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

by Selleckchem | May 07 2023

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.

Comments：

Summary:

This is a prospective, open-label observational study that evaluated the immune response to the mRNA-1273 COVID-19 vaccine in people with multiple sclerosis (MS) receiving different disease-modifying therapies (DMTs). The study included 45 participants treated with natalizumab, ocrelizumab, fumarates (dimethyl fumarate or diroximel fumarate), or interferon beta. The results showed that the humoral response to the vaccine was preserved and similar in participants treated with natalizumab, fumarates, 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.

Key findings:

At 8 weeks post vaccination, all natalizumab-, fumarate-, and interferon beta-treated participants generated detectable anti-SARS-CoV-2 spike receptor-binding domain IgG (anti-RBD) 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 geometric mean titers (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.
Interpretation:

The study provides important information on the immune response to the mRNA-1273 COVID-19 vaccine in people with MS receiving different DMTs. The findings suggest that the humoral response to the vaccine is preserved and similar in participants treated with natalizumab, fumarates, and interferon beta, but muted with ocrelizumab. This is consistent with previous studies that have shown impaired vaccine responses in people receiving anti-CD20 therapies like ocrelizumab. The study also shows that all DMTs had preserved T cell response, which is important for long-term immunity. However, the ocrelizumab cohort had a greater risk of vaccine-related side effects, which should be taken into consideration when vaccinating people with MS receiving this therapy. Overall, these findings highlight the importance of understanding vaccine responses in people with MS receiving different DMTs and tailoring vaccination strategies accordingly.