and subgroup analyses that addressed the potential impact of residual confounding. Regardless, one should cautiously interpret these results as applying to the population of patients with immune-mediated diseases treated with CD20 inhibitors in the context of the known effects of CD20 inhibitors on B cell responses and antibody production. Second, multivariable adjustment was limited in some subgroup and sensitivity analyses due to low event rates. However, the observed trends remained consistent with those observed in the primary analysis. In conclusion, we found an increased risk of death in patients with immune-mediated diseases who had received CD20 inhibitors prior to COVID-19 diagnosis. CD20 inhibitors are the standard of care for induction and maintenance treatment of multiple immune-mediated diseases, some of which have few alternatives. Additional studies are needed to evaluate the potential use of anti-SARS-CoV-2 monoclonal antib...

    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.

  3. Version published to 10.1101/2021.08.05.21261643v1 on medRxiv