Disparate effects of anti-TNF-α therapies on measures of disease activity and mediators of endothelial damage in ankylosing spondylitis

Pharmacol Rep. 2013;65(4):891-7. doi: 10.1016/s1734-1140(13)71070-3.

Abstract

Background: Asymmetric dimethylarginine (ADMA) is associated with endothelial injury. Increased ADMA levels are found in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We set out to assess the ADMA and symmetric dimethylarginine (SDMA) levels in AS, RA, and healthy controls, and in the anti-TNF treated patients with active AS.

Methods: In 78AS patients and 29 RA patients who were anti-TNF treatment naive at baseline, along with 23 healthy control subjects, we assessed erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), ADMA, and SDMA. For AS patients, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain VAS and patient's global activity of disease were calculated. After 6 months, we repeated the assessment in 30 out of the 78 AS patients in whom the anti-TNF treatment was initiated.

Results: The baseline mean (SD) plasma ADMA concentration of AS patients was 0.64 (0.19) μmol/l and did not differ from controls (0.65 [0.19] μmol/l, p > 0.05). In the RA group, ADMA concentration was higher than in controls (0.77 vs. 0.65 μmol/l, p < 0.05). Both at baseline and at follow-up, ADMA levels correlated positively with BASDAI (R = 0.52, p = 0.02, and R = 0.47, p = 0.04, baseline and follow-up, respectively). Six months of anti-TNF treatment did not influence ADMA concentration (0.51 [0.12] vs. 0.51 [0.11] μmol/l, p = 0.70).

Conclusion: An absence of changes in plasma ADMA levels in the anti-TNF treated AS group despite the improvement in disease activity (BASDAI) and inflammation (ESR, CRP) may suggest either a lack of effect, or, even if such an effect were to take place, it needs not imply measurable changes in blood ADMA.

Publication types

  • Controlled Clinical Trial
  • Multicenter Study

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / therapeutic use
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy
  • Blood Sedimentation / drug effects
  • C-Reactive Protein / metabolism
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Male
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Severity of Illness Index
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / drug therapy*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • N,N-dimethylarginine
  • C-Reactive Protein
  • Arginine
  • Adalimumab
  • Etanercept