Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis. (January 2017)

• Record Type: Journal Article
• Authors: Novakova, Lenka; Axelsson, Markus; Khademi, Mohsen; Zetterberg, Henrik; Blennow, Kaj; Malmeström, Clas; Piehl, Fredrik; Olsson, Tomas; Lycke, Jan
• Is Part Of: Multiple sclerosis. Volume 23:Number 1(2017)
• Page Start: 62
• Page End: 71
• Publication Date: 2017-01
• Subjects: Multiple sclerosis -- biomarkers -- cerebrospinal fluid -- fingolimod -- treatment response; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458516639384
• Languages: English
• ISSNs: 1352-4585

Abstract

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.