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

Abstract

Some multiple sclerosis (MS) disease-modifying therapies (DMTs) impair responses to vaccines, emphasizing the importance of understanding COVID-19 vaccine immune responses in people with MS (PwMS) receiving different DMTs. This prospective, open-label observational study enrolled 45 participants treated with natalizumab (n = 12), ocrelizumab (n = 16), fumarates (dimethyl fumarate or diroximel fumarate, n = 11), or interferonbeta (n = 6); ages 18-65years inclusive; stable on DMT for at least 6months. Responder rates, anti-SARS-CoV-2 spike receptor-binding domain IgG (anti-RBD) geometric mean titers (GMTs), antigen-specific Tcells, and vaccination-related adverse events were evaluated at baseline and 8, 24, 36, and 48weeks after first mRNA-1273 (Moderna) dose. At 8weeks post vaccination, all natalizumab-, fumarate-, and interferonbeta-treated participants generated detectable anti-RBD IgG titers, compared to only 25% of the ocrelizumab cohort. At 24 and 36weeks post vaccination, natalizumab-, fumarate-, and interferonbeta-treated participants continued to demonstrate detectable anti-RBD IgG titers, whereas participants receiving ocrelizumab did not. Anti-RBD GMTs decreased 81.5% between 8 and 24weeks post vaccination for the non-ocrelizumab-treated participants, with no significant difference between groups. At 36weeks post vaccination, ocrelizumab-treated participants had higher proportions of spike-specific Tcells compared to other treatment groups. Vaccine-associated side effects were highest in the ocrelizumab arm for most symptoms. These results suggest that humoral response to mRNA-1273 COVID-19 vaccine is preserved and similar in PwMS treated with natalizumab, fumarate, and interferonbeta, but muted with ocrelizumab. All DMTs had preserved Tcell response, including the ocrelizumab cohort, which also had a greater risk of vaccine-related side effects.