Third dose of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies

ABSTRACT

Introduction: In patients with Multiple Sclerosis (pwMS) treated with anti-CD20 treatment or fingolimod it was observed a reduced humoral response after the second dose of mRNA-based SARS-CoV-2 vaccines.It is important to evaluate the effect of the third dose in these groups of patients. Aim(s) To describe the demographical and clinical characteristics of pwMS which received the third dose of Covid-19 vaccine and compare within patients the antibody levels measured just before the third dose with the same assessment executed one month after the third dose. Method(s) The CovaXiMS study is a prospective study for the evaluation of immunogenicity of anti-SARS-CoV2 vaccines in pwMS. Adult pwMS who have performed a third dose of SARSCoVv- 2 vaccination were included in the study. The main endpoint is the change in the antibody levels from six months after the second dose vs one month following the third dose, by considering actual DMTs. Result(s) Out of 1881 enrolled pwMS, 318 (16.9%) received the third dose (83.6% mRNA BNT162b2 and 16.4%mRNA-1273) with a complete assessment of antibody levels before and after the injection. Of them, 236 (74.2%) were females, with a mean age of 48.1 (SD12.43). Median EDSS was 2.0 [IQR 1.0-3.5], 8 (2.5%) pwMS recorded at least one relapse in the three months before enrollment, 271 (85.2%) were RRMS, 27 (8.5%) SPMS, and 20 (6.3%) PPMS. Fifty-six (17.6%) pwMS were on fingolimond, 52 (16.4%) on anti-CD20, and 210 (66.0%) on other drugs. Median antibody level (BAU/ml) measured just before the third dose was 0.0 for pwMS treated with anti-CD20, 35.7 for pwMS on fingolimod and 680.9 for pwMS with other therapies. One month after the third dose the median change in the antidoby levels (BAU/ml) was +0.6 for pwMS on anti-CD20, +694.6 for pwMS on fingolimod and +13879.4 BAU/ml for pwMS on other DMTs (p<0.001). Considering 659 BAU/mL as the best cut-off indicating a protective antibody level, as suggested by previous literature, 98% of pwMS on other DMTs showed a value above this value, 55% of pwMS on fingolimod, and 23% of pwMS on anti-CD20 (p<0.001). Conclusion(s) After the third dose, a significant increase in antidoby levels was detected in patients with MS. Patients in fingolimod and anti-CD20 had an increase significantly lower than patients in other drugs, but 55% of patients on fingolimod reached an antibody level considered as protective.