Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton’s tyrosine kinase inhibitor

Amit Bar-Or, Anne H. Cross, Anthony L. Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Gühring, Elise E. Drouin, Nektaria Alexandri, Davorka Tomic, Xavier Montalban

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton’s tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS). Objective: To investigate the effect of evobrutinib on immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinated patients with RMS from a Phase II trial (NCT02975349). Methods: A post hoc analysis of patients with RMS who received evobrutinib 75 mg twice daily and SARS-CoV-2 vaccines during the open-label extension (n = 45) was conducted. Immunoglobulin (Ig)G anti-S1/S2-specific SARS-CoV-2 antibodies were measured using an indirect chemiluminescence immunoassay. Results: In the vaccinated subgroup, mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. In total, 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination; one patient’s antibody response remained negative post-vaccination and the other had antibody levels above the upper limit of detection, both pre- and post-vaccination. Most patients (n = 36/45), regardless of pre-vaccination serostatus, had a 10–100-fold increase of antibody levels pre- to post-vaccination. Antibody levels post-booster were higher versus post-vaccination. Conclusion: These results suggest evobrutinib, an investigational drug with therapeutic potential for patients with RMS, acts as an immunomodulator, that is, it inhibits aberrant immune cell responses in patients with RMS, while responsiveness to foreign de novo and recall antigens is maintained.

Original languageEnglish
Pages (from-to)1471-1481
Number of pages11
JournalMultiple Sclerosis Journal
Volume29
Issue number11-12
DOIs
StatePublished - Oct 2023

Keywords

  • Bruton’s tyrosine kinase
  • COVID-19
  • Evobrutinib
  • SARS-CoV-2
  • multiple sclerosis
  • vaccines

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