期刊
MULTIPLE SCLEROSIS JOURNAL
卷 23, 期 1, 页码 62-71出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458516639384
关键词
Multiple sclerosis; biomarkers; cerebrospinal fluid; fingolimod; treatment response
资金
- Swedish Federal Government (LUA/ALF agreement)
- Swedish Society of the Neurologically Disabled
- Research Foundation of the Multiple Sclerosis Society of Gothenburg
- Edit Jacobson Foundation
- AFA foundation
- Swedish medical research council
- Knut and Alice Wallenberg foundation
- Novartis
- Biogen
Background: The disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) vary in their mode of action and when therapies are changed, the consequences on inflammatory and degenerative processes are largely unknown. Objective: We investigated the effect of switching from other DMTs to fingolimod on cerebrospinal fluid (CSF) biomarkers. Methods: 43 RRMS patients were followed up after 4-12 months of fingolimod treatment. Concentrations of C-X-C motif chemokine 13 (CXCL13), chemokine (C-C motif) ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), neurofilament light protein (NFL), and neurogranin (NGRN) were analyzed by enzyme-linked immunosorbent assay (ELISA), while chitotriosidase (CHIT1) was analyzed by spectrofluorometry. Results: The levels of NFL, CXCL13, and CHI3L1 decreased (p < 0.05) after fingolimod treatment. Subgroup analysis revealed a reduction in NFL (p < 0.001), CXCL13 (p = 0.001), CHI3L1 (p < 0.001), and CHIT1 (p = 0.002) in patients previously treated with first-line therapies. In contrast, the levels of all analyzed biomarkers were essentially unchanged in patients switching from natalizumab. Conclusion: We found reduced inflammatory activity (CXCL13, CHI3L1, and CHIT1) and reduced axonal damage (NFL) in patients switching from first-line DMTs to fingolimod. Biomarker levels in patients switching from natalizumab indicate similar effects on inflammatory and degenerative processes. The CSF biomarkers provide an additional measure of treatment efficacy.
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