title: Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis.
abstract: 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.
  
  
  
  We investigated the effect of switching from other DMTs to fingolimod on cerebrospinal fluid (CSF) biomarkers.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lenka
authors.initials: L
authors.lastname: Novakova
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Axelsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Clas
authors.initials: C
authors.lastname: Malmeström
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Lycke
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D000068876:Fingolimod Hydrochloride
keywords: Multiple sclerosis; biomarkers; cerebrospinal fluid; fingolimod; treatment response