title: Soluble biomarkers associated with response to treatment with tumor necrosis factor inhibitors in psoriatic arthritis.
abstract: OBJECTIVE
  To identify soluble biomarkers associated with response to therapy with tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA).
  
  
  METHODS
  The study was conducted at a PsA clinic where patients are assessed every 6 months, and serum samples are collected and stored once a year at the time of clinical assessment. Forty patients with active PsA who gave serum samples prior to treatment with TNFi and after at least 3 months of therapy were identified. Patients were classified as TNFi responders if tender joint count was < 3, swollen joint count was 0, and Psoriasis Area and Severity Index score was < 4 at the time the second sample was collected. The following biomarkers were tested by ELISA: TNF superfamily 14, matrix metalloprotease-3 (MMP-3), receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, cartilage oligomeric matrix protein (COMP), CPII, C2C and C1-2C, CS-846, and highly sensitive C-reactive protein. Paired t tests and logistic regression was used for statistical analyses.
  
  
  RESULTS
  After a mean treatment duration of 11 months with TNFi (etanercept 28 patients, adalimumab 6, golimumab 4, infliximab 2), 29 patients were classified as TNFi responders. Baseline level of MMP-3 was independently associated with responder status (OR 1.067 for each 1-unit increase, p = 0.045). A reduction in MMP-3 levels with therapy increased the odds of achieving response (OR 1.213 for each 1-unit change, p = 0.030), whereas a reduction in COMP decreased the odds (OR 0.587, for each 100-unit increase, p = 0.039). None of the other biomarkers was associated with response.
  
  
  CONCLUSIONS
  Baseline as well as reduction in serum MMP-3 and increase in serum COMP are independently associated with response to TNFi therapy in patients with PsA.
authors: Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, Canada.
authors: Vinod
authors: V
authors: Chandran
authors: Hua
authors: H
authors: Shen
authors: Remy A
authors: RA
authors: Pollock
authors: Fawnda J
authors: FJ
authors: Pellett
authors: Adele
authors: A
authors: Carty
authors: Richard J
authors: RJ
authors: Cook
authors: Dafna D
authors: DD
authors: Gladman
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000097:blood* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D064236:Cartilage Oligomeric Matrix Protein / Q000097:blood; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D007074:Immunoglobulin G; D053244:Osteoprotegerin; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab; D000069285:Infliximab; D019278:Matrix Metalloproteinase 3; D000068879:Adalimumab; D000068800:Etanercept
keywords: BIOMARKERS; PSORIASIS; PSORIATIC ARTHRITIS; TREATMENT; TUMOR NECROSIS FACTOR INHIBITORS