Response to 'Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomized study over 21 months'

read with great interest the study by Engvall and colleagues [1] in a recent issue of Arthritis Research & Th erapy. Th e study showed that anti-tumor necrosis factor-alpha (anti-TNF-α) infl iximab therapy is associated with an increase of body fat mass in early rheumatoid arthritis (RA) independently of changes in disease activity and levels of leptin and adiponectin. With respect to this, we have prospectively followed a cohort of patients who had RA refractory to conventional disease-modifying antirheumatic drugs, including metho-trexate, and who, owing to disease severity, underwent anti-TNF-α-infl iximab therapy. Among them, a subgroup of 33 consecutive RA patients who were on periodical treatment with infl iximab and who agreed to participate in the study was assessed to determine the short-term eff ect of this drug on insulin resistance, ghrelin, and adipokine profi le. Besides noting a dramatic improvement of insulin resistance following infl iximab administration [2], we observed that, upon administra tion of this drug, serum ghrelin concentrations (in pico grams per milliliter) increased signifi cantly (896.1 ± 314.8, median 861.2, interquartile range (IQR) 700.5 to 879.9 before infl iximab at time 0 (baseline) and 976.3 ± 373.0, median 905.8, IQR 752.6 to 1,152.8 after infl iximab infusion at 120 minutes; P <0.001) and that increases in ghrelin concentrations were associated with reductions in P-selectin concentrations (r = −0.513; P = 0.002) [3]. How ever, ghrelin concentrations were not related to the DAS28 (disease activity score using 28 joint counts), the mean erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) from disease diagnosis or the ESR, platelet count, CRP, or cumulative prednisone dose at the time of the study [3]. Moreover, we observed a signifi cant correlation between leptin levels and body mass index [4]. Apart from stimulating growth hormone production, ghrelin regulates energy homeostasis through increasing food intake and decreasing fat utilization, leading to increased adiposity through growth hormone-independent mechanisms [5]. Ghrelin is further associated with metabolic syndrome features, and ghrelin administration has benefi cial eff ects not only on cachexia in patients with heart failure and chronic obstructive pulmonary disease but also on insulin sensitivity in overweight patients and endothelial dysfunction in patients with metabolic syndrome [6]. Additionally, ghrelin has potent anti-infl ammatory eff ects, including the inhibition of proinfl ammatory cytokine production by T lymphocytes and monocytes within the immune system and human endothelial cells [7]. Besides noting the rapid decrease of P-selectin, a …