Serum Levels of CXCL13 Are Associated With Teriflunomide Response in Patients With Multiple Sclerosis. Issue 1 (21st January 2023)

• Record Type: Journal Article
• Authors: Fissolo, Nicolás; Pappolla, Agustin; Rio, Jordi; Villar, Luisa M.; Perez-Hoyos, Santiago; Sanchez, Alex; Gutierrez, Lucía; Montalban, Xavier; Comabella, Manuel
• Is Part Of: Neurology. Volume 10:Issue 1(2023)
• Publication Date: 2023-01-21
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000200050
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : 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.