Session Type: Abstract Submissions (ACR)
Background/Purpose: TNF-inhibitors are known to decrease cardiovascular events in rheumatoid arthritis (RA) as compared with synthetic disease modifying anti-rheumatic drugs (sDMARD). However, mechanisms involved remain to be explored. Osteoprotegerin (OPG) is increased and independently associated with coronary-artery atherosclerosis in patients with RA. Adiponectine has cardioprotective functions and joint-destruction role in RA. Oxidative stress, especially urinary F(2) isoprostanes, predicts cardiovascular mortality and is increased in RA. We aimed to explore metabolic parameters changes after 6 months of anti-TNF therapy or sDMARD in patients with RA.
Methods: Twenty-four patients were included in the etanercept (ETN) group and 17 in the sDMARD group. Metabolic parameters were evaluated at baseline and at 6 months. HOMA was calculated as (insulin*glycemia)/22.5. Urinary F(2) isoprostanes were assessed using negative ion chemical ionization gas chromatography-mass spectrometry. OPG and total adiponectine levels were determined by enzyme linked immunosorbent assay. Changes were evaluated using paired-t-tests or Wilcoxon matched-pairs signed rank tests and correlations using spearman tests.
Results: Patients of the ETN group had a significantly longer RA duration, were more often RF and ACPA positive and had more often erosions and steroids. Patients had similar blood pressure, body mass index (BMI), glycemic and lipid parameters, homocystein, OPG and isoprostanes at baseline in both groups. Adiponectine tended to be higher in ETN group (196 [126-228] vs 136 [196-286] µg/ml, p=0.08).
Isoprostanes at baseline correlated with triglycerides (r=0.42, p<0.05) and inversely correlated with HDL (r=-0.37, p<0.05), HbA1c (r=-0.38, p<0.05).OPG at baseline correlated with age (r=0.48, p<0.01), DAS28 (r=0.38, p<0.05), CRP (r=0.53, p<0.01), HbA1c (r=0.51, p<0.01).
A significant decrease of BMI at 6 months was observed in the ETN group (-0.6 ± 1.4 kg/m², p<0.05 and 1.8 ± 0.62 kg/m² in ETN and sDMARD group respectively). The BMI variation was significantly different between the 2 groups (p=0.02). No correlation was found between BMI change and steroid changes. No change in mean blood pressure, HOMA, HbA1c, cholesterol and homocystein was observed after 6 months of either treatment. A significant decrease of OPG (-0.93 ± 1.64 pmol/l, p=0.03 vs 0.35 ±2.05 pmol/l, NS; respectively in ETN and sDMARD groups), isoprostanes (-227 ± 243 pmol/mmol of urinary creatinine, p=0.01 vs -18± 141, NS) and a tendancy to adiponectine increase (62 ± 217 µg/ml, p=0.08 vs -13 ±67 µg/ml, NS) was found in patients treated with ETN at 6 months whereas no change was observed in the sDMARD group. Variations were different between the 2 groups for isoprostanes (p<0.05), with a tendancy for OPG (p=0.06) and adiponectine (p=0.09). Isoprostanes and OPG changes were not correlated with DAS28 or CRP variations between baseline and 6 months.
Conclusion: ETN induced a decrease of oxidative stress and OPG which may partially explain the protective cardiovascular effect of TNF inhibitors.
C. I. Daien,
A. M. Dupuy Gorce,
J. P. Cristol,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/etanercept-induces-a-significant-decrease-of-oxidative-stress-and-osteoprotegerin-compared-with-sdmard-in-patients-with-rheumatoid-arthritis/