Immune Response Following COVID-19 Vaccination (mRNA or Non-mRNA) in Patients with Relapsing Multiple Sclerosis Treated with the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib: An Update
Amit Bar-Or 1, Anne H. Cross2, Anthony Cunningham3, Yann Hyvert4, Andrea Seitzinger4, Elise E. Drouin5, Nektaria Alexandri4, Davorka Tomic6, Xavier Montalban7
1Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 2Washington University School of Medicine, 3Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 4The healthcare business of Merck KGaA, Darmstadt, Germany, 5EMD Serono, 6Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany, 7Department of Neurology-Neuroimmunology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d’Hebron
Objective:
To examine the humoral response to mRNA and non-mRNA COVID-19 vaccination in patients with relapsing multiple sclerosis (PwRMS) receiving evobrutinib during the open-label extension (OLE) of a Phase II trial (NCT02975349).
Background:
Evobrutinib is a highly selective, central nervous system-penetrant, covalent Bruton’s tyrosine kinase inhibitor being investigated in RMS. A preliminary analysis showed that evobrutinib-treated PwRMS (n=24) could mount an antibody response to mRNA COVID-19 vaccines.
Design/Methods:
Post hoc analysis of PwRMS who received both evobrutinib 75mg twice-daily (fasted) and COVID-19 vaccines during the OLE (n=45; mRNA n=37, non-mRNA n=8; booster n=14). Immunoglobulin G (IgG) anti-S1/S2 (SARS-CoV-2 spike protein domains) specific COVID-19-antibodies were measured using an indirect chemiluminescence immunoassay (DiaSorin Molecular LLC, USA; lower limit of quantification, 3.8 AU/mL; seronegative <15.0 AU/mL, seropositive ≥15 AU/mL).
Results:
Baseline mean (SD) age of patients was 46.0 (9.6) years, 68.9% were female and mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. Of 45 evobrutinib-treated patients, 43 developed or increased S1/S2 IgG antibody levels post-vaccination (geometric mean [SD] pre-/post-vaccination: mRNA 8.5 [4.3]/247.7 [4.5] AU/mL, non-mRNA 12.1 [3.2]/197.1 [6.2]). Patients who were either S1/S2 IgG seronegative (n=32) or seropositive (n=13) pre-vaccination demonstrated an antibody response following vaccination (seronegative pre-/post-vaccination geometric mean [SD]: 4.3 [1.3]/133.6 [3.7] AU/mL; seropositive pre-/post-vaccination: 55.5 [4.0]/984.4 [2.9]). Most patients (n=36/45), whether seronegative or positive, demonstrated a 10–100-fold increase of S1/S2 IgG antibody levels from pre- to post-vaccination (geometric mean [SD] fold change of S1/S2 IgG antibody levels for total/seronegative/seropositive patients: 26.4 [3.4]/31.0 [3.4]/17.7 [3.3]). S1/S2 IgG levels post-booster were higher versus post-vaccination.
Conclusions:
Prior data that evobrutinib-treated PwRMS mounted an antibody response to mRNA COVID-19 vaccination are supported further by this larger population analysis. These results provide additional evidence that evobrutinib-treated PwRMS can mount a humoral response to COVID-19 vaccinations and that, with boosters, antibody levels increase further than after the first vaccination cycle.