Humoral immune response to COVID-19 mRNA vaccines in patients with relapsing multiple sclerosis treated with ofatumumab

ABSTRACT

Introduction: Ofatumumab (OMB), a fully-human anti-CD20 monoclonal antibody (Ab), is indicated for the treatment of adults with relapsing multiple sclerosis (RMS). As OMB induces B-cell depletion, it is important to understand if OMB-treated patients (pts) can mount a protective immune response to the COVID-19 vaccine. Objective(s) Assess humoral immune response (HIR) to mRNA COVID-19 vaccines in OMB-treated pts with RMS. Method(s) This was an open-label, single-arm, multicentre, prospective pilot study (NCT04847596) of pts with RMS aged 18-55y receiving 2 doses of an mRNA COVID-19 vaccine after treatment with OMB 20mg for >=1mo. Pts who received a 3rd/ booster vaccine dose were also eligible. Exclusion criteria included prior COVID-19 diagnosis, recent major infections and prior sphingosine 1-phosphate receptor modulator or natalizumab treatment. The 1st post-vaccination immune assay was performed >=14d after full vaccination course (2 or 3 doses), with the 2nd assay conducted 90d after the 1st assessment (assays conducted by local laboratories). Primary endpoint was proportion of pts achieving an HIR, defined as a positive response on the SARS-CoV-2 qualitative IgG Ab assay. Secondary endpoints were adverse events (AEs) and serious AEs. Result(s) 26 pts (median [range] age 42 [27-54]y) were included;81% were female, 96% were White and 35% were Hispanic/Latino. Median (range) OMB treatment duration at screening was 237d (50-364). 15 pts (58%) received 2 vaccine doses;11 (42%) received a 3rd/booster dose. HIR to COVID-19 vaccines was achieved by 14/26 pts (54% [95%CI 33%-73%]) at the 1st post-vaccination assay. In pts who received a booster;7/10 achieved an HIR and 6/7 aged <50y achieved HIR. Prior ocrelizumab use or age >=50y led to a decreased HIR while length of OMB treatment and COVID-19 mRNA vaccine type did not impact HIR. At the 2nd assay, 13/26 pts (50% [95%CI 30%-70%]) achieved an HIR (10 pts maintained and 3 additional pts achieved HIR;2 pts who achieved HIR at the 1st assay were negative at the 2nd assay;2 pts had missing assays). Overall, 5/26 pts (19%) reported >=1 AEs, including COVID-19 infection (n=4), herpes zoster infection (n=1), S. pharyngitis (n=1) and headache (n=1). No serious AEs were reported. Conclusion(s) These findings suggest that most OMB-treated pts with RMS mount an HIR after COVID-19 mRNA vaccination and may help inform the coordination of vaccination and treatment of RMS pts with OMB.