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Purpose: To evaluate the long-term consequences of TNFα inhibitors on body composition and fat distribution, as well as changes in serum adipokines in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Methods: Eight patients with RA and twelve with AS requiring a TNFα inhibitor were prospectively followed for 2 years. Body composition was evaluated by dual X-ray absorptiometry and included measurements of total fat mass, lean mass, fat in the gynoid and android regions, and visceral fat. Serum leptin, total and high molecular weight (HMW) adiponectin, resistin, and ghrelin were also assessed. Results: There was a significant gain in body mass index ( p = 0.05) and a tendency for weight ( p = 0.07), android fat ( p = 0.07), and visceral fat ( p = 0.059) increase in patients with RA, while in AS, total fat mass significantly increased ( p = 0.02) with a parallel weight gain ( p = 0.07). When examining the whole population of patients, we observed after 2 years a significant increase in body weight (+1.9 %; p = 0.003), body mass index (+2.5 %; p = 0.004), total fat mass (+11.1 %; p = 0.007), and fat in the android region (+18.3 %; p = 0.02). There was a substantial, albeit nonsignificant gain in visceral fat (+24.3 %; p = 0.088). Lean mass and gynoid fat were not modified. No major changes were observed for serum leptin, total adiponectin, and ghrelin, while HMW adiponectin and the HMW/total adiponectin ratio tended to decrease (−15.2 %, p = 0.057 and −9.3 %, p = 0.067, respectively). Resistin decreased significantly (−22.4 %, p = 0.01). Conclusions: Long-term TNFα inhibition in RA and AS is associated with a significant gain in fat mass, with a shift to the android (visceral) region. This fat redistribution raises questions about its influence on the cardiovascular profile of patients receiving these treatments. [ABSTRACT FROM AUTHOR]