Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis

J Neuroimmunol. 2016 Nov 15:300:59-65. doi: 10.1016/j.jneuroim.2016.06.005. Epub 2016 Jul 2.

Abstract

A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3months, the change in IL-4 from baseline to 6months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets.

Keywords: Biomarkers; Cytokines; Glatiramer acetate; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cytokines / antagonists & inhibitors
  • Cytokines / blood*
  • Female
  • Follow-Up Studies
  • Glatiramer Acetate / pharmacology
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Predictive Value of Tests
  • Prospective Studies
  • Treatment Outcome

Substances

  • Biomarkers
  • Cytokines
  • Immunosuppressive Agents
  • Glatiramer Acetate