Assessing the immune response to SARS-CoV-2 mRNA vaccines in siponimod-treated patients: a nonrandomized controlled clinical trial (AMA-VACC)

Tjalf Ziemssen; Marie Groth; Benedict Rauser; Tobias Bopp

doi:10.1177/17562864221135305

Assessing the immune response to SARS-CoV-2 mRNA vaccines in siponimod-treated patients: a nonrandomized controlled clinical trial (AMA-VACC)

Ther Adv Neurol Disord. 2022 Nov 8:15:17562864221135305. doi: 10.1177/17562864221135305. eCollection 2022.

Authors

Tjalf Ziemssen¹, Marie Groth², Benedict Rauser², Tobias Bopp³

Affiliations

¹ Department of Neurology, Center of Clinical Neuroscience, Carl Gustav Carus University Clinic, University Hospital of Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
² Novartis Pharma GmbH, Nuremberg, Germany.
³ Institute for Immunology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Abstract

Background: Systematic data are lacking on the immune response toward SARS-CoV-2 mRNA vaccination in SPMS patients on disease-modifying therapies (DMTs).

Objective: The AMA-VACC clinical trial was designed to characterize immune responses to SARS-CoV-2 mRNA vaccines in siponimod-treated SPMS patients.

Design: AMA-VACC is an ongoing three-cohort, multicenter, open-label, prospective clinical study.

Methods: The study included patients at risk for SPMS or patients with SPMS diagnosis. Patients received SARS-CoV-2 mRNA vaccine as part of their clinical routine during ongoing siponimod treatment (cohort 1), during siponimod treatment interruption (cohort 2), or while on dimethyl fumarate, glatiramer acetate, beta-interferons, teriflunomide, or no current therapy (cohort 3). SARS-CoV-2-specific neutralizing antibodies and T-cell responses were measured 1 week and 1 month after the second dose of vaccination.

Results: In total, 17 patients, 4 patients, and 20 patients were recruited into cohorts 1, 2, and 3, respectively. The primary endpoint of seroconversion for SARS-CoV-2-neutralizing antibodies at week 1 was reached by 52.9%, 75.0%, and 90.0% of patients in cohorts 1, 2, and 3, respectively. For 64.7% of patients in cohort 1, all patients in cohort 2, and 95% of patients in cohort 3, seroconversion was observed at either week 1 or month 1 or both time points. After 1 week, 71.4% of cohort 1, 75.0% of cohort 2, and 85.0% of cohort 3 were positive for either SARS-CoV-2-neutralizing antibodies or SARS-CoV-2-specific T-cells or both. After 1 month, the rates were 56.3%, 100.0%, and 95.0%, respectively.

Conclusion: The study shows that the majority of siponimod patients mount humoral and cellular immune response under continuous siponimod treatment. The data do not sufficiently support interruption of treatment for the purpose of vaccination.

Registration: EU Clinical Trials Register: EudraCT 2020-005752-38 (www.clinicaltrialsregister.eu); ClinicalTrials.gov: NCT04792567 (https://clinicaltrials.gov).

Keywords: COVID-19 vaccination; T-cell response; disease-modifying therapy; neutralizing antibodies; secondary progressive multiple sclerosis.

Associated data

ClinicalTrials.gov/NCT04792567