Antibody Levels in Evobrutinib-Treated Relapsing Multiple Sclerosis Increased Following COVID-19 Vaccination

Amit Bar-Or, MD, FRCP, FAAN, FANA

New data from an open-label extension phase 2 trial (NCT02975349) showed that evobrutinib-treated patients with relapsing multiple sclerosis (RMS) had increased S1/S2 immunoglobuin (IgG) antibody levels after being given two doses of the mRNA COVID-19 vaccination.¹ This was the first evidence for any humoral response to vaccine administration for those on a Bruton’s tyrosine kinase inhibitor (BTKi).

After patients received 2 doses of mRNA vaccine, all but one of the 24-patient cohort treated with evobrutinib had an increased development of S1/S2 IgG antibody levels. Pre-vaccination, the geometric mean was 6.7 (standard deviation [SD], 2.6) AU/mL and increased to 209.1 (SD, 3.6) AU/mL post-vaccination. Meanwhile, the median pre- and post-vaccination S1/S2 IgG antibody levels were 3.8 and185.0 AU/mL, respectively.

Notably, patients who were either S1/S2 IgG seronegative or seropositive pre-vaccination had a strong antibody response following vaccination. Specifically, for seronegative patients, pre-vaccination as antibody levels were 3.8 AU/mL and increased to 167.0 AU/mL post-vaccination. For those who were seropositive, antibody levels increased from a median of 26.2 AU/mL to 715.0 AU/mL after vaccination.

The research was presented as a late breaker poster at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), October 26-28, in Amsterdam, Netherlands, by coauthor Amit Bar-Or, MD, FRCP, FAAN, FANA, Melissa and Paul Anderson professor of neurology, presidential endowed chair, Perelman School of Medicine, University of Pennsylvania, and colleagues.

Bar-Or et al noted, “An antibody response after receiving the mRNA vaccine was observed independently of whether patients were seronegative or seropositive prior to vaccination. This response was in the range observed for healthy controls and untreated MS patients receiving an mRNA vaccine. Seropositive versus seronegative patients achieved higher antibody levels after receiving the mRNA vaccine.”

In the post hoc analysis, patients with relapsing MS were given evobrutinib 75 mg two times a day, and two doses of mRNA COVID-19 vaccination. The specific antibodies to COVID-19, immunoglobulin G anti-S1 and anti-S2, were measured with an indirect chemiluminescence immunoassay.1 Pre-dose samples used were from the latest available prior to the first mRNA vaccine dose while the post-dose sample was available more than or 28 days after second mRNA vaccine dose.

“Prior research resulted in patients who had systemic lupus erythematosus and received evobrutinib had the potential to mount a humoral response to the seasonal influenza vaccination” Bar-Or et al noted.

The post-dose observed time ranged from 4.9 to 15.1 weeks following vaccination. The majority of patients had their antibody assessment for the second dose done more than 8 weeks after administration. Researchers observed that there was a lower antibody level present with an increased time between the second dose of the mRNA vaccine and the assessment for the antibodies.

The baseline mean for the age of the patients was 44.6 (±10.1) years of age and 79.2% of the cohort were women. Additionally, the mean for evobrutinib exposure pre-vaccination was 105.8 weeks. Patients (n = 22) who were seronegative or positive had at least a 10-60-fold induction of S1/S2 IgG antibody levels from pre- to post-vaccination. The median fold change for the S1/S2 IgG antibody levels was 32.6-fold for total patients, 34.2-fold for seronegative patients and 18.3-fold for seropositive patients.

Bar-Or and colleagues wrote that patients with, “RMS treated with evobrutinib were able to mount an antibody response to two doses of mRNA COVID-19 vaccination. The marked increase in antibody response in seronegative and seropositive patients demonstrates a preserved response to novel and recall antigens in [patients with] RMS undergoing BTKi with evobrutinib.”

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REFERENCES
1. Bar-Or A, Cross A.H., Cunningham A et al. Immune response following mRNA COVID-19 vaccination in patients with multiple sclerosis treated with the Bruton’s tyrosine kinase inhibitor evobrutinib. Presented at: 2022 ECTRIMS Congress; October 26-28; Amsterdam, Netherlands. Late Breaker EPoster 1188