The CXCL13 index biomarker predicts success or failure of moderate-efficacy disease-modifying therapies in multiple
Andrew R Pachner1, Steven C Pike2, Andrew D Smith1
1Department of Neurology, Dartmouth Hitchcock Medical Center, One Medical Center Road, Lebanon, NH 03756, USA.
Background And Objectives:
Currently there are no biomarkers that can reliably guide clinicians at the onset of MS, choosing between low-risk moderate efficacy disease-modifying therapies(ME-DMTs) and stronger, but higher-risk high-efficacy disease-modifying therapies(HE-DMTs) . The objective of this work was to analyze whether the CXCL13 index (ICXCL13), a measure of intrathecal synthesis of CXCL13, can predict whether ME-DMTs will be a success or failure in controlling MS activity in a real-world study.
Methods:
109 patients with MS at Dartmouth-Hitchcock Medical Center who underwent a lumbar puncture were followed clinically for a minimum of two years. Cerebrospinal fluid(CSF) and serum were banked, tested for CXCL13 concentrations by Luminex and ELISA, and ICXCL13 calculated.
Results:
Patients with clinically isolated syndrome (CIS) were divided into those with a low or high ICXCL13.(LOCIS or HI-CIS). A low ICXCL13 predicted that ME-DMT or no DMT would be successful in achieving NEDA(no evidence of disease activity), while a high ICXCL13 predicted failure of ME-DMTs to achieve NEDA. The ICXCL13 outperformed other potential predictive biomarkers in CIS.
Discussion:
CIS represents a "window of opportunity" for optimal treatment with DMTs, but the optimal strategy is controversial, and what is urgently needed is a biomarker with a high negative and positive predictive value. The data from this study indicates that patients with CIS do well with ME-DMTs or no DMTs if the ICXCL13 is low, but fail treatment with ME-DMTs if the ICXCL13 is high.
