Background: To determine the effect of disease-modifying
therapies (DMT) on humoral postvaccine seroconversion, long-term humoral response, and
breakthrough COVID-19 infections in persons with
multiple sclerosis (PwMS) and other
neuroinflammatory disorders. Methods: A total of 757 PwMS and other
neuroinflammatory disorders were recruited in two MS centers and vaccinated with one of the FDA-approved
vaccines (
BNT162b2,
mRNA-1273,
Ad26.COV2.S). The primary outcomes are the rate of humoral postvaccine seroconversion and anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2)
immunoglobulin G (
IgG) differences between patients on different DMTs. Secondary measures include
breakthrough infections and humoral response after six months. Other outcomes include differences in
vaccine response between
SARS-CoV-2 vaccines and the effects of age and comorbidities on the
vaccine response. Results: A total of 465 (68.4%) PwMS and 55 (74.3%) patients with
neuroinflammatory diseases were seropositive at 4−12 weeks after vaccination. A significant difference in seroconversion based on the DMT used at the time of vaccination (p < 0.001) was observed, with the lowest rates seen in patients treated with anti-CD20
antibodies (23.2%) and
sphingosine-1-phosphate modulators (S1P) (30.8%). In seropositive patients, there was a significant decrease in anti-SARS
IgG from mean 20.0 to 4.7 at six months (p = 0.004). Thirty-nine patients had
breakthrough infection, but only two seronegative patients required hospitalization.
mRNA vaccines resulted in significantly greater seroconversion compared to
Ad26.COV2.S (p < 0.001). Older age and presence of cardiovascular comorbidities were associated with lower anti-SARS
IgG (p = 0.021 and p = 0.003, respectively) Conclusions: PwMS and
neuroinflammatory disorders treated with anti-CD20 and S1P medications have lower humoral response after anti-SARS-CoV-2 vaccination, even after booster dose. Waning of the humoral response puts vaccinated PwMS at a greater risk of
COVID-19 breakthrough.