Changes of clinical response and bone biochemical markers in patients with ankylosing spondylitis taking etanercept

J Rheumatol. 2007 Aug;34(8):1753-9. Epub 2007 Jun 15.

Abstract

Objective: Tumor necrosis factor-alpha has a prominent role in the inflammatory process and bone resorption in patients with ankylosing spondylitis (AS). We evaluated the markers of clinical efficacy and bone biochemical changes in Korean patients with AS treated with etanercept therapy.

Methods: Serum samples from 26 patients receiving etanercept for refractory AS were obtained at baseline and 12 weeks after treatment. Clinical measures and serum levels of transforming growth factor-Beta (TGF-Beta), matrix metalloproteinase-3 (MMP-3), macrophage-colony stimulating factor (M-CSF), bone-specific alkaline phosphatase (BALP), osteocalcin, C-telopeptide (CTX), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were measured at each timepoint.

Results: Significant improvement of the Bath AS Disease Activity Index (BASDAI) and Functional Index (BASFI) was achieved after 12 weeks (p < 0.001). ASsessments in Ankylosing Spondylitis Working Group (ASAS) 20 criteria were achieved by 22 patients (84.6%) after 12 weeks' treatment. ASAS 50 and 70 were achieved by 10 (38.5%) and 7 patients (26.9%). Serum levels of BALP and osteocalcin were significantly increased after 12 weeks of treatment (p < 0.05). Serum levels of CTX were not changed after treatment. Serum levels of TGF-Beta, MMP-3, and M-CSF were significantly decreased after 12 weeks of treatment (p < 0.05). Serum levels of OPG and RANKL were not changed. Change of MMP-3 had a high correlation coefficient with changes of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) upon etanercept treatment (CRP, r = 0.446, p = 0.022; ESR, r = 0.449, p = 0.021).

Conclusion: In patients with AS, etanercept therapy may be effective for reducing disease activity and improving bone biochemical markers. MMP-3 may be a useful biomarker for monitoring etanercept therapy.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Alkaline Phosphatase / blood
  • Antirheumatic Agents / therapeutic use*
  • Biomarkers / blood
  • Collagen Type I / blood
  • Dose-Response Relationship, Drug
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Korea
  • Macrophage Colony-Stimulating Factor / blood
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Osteocalcin / blood*
  • Osteoprotegerin / blood
  • Peptides / blood
  • RANK Ligand / blood
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Severity of Illness Index
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / physiopathology*
  • Transforming Growth Factor beta / blood

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Collagen Type I
  • Immunoglobulin G
  • Osteoprotegerin
  • Peptides
  • RANK Ligand
  • Receptors, Tumor Necrosis Factor
  • TNFSF11 protein, human
  • Transforming Growth Factor beta
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Macrophage Colony-Stimulating Factor
  • Alkaline Phosphatase
  • Matrix Metalloproteinase 3
  • Etanercept