Immune Response to COVID-19 Vaccine in People with Multiple Sclerosis Treated with Dimethyl Fumarate, Diroximel Fumarate, Natalizumab, Ocrelizumab or Interferon Therapy

Background: COVID-19 is a potentially fatal respiratory illness that has claimed the lives of over 800,000 people in the United States and 5.6 million people worldwide as of January 2022. Mass vaccination is one of the best tools available to curtail the pandemic. Some disease modifying therapies (DMTs) used to treat multiple sclerosis (MS) impair immune responses to vaccines. Data across multiple DMTs are needed to understand both humoral and cellular immune responses to COVID-19 vaccines in people with MS (PwMS).

Objectives: This analysis evaluates and compares the effect of DMTs on immune response to mRNA vaccines for prevention of COVID-19.

Methods: This open-label prospective observational study recruited 45 participants treated with natalizumab (n=12), ocrelizumab (n=16), interferon-beta (n=6), and dimethyl or diroximel fumarate (n=11) stably for at least 6 months and ages 18–65 years (inclusive). Humoral response was assessed by measuring serum anti-RBD (SARS-CoV-2 spike glycoprotein) IgG levels (sCOVg, Siemens Healthineers) at 8, 24, and 36 weeks after 1^st dose of mRNA-1273 (Moderna). Cellular response was assessed by evaluation for antigen-specific T cells using T-Cell Receptor sequencing (ImmunoSEQ T-MAP COVID, Adaptive Biotechnologies) at 36-weeks after 1^st dose of mRNA-1273.

Results: At 8-weeks post-vaccination, all natalizumab, interferon, and fumarate-treated patients generated detectable anti-RBD IgG titers with similar geometric mean titers (GMT) between these treatments, which continued to be detectable at 24 weeks post-vaccination. However, at 8 weeks only 25% of participants on ocrelizumab generated detectable anti-RBD titers and no (0%) ocrelizumab-treated patients had detectable anti-RBD IgG titers at 24 weeks. An 81.5% reduction in anti-RBD GMT was observed for non-ocrelizumab participants with similar GMT at 24 weeks. GMT and cellular immune response at 36-weeks will be presented.

Conclusions: These results suggest that humoral response to mRNA-1273 COVID-19 vaccine is preserved and similar in PwMS treated with natalizumab, interferon, and fumarate, while dramatically muted in PwMS treated with ocrelizumab. The relative importance of both humoral and cell-mediated immunity to SARS-CoV-2 in the context of DMTs is crucial to understand, especially for PwMS who failed to seroconvert.

Study Support: Biogen.