ABSTRACT
Background and aims: SARS-CoV-2 mRNA vaccines are a key factor for fighting the COVID-19 pandemic across the globe. However, data are lacking on the efficacy of these vaccines to induce cellular and humoral immune responses in patients with secondary progressive multiple sclerosis (SPMS) on disease-modifying therapies (DMTs) both over time and after a booster vaccination. Methods: AMA-VACC is prospective, open-label, threecohort study including 41 multiple sclerosis patients at ten sites in Germany. Cohort 1 receives SARS-CoV-2 mRNA vaccination during continuous siponimod treatment, cohort 2 interrupts siponimod treatment for the purpose of a full vaccination cycle and cohort 3 is vaccinated during continuous treatment with first-line DMTs (dimethylfumarate, glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine. Development of neutralizing antibodies (primary endpoint) as well as detection of SARS-CoV-2 specific T-cells (secondary endpoint) are assessed after initial and booster vaccination and monitored for up to 6 months. Results: Results of previous interim analysis showed that the majority of patients treated with siponimod can mount an immune response after SARS-CoV-2 mRNA vaccination. Here, longitudinal data will be presented describing for the first time the level of cellular and humoral immune response for up to 6 months after vaccination and the effect of booster vaccines in siponimod treated patients. Conclusion: This analysis will provide data on the maintenance of humoral and cellular immune response after SARS-CoV-2 vaccination in siponimod treated patients and enable physicians and patients to make an informed decision on the coordination of SARS-CoV-2 mRNA (booster) vaccination and SPMS treatment.
ABSTRACT
Objective: We are aiming 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: SARS-CoV-2 mRNA vaccines are a key factor fighting the COVID-19 pandemic across the globe. However, data are lacking on 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, first-line DMT or without treatment in clinical routine. Cohort 1 receives SARS-CoV-2 mRNA vaccination while continuing their current siponimod treatment, cohort 2 interrupts siponimod treatment for the purpose of a full vaccination cycle and cohort 3 receives vaccination during continuous treatment with first-line DMTs (glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine. Primary endpoint is the rate of patients achieving seroconversion assessed by detection of serum neutralizing antibodies one week after SARS-CoV-2 mRNA vaccination. Furthermore, development and maintenance of SARS-CoV-2 specific T-cells is evaluated in all patients. Both parameters are analyzed in week one and month one and six after initial vaccination cycle and one month after a potential booster vaccination. Results: After a positive first interim analysis showing both SARS-CoV-2 neutralizing antibodies and T-cell responses one week after complete vaccination in siponimod patients data will be available in early 2022 for all patients at week one and later time points including first booster vaccinations. If possible, AMA-VACC results will be compared to findings from other clinical SARS-CoV-2 vaccination studies in patients with MS. Conclusions: This analysis will provide first longitudinal data on the immune response after SARS-CoV-2 mRNA vaccination in siponimod treated SPMS patients and enable physicians and patients to make an informed decision on the coordination of SARS-CoV-2 mRNA vaccination and SPMS treatment.
ABSTRACT
Introduction: SARS-CoV-2 mRNA vaccines are a key factor for fighting the COVID-19 pandemic across the globe. However, data are lacking on the efficacy of vaccination in patients with secondary progressive multiple sclerosis (SPMS) on disease-modifying therapies (DMTs). Aim: We are aiming to understand the cellular and humoral immune responses to SARS-CoV-2 mRNA vaccines depending on the timing of vaccination and SPMS treatment. Methods: AMA-VACC is clinical open-label, three-cohort, prospective study at up to ten sites in Germany including 60 multiple sclerosis patients currently treated with siponimod, any first-line DMT or without treatment at all in clinical routine. Cohort 1 receives SARS-CoV-2 mRNA vaccination while continuing their current siponimod treatment, cohort 2 interrupts siponimod treatment for for the purpose of a full vaccination cycle and cohort 3 receives vaccination during continuous treatment with first-line DMTs (dimethylfumarate, glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine. Primary endpoint is the rate of patients achieving seroconversion assessed by detection of neutralizing antibodies after SARS-CoV-2 mRNA vaccination. Furthermore, development of SARS-CoV-2 specific T-cells is evaluated in all patients. Results: Data will be available in summer 2021 and will be presented together with the detailed study design. If possible, AMAVACC results will be compared to findings from other clinical SARS-CoV-2 vaccination studies in patients with MS. Conclusion: This analysis will provide first data on the immune response after SARS-CoV-2 mRNA vaccination in patients with SPMS treated with siponimod and enable physicians to make an informed decision on the coordination of SARS-CoV-2 mRNA vaccination and SPMS treatment.