title: Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis.
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.
authors.affiliation: Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States. Electronic address: valenzru@gmail.com.
authors.forename: R M
authors.initials: RM
authors.lastname: Valenzuela
authors.affiliation: Carolina Medical Center, Multiple Sclerosis Center, Charlotte, North Carolina, 28207, United States. Electronic address: gpmonk1@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Kaufman
authors.affiliation: Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States. Electronic address: kbalashov@yahoo.com.
authors.forename: K E
authors.initials: KE
authors.lastname: Balashov
authors.affiliation: Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States. Electronic address: itoko@rwjms.rutgers.edu.
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.affiliation: Rutgers University, Department of Statistics and Biostatistics, Piscataway, NJ 08854, United States. Electronic address: buyske@stat.rutgers.edu.
authors.forename: S
authors.initials: S
authors.lastname: Buyske
authors.affiliation: Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States. Electronic address: jalbutsu@rutgers.edu.
authors.forename: S
authors.initials: S
authors.lastname: Dhib-Jalbut
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate
keywords: Biomarkers; Cytokines; Glatiramer acetate; Multiple sclerosis