PT  - JOURNAL ARTICLE
AU  - Fissolo, Nicolás
AU  - Pappolla, Agustin
AU  - Rio, Jordi
AU  - Villar, Luisa M.
AU  - Perez-Hoyos, Santiago
AU  - Sanchez, Alex
AU  - Gutierrez, Lucía
AU  - Montalban, Xavier
AU  - Comabella, Manuel
TI  - Serum Levels of CXCL13 Are Associated With Teriflunomide Response in Patients With Multiple Sclerosis
AID  - 10.1212/NXI.0000000000200050
DP  - 2023 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e200050
VI  - 10
IP  - 1
4099  - http://nn.neurology.org/content/10/1/e200050.short
4100  - http://nn.neurology.org/content/10/1/e200050.full
SO  - Neurol Neuroimmunol Neuroinflamm2023 Jan 01; 10
AB  - Background and Objectives To identify biomarkers associated with treatment response in patients with multiple sclerosis (MS) treated with the oral therapies teriflunomide, dimethyl fumarate (DMF), and fingolimod.Methods Serum levels of IL-6, IL-17, TNF-α, granulocyte-macrophage colony-stimulating factor, IL-10, interferon-gamma (IFN-γ) IL-1β, and chemokine ligand 13 (CXCL13) were measured at baseline and 12 months with single molecule array (Simoa) assays in a cohort of patients with MS treated with teriflunomide (N = 19), DMF (N = 22), and fingolimod (N = 25) and classified into “no evidence of disease activity” (NEDA) and EDA patients after 1 year of treatment.Results Serum CXCL13 and TNF-α levels were significantly decreased after treatment with teriflunomide in NEDA compared with EDA patients after 1 year of treatment (p = 0.008 for both cytokines). These findings were validated in an independent cohort of patients with MS treated with teriflunomide (N = 36) and serum CXCL13, and TNF-α levels were again significantly reduced in NEDA patients (p < 0.0001 for CXCL13 and p = 0.003 for TNF-α). CXCL13, but not TNF-α, showed good performance to classify NEDA and EDA patients according to a cut-off value of 9.64 pg/mL based on the change in CXCL13 levels between baseline and 12 months, with a sensitivity of 75% and specificity of 82% in the original cohort, and sensitivity of 65.4% and specificity of 60% in the validation cohort.Discussion Altogether, these results point to CXCL13 as a treatment response biomarker to teriflunomide in relapsing-remitting patients with MS, and the change in CXCL13 levels during the first year of treatment can be used in clinical practice to identify optimal responders to teriflunomide.AUC=area under the ROC curve; CXCL13=chemokine ligand 13; DMF=dimethyl fumarate; EDA=evidence of disease activity; EDSS=Expanded Disability Status Scale; GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN-γ=interferon-gamma; MS=multiple sclerosis; NEDA=no evidence of disease activity; ROC=Receiver operating characteristic; RRMS=relapsing-remitting MS