The primary objective of this study is to characterize the antibody response to seasonal influenza vaccine, in patients with active RRMS, treated with cladribine, compared to control individuals with basic immunomodulatory treatment. Serum antibody titers against the respective pathogen will be assessed prior to and 6 to 8 months following vaccination.
Study Type
OBSERVATIONAL
Enrollment
260
Seasonal Influenza vaccine: according to the latest SmPC and according to national guidelines (published by the Standing Committee on Vaccination (STIKO)).
Medical Faculty, Heinrich-Heine-University
Düsseldorf, North Rhine-Westphalia, Germany
RECRUITINGProportion who achieve seroprotection
The capacity of influenza vaccine to elicit a measurable immune response (immunogenicity) when it is administered (i) shortly (at least 4-6 weeks) before cladribine initiation (cohort 1), (ii) 3 to 4 months after cladribine initiation (cohort 2) (iii) shortly (at least 4-6 weeks) before second cladribine administration (cohort 3) and (iv) in patients who have already received the second cycle of cladribine tablets (3 to 4 months after second cycle; cohort 4), compared to RRMS patients treated with basic DMTs (cohort 5). Efficacy is measured as proportion of patients who achieve seroprotection (specific hemagglutination inhibition (HI) titers \> 1:40)).
Time frame: 6 months
Fraction with 2-fold increase of HI titers
Proportion of patients who achieve a 2-fold increase in specific HI titers at 6 to 8 months post-immunization
Time frame: 6 months
Fraction with 4-fold increase of HI titers
Proportion of patients who achieve a 4-fold increase in specific HI titers at 6 months post-immunization
Time frame: 6 months
Seroconversion rate
Proportion of patients with seroconversion (i.e., a pre-vaccination antibody titer \< 10 and a post-vaccination HI titer \> 40)
Time frame: 6 months
Mean antibody titers
Geometric mean antibody titers (GMTs) and geometric mean antibody ratios (GMRs, post-vaccination:pre-vaccination) prior and 6 months after vaccination
Time frame: 6 months
Cellular immune responses
Flow cytometry analysis, which will include (but is not limited to) the following cells: Total B cells (CD19 positive), B-cell subsets, e.g., memory B cells, naïve B cells, plasma cells; Total T cell (CD3 positive) and T cell subsets, e.g. T helper cells, cytotoxic lymphocyte T cells
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Time frame: 6 months
Serum immunoglobulin subtypes
Analysis of quantitative Ig levels (including total Ig, IgG, IgG subtypes, IgM, and IgA)
Time frame: 6 months
Influenza infections
Incidence of infections caused by influenza
Time frame: 6 months