Effects of subcutaneous and intravenous golimumab on inflammatory biomarkers in patients with rheumatoid arthritis: results of a phase 1, randomized, open-label trial

Rheumatology (Oxford). 2013 Jul;52(7):1214-9. doi: 10.1093/rheumatology/kes381. Epub 2013 Feb 14.

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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01362153.

Keywords: biological markers; golimumab; hepcidin; pharmacodynamics; rheumatoid arthritis.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antimicrobial Cationic Peptides / blood
  • Antimicrobial Cationic Peptides / urine
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / urine
  • Biomarkers / blood*
  • Biomarkers / urine*
  • C-Reactive Protein / metabolism
  • Ferritins / blood
  • Hepcidins
  • Humans
  • Inflammation / blood
  • Inflammation / drug therapy
  • Inflammation / urine
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Interleukin-6 / blood
  • Matrix Metalloproteinase 3 / blood
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antimicrobial Cationic Peptides
  • Biomarkers
  • HAMP protein, human
  • Hepcidins
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Ferritins
  • golimumab
  • MMP3 protein, human
  • Matrix Metalloproteinase 3

Associated data

  • ClinicalTrials.gov/NCT01362153