Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies

  1. Irene Schiavetti
  2. Cinzia Cordioli
  3. Maria Laura Stromillo
  4. Maria Teresa Ferrò
  5. Alice Laroni
  6. Eleonora Cocco
  7. Gaia Cola
  8. Livia Pasquali
  9. Maria Teresa Rilla
  10. Elisabetta Signoriello
  11. Rosa Iodice
  12. Alessia Di Sapio
  13. Roberta Lanzillo
  14. Francesca Caleri
  15. Pietro Annovazzi
  16. Antonella Conte
  17. Giuseppe Liberatore
  18. Francesca Ruscica
  19. Renato Docimo
  20. Simona Bonavita
  21. Monica Ulivelli
  22. Paola Cavalla
  23. Francesco Patti
  24. Diana Ferraro
  25. Marinella Clerico
  26. Paolo Immovilli
  27. Massimiliano Di Filippo
  28. Marco Salvetti
  29. Maria Pia Sormani

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Abstract

Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines.

Objective:

In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs).

Methods:

Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT.

Results:

19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74–4.58, p < 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75–4.00, p < 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02).

Conclusions:

The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.

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  1. Version published to 10.1177/13524585221102918
  2. ScreenIT

    SciScore for 10.1101/2022.01.22.22269630: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: The study was approved by the regional ethics committee of Liguria (University of Genoa; n 130/2020–DB id 10433) and at a national level by the Italian Medicines Agency.
    IRB: The study was approved by the regional ethics committee of Liguria (University of Genoa; n 130/2020–DB id 10433) and at a national level by the Italian Medicines Agency.
    Consent: Written informed consent was obtained from all participants before starting any study procedures.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Each MS center was requested to report the number of pwMS vaccinated by two mRNA vaccine doses (BNT162b2 (Pfizer Inc, and BioNTech), or mRNA-1273 (Moderna Tx, Inc)) in each DMT group from March 2021 to December 25, 2021.
    BioNTech
    suggested: None

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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 10.1101/2022.01.22.22269630v1 on medRxiv