Expert Opinion on COVID-19 Vaccination and the Use of Cladribine Tablets in Clinical Practice

  1. Peter Rieckmann
  2. Diego Centonze
  3. Gavin Giovannoni
  4. Le H. Hua
  5. Celia Oreja-Guevara
  6. Daniel Selchen
  7. Per Soelberg Sørensen
  8. Patrick Vermersch
  9. Heinz Wiendl
  10. Hashem Salloukh
  11. Bassem Yamout

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Abstract

Background

Gaps in current evidence and guidance leave clinicians with unanswered questions on the use of cladribine tablets for the treatment of multiple sclerosis (MS) in the era of the COVID-19 pandemic, in particular relating to COVID-19 vaccination.

Objective

We describe a consensus-based program led by international MS experts with the aim of supplementing current guidelines and treatment labels by providing timely recommendations relating to COVID-19 vaccination and the use of cladribine tablets in clinical practice.

Methods

A steering committee (SC) of 10 international MS experts identified seven clinical questions to answer concerning the use of cladribine tablets and COVID-19 vaccination, which addressed issues relating to patient selection, timing and efficacy, and safety. Clinical recommendations to address each question were drafted using available evidence combined with expert opinion from the SC. An extended faculty of 28 MS experts, representing 19 countries, in addition to the 10 SC members, voted on the recommendations. Consensus on recommendations was achieved when ≥75% of respondents expressed an agreement score of 7–9, on a 9-point scale.

Results

Consensus was achieved on all 13 recommendations. Clinical recommendations are provided on whether all patients with MS receiving cladribine tablets should be vaccinated against COVID-19, and whether they should be prioritized; the timing of vaccination around dosing of cladribine tablets (i.e., before and after a treatment course); and the safety of COVID-19 vaccination for these patients.

Conclusions

These expert recommendations provide timely guidance on COVID-19 vaccination in patients receiving cladribine tablets, which is relevant to everyday clinical practice.

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  1. Version published to 10.1101/2021.06.22.21259308v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.06.22.21259308: (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

    No key resources detected.

    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:
    One of the weaknesses of the consensus was the limited availability of data, i.e., specific studies looking at SARS-CoV-2 antibody responses or COVID-19 vaccination in patients with MS. Large, controlled trials on vaccination are needed, particularly with respect to people with MS on DMTs. In the time since voting took place, new evidence has been published in these areas.49-51 The humoral response to the BNT162b2 COVID-19 vaccine was assessed in 125 people with MS; of these 23 were receiving treatment with cladribine tablets (median time from last treatment dose to vaccination was 7.1 months). All patients treated with cladribine tablets were efficiently vaccinated and developed a protective SARS-CoV-2 antibody titre, even with vaccination as early as 4.4 months after the last treatment dose.50 It is reassuring to see that people with MS receiving cladribine tablets mounted good immune responses to COVID-19 vaccination; however, it is important to note that the sample size in this study was small, and additional trials with a larger number of patients are needed. It should be noted that, at the time of writing, no data on the clinical effectiveness of the COVID-19 vaccines are available from people with MS whether treated with DMTs or not. The safety of the BNT162b2 COVID-19 vaccine was assessed in a cohort of adults with MS; 555 patients received the first dose and 435 received the second dose, of which 414 (74.6%) and 326 (74.9%), were being treated with immunomodulatory d...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT03364036Active, not recruitingEvaluation of the Onset of Action in Highly Active MS (MAGNI…
    NCT03963375RecruitingCladribine Tablets: Collaborative Study to Evaluate Impact O…

    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.

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  3. Version published to 10.1101/2021.06.22.21259308v1 on medRxiv
  4. Version published to 10.1177/17562864211058298