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

Aliya Jaber; Meera Patel; Andrew Sylvester; Mary Yarussi; J Tamar Kalina; Jason P Mendoza; Robin L Avila; Matthew A Tremblay

doi:10.1007/s40120-023-00448-x

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

Neurol Ther. 2023 Apr;12(2):687-700. doi: 10.1007/s40120-023-00448-x. Epub 2023 Feb 16.

Authors

Aliya Jaber¹, Meera Patel¹, Andrew Sylvester¹, Mary Yarussi¹, J Tamar Kalina², Jason P Mendoza², Robin L Avila², Matthew A Tremblay³

Affiliations

¹ Multiple Sclerosis Comprehensive Care Center, RWJ Barnabas Health, Livingston, NJ, USA.
² Biogen, Weston, MA, USA.
³ Multiple Sclerosis Comprehensive Care Center, RWJ Barnabas Health, Livingston, NJ, USA. Matthew.Tremblay@rwjbh.org.

Abstract

Background: 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.

Methods: 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 interferon beta (n = 6); ages 18-65 years inclusive; stable on DMT for at least 6 months. Responder rates, anti-SARS-CoV-2 spike receptor-binding domain IgG (anti-RBD) geometric mean titers (GMTs), antigen-specific T cells, and vaccination-related adverse events were evaluated at baseline and 8, 24, 36, and 48 weeks after first mRNA-1273 (Moderna) dose.

Results: At 8 weeks post vaccination, all natalizumab-, fumarate-, and interferon beta-treated participants generated detectable anti-RBD IgG titers, compared to only 25% of the ocrelizumab cohort. At 24 and 36 weeks post vaccination, natalizumab-, fumarate-, and interferon beta-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 24 weeks post vaccination for the non-ocrelizumab-treated participants, with no significant difference between groups. At 36 weeks post vaccination, ocrelizumab-treated participants had higher proportions of spike-specific T cells compared to other treatment groups. Vaccine-associated side effects were highest in the ocrelizumab arm for most symptoms.

Conclusions: These results suggest that humoral response to mRNA-1273 COVID-19 vaccine is preserved and similar in PwMS treated with natalizumab, fumarate, and interferon beta, but muted with ocrelizumab. All DMTs had preserved T cell response, including the ocrelizumab cohort, which also had a greater risk of vaccine-related side effects.

Keywords: COVID-19; Dimethyl fumarate; Interferon beta; Multiple sclerosis; Natalizumab; Ocrelizumab; Vaccine response.