TY - JOUR

T1 - Clinical remission following treatment with tumour necrosis factor-alpha antagonists is not accompanied by changes in asymmetric dimethylarginine in patients with rheumatoid arthritis

AU - Sandoo, Aamer

AU - Dimitroulas, Theodoros

AU - Toms, Tracey E

AU - Hodson, James

AU - Veldhuijzen van Zanten, Jet J C S

AU - Smith, Jacqueline P

AU - Kitas, George D

N1 - Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

PY - 2012/11

Y1 - 2012/11

N2 - OBJECTIVES: Rheumatoid arthritis (RA) is characterised by impaired endothelial function which contributes to increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and contributes to endothelial dysfunction. The aim of the present longitudinal study was to investigate the effects of tumour necrosis factor alpha (TNFα) antagonists on serum concentrations of ADMA in RA patients.DESIGN AND METHODS: Thirty-five patients (age (mean ± SD) 55 ± 15 years, 21 women) who qualified for anti-TNFα therapy were included in the study. ADMA was measured by ELISA in all patients prior to starting anti-tumour necrosis factor alpha treatment, and 2 weeks and 3 months after initiation of treatment. Generalised estimating equations were used to analyse the change in a range of factors after the treatment commenced, and to test the relationship between ADMA and various inflammatory parameters.RESULTS: Anti-tumour necrosis factor alpha therapy significantly reduced ESR, CRP, fibrinogen and disease activity score 28 (all p<0.001). ADMA levels did not change significantly following 2 weeks or 3 months treatment using three different tumour necrosis factor alpha inhibitors, despite the fact that CRP (p=0.016), and DAS28 (p=0.025) were found to be significantly associated with ADMA levels after treatment with TNFα antagonists.CONCLUSION: ADMA levels do not change significantly during anti-TNF therapy, despite the fact that they associate with CRP and DAS28, which are significantly reduced during such treatment in patients with rheumatoid arthritis. Levels of inflammation after treatment with TNFα antagonists are significantly associated with ADMA levels in patients with rheumatoid arthritis.

AB - OBJECTIVES: Rheumatoid arthritis (RA) is characterised by impaired endothelial function which contributes to increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and contributes to endothelial dysfunction. The aim of the present longitudinal study was to investigate the effects of tumour necrosis factor alpha (TNFα) antagonists on serum concentrations of ADMA in RA patients.DESIGN AND METHODS: Thirty-five patients (age (mean ± SD) 55 ± 15 years, 21 women) who qualified for anti-TNFα therapy were included in the study. ADMA was measured by ELISA in all patients prior to starting anti-tumour necrosis factor alpha treatment, and 2 weeks and 3 months after initiation of treatment. Generalised estimating equations were used to analyse the change in a range of factors after the treatment commenced, and to test the relationship between ADMA and various inflammatory parameters.RESULTS: Anti-tumour necrosis factor alpha therapy significantly reduced ESR, CRP, fibrinogen and disease activity score 28 (all p<0.001). ADMA levels did not change significantly following 2 weeks or 3 months treatment using three different tumour necrosis factor alpha inhibitors, despite the fact that CRP (p=0.016), and DAS28 (p=0.025) were found to be significantly associated with ADMA levels after treatment with TNFα antagonists.CONCLUSION: ADMA levels do not change significantly during anti-TNF therapy, despite the fact that they associate with CRP and DAS28, which are significantly reduced during such treatment in patients with rheumatoid arthritis. Levels of inflammation after treatment with TNFα antagonists are significantly associated with ADMA levels in patients with rheumatoid arthritis.

KW - Adult

KW - Aged

KW - Antirheumatic Agents

KW - Arginine

KW - Arthritis, Rheumatoid

KW - Biomarkers

KW - Female

KW - Humans

KW - Longitudinal Studies

KW - Male

KW - Methotrexate

KW - Middle Aged

KW - Remission Induction

KW - Sulfasalazine

KW - Treatment Outcome

KW - Tumor Necrosis Factor-alpha

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.clinbiochem.2012.07.092

DO - 10.1016/j.clinbiochem.2012.07.092

M3 - Article

C2 - 22820438

VL - 45

SP - 1399

EP - 1403

JO - Clinical Biochemistry

JF - Clinical Biochemistry

SN - 0009-9120

IS - 16-17

ER -