Journal
CLINICAL IMMUNOLOGY
Volume 176, Issue -, Pages 87-93Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2017.01.001
Keywords
Biomarkers; Natalizumab; Fingolimod; Multiple sclerosis; Treatment change; Flow cytometry
Categories
Funding
- Genmab
- UCB Pharma
- Biogen-Idec
- Novartis
- Red Bull
- Merck
- European Union
- FWF Osterreichischer Fond zur Wissenschaftsforderung
- Bundesministerium fur Wissenschaft und Forschung
- Almirall
- Bayer
- Genzyme
- Medtronic
- Merck-Serono
- Roche
- Sanofi-Aventis
- TEVA ratiopharm
- Biogen-ldec
- Merck Serono
- Teva
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Natalizumab (NZB) discontinuation during a treatment change is associated with recurrence of disease activity in a significant proportion of multiple sclerosis (MS) patients. The immunological basis why disease reactivation occurs in selected patients is unresolved. In search of a prognostic biomarker for a safe and effective transition from NZB to fingolimod, we monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two drugs in 12 MS patients until six months on fingolimod. Clearance of free and cell-bound NZB, re-expression of alpha-4, and fingolimod-mediated changes on CD8+ and CD4+ T cell subsets showed pronounced interindividual variability. Higher frequencies of memory CD8+ T cells after six months on fingolimod were the sole association with disease reactivation. None of the investigated parameters thus had potential as prognostic biomarker for the outcome of the switch. Our findings rather support the thesis of broad interindividual differences in the immunopathogenesis of MS. (C) 2017 Elsevier Inc. All rights reserved.
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