TY - JOUR
T1 - Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib
T2 - A Bruton's tyrosine kinase inhibitor
AU - Bar-Or, Amit
AU - Cross, Anne H
AU - Cunningham, Anthony L
AU - Hyvert, Yann
AU - Seitzinger, Andrea
AU - Gühring, Hans
AU - Drouin, Elise E
AU - Alexandri, Nektaria
AU - Tomic, Davorka
AU - Montalban, Xavier
N1 - Publisher Copyright:
© The Author(s), 2023.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - Bruton's tyrosine kinase
KW - Covid-19
KW - Evobrutinib
KW - Multiple sclerosis
KW - SARS-CoV-2
KW - Vaccines
UR - http://www.scopus.com/inward/record.url?scp=85169587511&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/3d80f977-e959-3d89-914a-dc5e6bf0c241/
U2 - 10.1177/13524585231192460
DO - 10.1177/13524585231192460
M3 - Article
C2 - 37626477
SN - 1352-4585
VL - 29
SP - 1471
EP - 1481
JO - Multiple sclerosis (Houndmills, Basingstoke, England)
JF - Multiple sclerosis (Houndmills, Basingstoke, England)
IS - 11-12
M1 - 13524585231192460
ER -