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

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.

IV immunoglobulin confounds JC virus antibody serostatus determination.

OBJECTIVE: To determine the impact of therapeutic infusion of IV immunoglobulin (IVIg) on John Cunningham virus antibody (JCV Ab) serostatus and level in serum. METHODS: We carried out a retrospective analysis of serum levels of JCV Ab among STRATIFY-2 trial enrollees from 2 multiple sclerosis centers who were exposed to IVIg during the trial. For the subset of eligible patients, we estimated mean linear trends while on IVIg and after stopping IVIg with a linear mixed-effects model. RESULTS: The JCV Ab seropositivity rate in the group of patients that was recently exposed to IVIg was 100%, which is significantly higher than in the IVIg-naive population (58%, p < 0.001). The seropositivity rate in the patient group with remote IVIg exposure was similar to that in the IVIg-naive population (67%, p = 0.68, Fisher exact test). The slope of the linear trend line after stopping IVIg decreased significantly by -0.310 units per 100 days (95% confidence interval, -0.611 to -0.008; p = 0.04). CONCLUSIONS: Recent IVIg exposure is invariably associated with JCV Ab seropositivity. After stopping IVIg, JCV Ab levels tend to decrease with time, and seroreversion to innately Ab-negative status can occur.