title: Effects of subcutaneous and intravenous golimumab on inflammatory biomarkers in patients with rheumatoid arthritis: results of a phase 1, randomized, open-label trial.
abstract: OBJECTIVE
  To evaluate the effects of the anti-TNF-α monoclonal antibody golimumab, administered by s.c. injection or i.v. infusion, on markers of inflammation in patients with RA.
  
  
  METHODS
  In this phase 1, open-label study, patients with active RA were randomized to receive s.c. golimumab 100 mg at baseline and every 4 weeks through week 20 (n = 33; group 1) or i.v. golimumab 2 mg/kg at baseline and week 12 (n = 16; group 2). Serum levels of CRP, IL-6, serum amyloid A (SAA), TNF receptor II (TNFRII), MMP-3, hyaluronic acid, haptoglobin, ferritin and haemoglobin and serum/urine hepcidin were measured at various time points. Associations between the biomarkers were assessed with Spearman's correlations.
  
  
  RESULTS
  In both groups 1 and 2, decreases in mean serum levels of CRP, IL-6, SAA, TNFRII, MMP-3, haptoglobin, ferritin and hepcidin, and mean urine levels of hepcidin occurred within 1 week and were sustained through week 8. Decreases in concentrations of serum CRP, IL-6, SAA, MMP-3, hepcidin, ferritin and haptoglobin and urine hepcidin were maintained through week 24 in group 1, but began to reverse after week 8 in group 2. Among all patients, decreases in serum hepcidin correlated significantly with decreases in serum CRP and ferritin.
  
  
  CONCLUSIONS
  Decreases in serum and urine concentrations of markers of inflammation occurred as early as 24 h after treatment with golimumab, and most of these improvements were sustained through week 24 in group 1.
authors: Janssen Research & Development, LLC, Spring House, PA, USA. doylem@alxn.com
authors: Mittie K
authors: MK
authors: Doyle
authors: Mahboob U
authors: MU
authors: Rahman
authors: Bart
authors: B
authors: Frederick
authors: Charles A
authors: CA
authors: Birbara
authors: Dick
authors: D
authors: de Vries
authors: Gary
authors: G
authors: Toedter
authors: Xiaoying
authors: X
authors: Wu
authors: Dion
authors: D
authors: Chen
authors: Veena K
authors: VK
authors: Ranganath
authors: Mark E
authors: ME
authors: Westerman
authors: Daniel E
authors: DE
authors: Furst
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000652:urine; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D002097:C-Reactive Protein / Q000378:metabolism; D005293:Ferritins / Q000097:blood; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000652:urine; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D064451:Hepcidins; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D005293:Ferritins; C529000:golimumab; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: biological markers; golimumab; hepcidin; pharmacodynamics; rheumatoid arthritis