Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: who gains from it?

Background: Although two doses of Covid-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multiCenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: 473 pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95%CI=14.3-100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95%CI=8.3-50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95%CI=1.2-4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab/ocrelizumab showed a 2.3-fold lower gain (95%CI=1.4-3.8; p = 0.001), whereas, in contrast, those on fingolimod showed a 1.7-fold higher gain (95%CI: 1.1-2.7; p = 0.012), compared to patients treated with other DMTs. Conclusions All pwMS increased their serum SARS-CoV-2 antibodies levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical 'protective threshold' for risk of infection identified in the CovaXiMS study (> 659 BAU/mL), whereas for patients treated with fingolimod this value was significantly closer to the cut-off.