1.
Rheumatoid arthritis and metabolic syndrome.
Kerekes, G, Nurmohamed, MT, González-Gay, MA, Seres, I, Paragh, G, Kardos, Z, Baráth, Z, Tamási, L, Soltész, P, Szekanecz, Z
Nature reviews. Rheumatology. 2014;(11):691-6
Abstract
Rheumatoid arthritis (RA), especially active disease, is associated with considerable changes in body composition, lipids, adipokines and insulin sensitivity. Metabolic changes, such as increased total cholesterol, LDL cholesterol and triglyceride levels, occur even in preclinical RA. Active RA is associated with decreased lipid levels, BMI, fat and muscle mass, as well as altered lipid profiles. Some of these changes are also seen in metabolic syndrome, and could increase cardiovascular mortality. Importantly, the systemic inflammation underlying RA is an independent risk factor for cardiovascular disease. This Perspectives article summarizes data on the associations of various components of metabolic syndrome with RA, and discusses the effects of biologic therapy on these factors. The authors propose that components of metabolic syndrome should be monitored in patients with RA throughout the disease course, and argue that optimal disease control using biologic agents might attenuate several adverse effects of metabolic syndrome in these patients.
2.
Predictors of early minimal disease activity in patients with psoriatic arthritis treated with tumor necrosis factor-α blockers.
Iervolino, S, Di Minno, MN, Peluso, R, Lofrano, M, Russolillo, A, Di Minno, G, Scarpa, R
The Journal of rheumatology. 2012;(3):568-73
Abstract
OBJECTIVE To identify predictors of early minimal disease activity in patients with psoriatic arthritis (PsA) receiving tumor necrosis factor-α (TNF-α) antagonists. METHODS In total 146 consecutive patients with PsA eligible for anti-TNF-α therapy were enrolled. At baseline (T0) information about age, sex, PsA subset, disease duration, comorbidities, and treatments was collected. All subjects were tested for metabolic syndrome (MetS) and/or liver steatosis. A clinical and laboratory evaluation was performed at T0 and at 3 months (T3). Changes in all these variables were compared in subjects achieving minimal disease activity (MDA) and those who did not. RESULTS Among 146 PsA subjects, 10 discontinued therapy before 3-month followup because of adverse events; thus 136 concluded the study. All clinical outcome measures changed significantly from T0 to T3. Erythrocyte sedimentation rate showed a significant reduction (p < 0.001). C-reactive protein (CRP), serum cholesterol, and triglycerides showed no significant variation (p > 0.05). The prevalence of MetS and liver steatosis showed no significant differences between subjects achieving MDA and those who did not (p = 0.347 and 0.053, respectively). Patients achieving MDA at T3 were younger than those not achieving MDA (p = 0.001). A lower baseline tender joint count (p = 0.001), swollen joint count (p = 0.013), Bath Ankylosing Spondylitis Disease Activity Index (p = 0.021), and Ritchie index (p = 0.006) were found in subjects achieving MDA. Age (OR 0.896, p = 0.003) and Bath Ankylosing Spondylitis Functional Index (BASFI) (OR 0.479, p = 0.007) inversely predicted, whereas CRP (OR 1.78, p = 0.018) directly predicted, achievement of MDA at T3. CONCLUSION In patients with PsA, age, CRP, and BASFI at the beginning of treatment were found to be reliable predictors of MDA after 3 months of TNF-α blocker therapy.
3.
Short-term effect of anti-TNF-alpha therapy on nitric oxide production in patients with severe rheumatoid arthritis.
Gonzalez-Gay, MA, Garcia-Unzueta, MT, Berja, A, Vazquez-Rodriguez, TR, Miranda-Filloy, JA, Gonzalez-Juanatey, C, de Matias, JM, Martin, J, Dessein, PH, Llorca, J
Clinical and experimental rheumatology. 2009;(3):452-8
Abstract
OBJECTIVE TNF-alpha increases expression of inducible nitric oxide synthase (iNOS) in macrophages and vascular endothelial cells. Under normal conditions, iNOS activity is very low. However, iNOS activity is stimulated during inflammation by cytokines such as TNF-alpha and the amount of NO produced by iNOS may be a 1,000-fold greater than that produced by endothelial NOS. Since functional iNOS gene polymorphisms have been associated with susceptibility to rheumatoid arthritis (RA), drugs blocking TNF-alpha might decrease production of cytotoxic concentrations of NO leading to beneficial effect on RA or its complications. In the present study we investigated whether the infusion of the anti-TNF-alpha-infliximab may yield a short-term effect altering circulating NO oxidation products in patients with severe RA. METHODS We investigated 33 RA patients on periodical treatment with infliximab. Serum levels of nitrates, nitrites and NOx (nitrites+nitrates) were determined immediately prior to and after infliximab infusion. Correlation with clinical variables, laboratory markers of inflammation, metabolic syndrome features, adipokines and adhesion molecules was also assessed. RESULTS Upon infliximab administration, serum NOx concentrations (microM) decreased significantly ([mean+/-SD: 15.0+/-8.8; median: 11.9; interquartile range: 9.2-18.5] before infliximab-time 0 (baseline) and [12.9+/-6.3; 10.9; 7.8-17.2] after infliximab infusion-time 120 minutes; p=0.03). It was also the case for nitrates (9.8+/- 8.3; 7.6; 5.5-10.2] before infliximab and [7.5+/-4.0; 6.6; 5.2-10.0] after infliximab infusion; p=0.008). There was a positive correlation between basal levels of nitrites and leptin concentration prior to infliximab administration. However, no significant correlations between NO oxidation products and clinical or other laboratory variables were found. CONCLUSIONS Our results show, for the first time, a short-term effect of anti-TNF-alpha therapy on the levels of nitric oxide production.