ABSTRACT
Introduction: Recently developed SARS-CoV-2 mRNA vaccines have been shown to efficiently protect healthy individuals against COVID-19 and contribute greatly towards fighting the COVID- 19 pandemic. Aim(s): As only limited data is available for Multiple Sclerosis (MS) patients with immunosuppressive treatment, this study aims to understand the impact of ofatumumab treatment on the development of cellular and humoral immune responses to initial and booster SARS-CoV-2 mRNA vaccines. Method(s): KYRIOS is a prospective, open-label, two-cohort study including 34 MS patients at 8 sites in Germany. Patients receive initial or booster SARS-CoV-2 mRNA vaccination either before (cohort 1) or at least 4 weeks after starting ofatumumab treatment (cohort 2). As primary endpoint, the impact of ofatumumab treatment on development of SARS-CoV-2 reactive T-cells will be evaluated. Additionally, neutralizing antibodies will be assessed, and the immune responses will be monitored and phenotypically described for up to 18 months. Result(s): Interim analysis will show the complete primary endpoint results of the KYRIOS study. All patients vaccinated during continuous ofatumumab treatment (5/5) developed an immune response as soon as one week after initial vaccination cycle. While the extent of T-cell response was not affected in ofatumumab treated patients, neutralizing antibodies titers were lower compared to the control group. After the first booster vaccine, the majority of ofatumumab patients (n=15) showed an increase in neutralizing antibodies to a comparable extend as the control group (n=8). Data show that seroconversion during continuous ofatumumab treatment is possible. In general, this analysis confirms first positive interim analysis data presented at AAN 2022. Conclusion(s): KYRIOS data demonstrate that ofatumumab treated patients can mount specific immune responses towards SARSCoV- 2 mRNA vaccines. The presented data further emphasize the importance of considering both, humoral and cellular immune response, for interpretation of vaccine efficacy and the importance of booster vaccines in immunocompromised patients.
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
Background and aims: Initial and booster vaccination with the newly developed SARS-CoV-2 mRNA vaccines efficiently protect healthy individuals against COVID-19. As only limited data is available for Multiple Sclerosis (MS) patients with immunosuppressive treatment, this study aims to comprehend the impact of ofatumumab treatment on mounting cellular and humoral immune responses to SARS-CoV-2 mRNA vaccines. Methods: KYRIOS is an open-label, two-cohort study including 40 MS patients at 8 sites in Germany. Patients receive initial or booster SARS-CoV-2 mRNA vaccination either before (cohort 1) or at least 4 weeks after starting ofatumumab treatment (cohort 2). The impact of ofatumumab treatment on development of SARS-CoV-2 reactive T-cells (primary endpoint) and neutralizing antibodies (secondary endpoint) will be evaluated. Furthermore, immune responses will be monitored and phenotypically described for up to 18 months. Results: Results of an interim analysis show that SARSCoV- 2 mRNA vaccines can induce cellular and humoral immune responses in ofatumumab-treated patients. Immune responses could be detected as soon as 1 week after the initial vaccination cycle for all patients receiving their initial SARS-CoV-2 vaccines during stable ofatumumab treatment (n=4) or before ofatumumab initiation (n=5). The interim analysis further shows the effect of ofatumumab treatment on development of immune responses after booster vaccines (n=23). Conclusion: The KYRIOS study demonstrates for the first time that ofatumumab treated patients can mount specific immune responses towards SARS-CoV-2 mRNA vaccines. The results further suggest that both, humoral and cellular immune response, need to be considered for interpretation of vaccine efficacy and are in line with other recently published studies.
ABSTRACT
Objective: This study aims at understanding the impact of ofatumumab treatment on the development of cellular and humoral immune responses to initial and booster SARS-CoV-2 mRNA vaccines. Background: Recently developed SARS-CoV-2 mRNA vaccines have been shown to efficiently protect healthy individuals against COVID-19 and contribute greatly towards fighting the COVID-19 pandemic. However, only limited data is available about vaccine-induced immune responses in immunosuppressed patients. Design/Methods: KYRIOS is an open-label, prospective, two-cohort study at eight sites in Germany including 40 MS patients who receive SARS-CoV-2 mRNA vaccination either before starting ofatumumab treatment (cohort 1) or during stable ofatumumab treatment for at least 4 weeks (cohort 2). The impact of ofatumumab treatment on the proportion of patients having established SARS-CoV-2 reactive T-cells (primary endpoint) and developing SARS-CoV-2 neutralizing antibodies (secondary endpoint) after initial and booster vaccination will be assessed. Additionally, cellular and humoral immune responses will be monitored for up to 18 months and cellular response will be further described by immunophenotyping. Results: Results of this second interim analysis show the efficacy of SARS-CoV-2 mRNA vaccines to induce cellular and humoral immune responses in MS patients depending on the timing of ofatumumab treatment initiation. First data indicate that in patients vaccinated during stable ofatumumab treatment, specific immune response is detectable as soon as 1 week after the initial vaccination cycle and further increases afterwards. Conclusions: KYRIOS data show for the first time that patients vaccinated during stable ofatumumab treatment can mount immune responses to SARS-CoV-2 mRNA vaccines. The presented data further emphasize the importance of considering both, humoral and cellular immune response, for interpretation of vaccine efficacy.
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.
ABSTRACT
Introduction: Development of SARS-CoV-2 vaccines was a key milestone in fighting the COVID-19 pandemic. However, little is known about the efficacy of these vaccines in patients with Multiple Sclerosis (MS) treated with anti-CD20 therapies. Aims: This study aims to understand the impact of ofatumumab treatment on mounting cellular and humoral immune responses to SARS-CoV-2 mRNA vaccination. Methods: KYRIOS is a two-cohort, open-label, prospective study including 40 RMS patients at eight sites in Germany. Enrolled patients receive SARS-CoV-2 mRNA vaccination either before initiation of ofatumumab treatment (cohort 1) or during stable ofatumumab treatment for at least 4 weeks (cohort 2). As primary endpoint, the proportion of patients having established SARSCoV- 2 reactive T-cells one week after the second vaccine will be assessed. The established T-cell response will further be described by immunophenotyping and the proportion of patients achieving seroconversion (defined as the presence of serum SARS-CoV-2 neutralizing antibodies in patients negative for this parameter at baseline) will be evaluated as secondary endpoints. Results: Results of an interim analysis will show the effect of timing of SARS-CoV-2 mRNA vaccines on development of SARSCoV- 2 specific T-cells as well as neutralizing antibodies in MS patients receiving ofatumumab. The detailed characterization of SARS-CoV-2 specific T-cells further provides insights regarding the effect of B-cell depletion on the mode of action of mRNA vaccines. Conclusion: Data gathered by this study can support informed decision making with regards to the coordination of SARSCoV- 2 mRNA vaccination and treatment of MS patients with ofatumumab.