One major medical issue with regards to the overall rheumatoid arthritis(RA) related inflammation and RA- cardiovascular risk (CVR) is the presence of the metabolic syndrome which is thought to be a state of chronic inflammation. We will focus on : . Prevalence of the metabolic syndrome (MetS) in RA and of its principal components on the inflammatory status of RA.. Influence of the MetS and of its componenets on the outcome of RA under conventional treatments and under biologics therapy.. Gene expression in adipocytes vs house keeping gene . Perspectives for a better therapeutic approach.
We analyzed three cohorts of patients (564 RA (346 early RA-ERA patients, 218 long standing RA-LSRA with severe disease requiring biologic treatment), 452 SLE patients and 296 SSc patients. The Metabolic syndrome was defined according to the American Heart Association/Updated NCEP criteria (1). BMI was categorized into 3 classes, i.e <25 kg/m2 (normal weight), 25-30 kg/m2 (overweight), and >30 kg/m2 (obese). Gene expression profile was looked for in fat adipocytes in culture after four passages and after stimulation.
The prevalence of MetS in the ERA cohort was 25.3%; and 12.5 % were obese. In LSRA the MetS was present in 27% and 12.8% were obese; in SLE patients MetS was observed in 31.3%. and 10% were obese. In the SSc MetS was observed in 14.2% and the prevalence of obesity was 10.4%. At baseline in ERA patients ESR and CRP, but not DAS, were significantly higher than in MetS negative patients. When following longitudinally ERA patients, all treated aiming at remission, we observed that MetS at baseline did not change the major outcome (CDAI or DAS remission); BMI did influence the major outcome: overweight and obese patients reached a lower rate of remission, with DAS and CDAI criteria, at 6 and 12 month follow-up visits (sustained DAS remission at 12th month: 49.1% in normal, 28.7% in overweight, 34.1% in obese, p=0.008; CDAI remission at 12th month: 50%, 37.1%, 31% in normal, overweight and obese, respectively, p=0.07). An higher percentage of obese and overweight ERA patients were under anti-TNF treatment after 12 months of follow-up (28.1% of obese, 28.8% of overweight, 16.2% of normal weight). The independent variables associated with the probability of being in anti-TNF therapy at 12th month follow-up were : age <55 years (OR: 2.7 (1.4-5.3)), baseline DAS≥3.7 (OR: 2.27 (1.19-4.34) and BMI≥25 (OR: 2.36 (1.21-4.59)). In LSRA patients with MetS at baseline had a lower chance of achieving both a Good EULAR response at 12 months (26.1 % vs 50 %, p =0.001) and a DAS remission (20.3 vs 32.4 %, p =0.06). In LSRA the independent predictors of “not obtaining Good Response at the 12th month of anti-TNF therapy” were the presence of hyperglicemia (OR (95%CI): 2.78 (1.06-7.14)), and hypertension (OR (95%CI): 3.03 (1.51-5.88)) in addition to an HAQ>1.5 (OR (95%CI): 2.22 (1.01-4.55)) at baseline.
TNF, IL6, IL1, BAFF, BAFF-R and FcR genes were all expressed in adipocytes, and more particularly the PEDF gene was at least 3 fold higher in obese fat biopsies.
Data show that MetS is present in a quarter of all RA either early or LSRA. In early RA it does not seem to influence the outcome, yet one of its component, i.e. obesity plays a negative role in the achievement of a major outcome. In LSRA MetS influences the achievement of both DAS remission and Good EULAR response. Obesity plays a crucial role in negatively influencing the outcome in ERA. Gene expression analysis has shown that a biomarker of obesity, namely PEDF, which exerts anti-inflammatory and anti-angiogenic effects, appears to be a possible biomarker for assessing a therapeutic intervention. Certainly the data at hand suggest that obesity and MetS should become usual targets for therapy in the RA population along with the targeted therapy strategies aiming at remission to avoid the overall CV risk
Alberti KGGM, et al. Circulation. 2009;120:1640-1645
Disclosure of Interest G. Ferraccioli Grant/research support from: Pfizer, Roche