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.
ABSTRACT
Introduction: Ofatumumab (OMB), a fully human anti-CD20 monoclonal antibody, is indicated for the treatment of adults with relapsing multiple sclerosis (RMS) in the US. Given the ongoing COVID-19 global pandemic, it is important to assess if OMBtreated patients can mount a protective immune response to the COVID-19 vaccine. Objectives/Aims: To assess immune response to non-live COVID-19 mRNA vaccines (Pfizer or Moderna) in RMS patients treated with subcutaneous OMB 20 mg monthly compared to those on interferon or glatiramer acetate. Methods: This is a 3-cohort, multicenter, prospective study in RMS patients (aged 18-55) receiving the mRNA COVID-19 vaccine (NCT04878211). Patients with prior COVID-19 diagnosis, recent infections, and prior treatment with other immunomodulatory disease-modifying therapies will be excluded. Cohort 1 will receive full course (2 doses) of vaccine ≥2 weeks prior to starting OMB. Cohort 2 will receive the full course of vaccine ≥4 weeks after starting OMB. Cohort 3 will receive the full course of vaccine ≥4 weeks after starting interferon or glatiramer acetate. Patients will continue taking their prescribed therapy per their current dosing schedule throughout treatment period (360 days after completion of full course vaccine). All groups will undergo serologic testing prior to vaccination and 14 days after 2nd vaccine dose. Primary endpoint is positive SARS-CoV-2 qualitative IgG antibody assay 14 days after full course vaccination. Key secondary endpoints include immune response to vaccine at other timepoints, immune conversion to vaccine (SARS-CoV-2 qualitative/ quantitative IgG antibody assay), SARS-CoV-2 neutralizing IgG antibody development, and adverse events (AEs) and serious AEs associated with OMB treatment. Exploratory endpoints include frequency of IFNγ positive CD4+ or CD8+ T cells, and T cell reactivity, after stimulation with SARS-CoV-2 peptide. Results: This study plans to enroll up to 66 RMS patients (up to 22 per cohort) at up to 30 US centers. The planned first patient first visit is on May 31, 2021 and study completion is expected by Q4 2022. An interim analysis will be performed once Cohorts 2 and 3 each have ≥10 patients that have had serum drawn 14 days after full course vaccination. Conclusions: This study will contribute to a better understanding of immune responses that occur in OMB-treated RMS patients given a COVID-19 mRNA vaccine.