The immune response to SARS-COV-2 MRNA vaccines in siponimod-treated patients with secondary progressive multiple sclerosis

ABSTRACT

Objective: We aimed to understand the longitudinal cellular and humoral immune responses to SARS-CoV-2 mRNA vaccines depending on the timing of vaccination and SPMS treatment. Background(s) SARS-CoV-2 mRNA vaccines are a key factor in fighting the COVID-19 pandemic. However, data are lacking on the efficacy of vaccination in patients with secondary progressive multiple sclerosis (SPMS) on disease-modifying therapies (DMTs), both over time and after a booster vaccination. Design/Methods: AMA-VACC is an open-label, three-cohort, prospective study in Germany with 41 multiple sclerosis patients currently treated with siponimod, any first-line DMT or without treatment in clinical routine. Cohort 1 received SARS-CoV-2 mRNA vaccination while continuing current siponimod treatment, cohort 2 interrupted siponimod treatment for the purpose of a full vaccination cycle, and cohort 3 received vaccination during continuous treatment with first-line DMTs (glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine. The primary endpoint was the rate of patients achieving seroconversion assessed by detection of serum neutralizing antibodies 1 week after SARS-CoV-2 mRNA vaccination. Furthermore, development and maintenance of SARS-CoV-2 specific T-cells was evaluated in all patients. Both parameters were analyzed in week one and months one and six after the initial vaccination cycle and 1 month after a potential booster vaccination. Result(s) After a positive first interim analysis showing both SARSCoV- 2 neutralizing antibodies and T-cell responses 1 week after complete vaccination in siponimod patients, data will be available in early 2022 for all patients at week one and later timepoints, including first booster vaccinations. Conclusion(s) This analysis will provide the first longitudinal data on the immune response after SARS-CoV-2 mRNA vaccination in siponimodtreated SPMS patients and enable physicians and patients to make an informed decision on the coordination of SARS-CoV-2 mRNA vaccination and SPMS treatment.