Background Rheumatoid artritis (RA) is characterized by increased cardiovascular (CV) mortality and by a metabolic profile including obesity, cachexia, insulin resistance, dyslipidaemia. Traditional DMARDs as well as biologics decreases inflammation and could thus improve CV risk. However, the effects of such therapies on lipids and body composition are still unclear.
Objectives To investigate the effects of tocilizumab, an inhibitor of the IL6 pathway on markers of subclinical atherosclerosis and body composition in active RA.
Methods We conducted an open 1-year follow-up study of patients with active RA treated with tocilizumab. Waist circumference (WC), body mass index (BMI), total and regional body fat and lean mass assessed with dual-energy x-ray absorptiometry, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (TG), fasting glucose, blood pressure, and arterial stiffness (pulse wave velocity PWV, augmentation index AIx) were measured at baseline when started first treatment with tocilizumab, 6 months and 1 year of treatment. The longitudinal data were explored in univariate analysis using a random-effects model. To assess the issue of missing data, the estimation methods developed by Verbeke and Molenberg were considered in this study.
Results 21 RA patients, including 16 women with a mean age of 57.8±10.5 years were included. RA duration was 8.5 years [IQR 1.7–21.5]. 14 had positive rheumatoid factors, 17 anti-CCP antibodies, 13 were erosive. At baseline, 19 patients received a DMARD, 14 steroids, 11 cholesterol-lowering drug therapy, 1 anti-diabetic drug, 6 antihypertensive medication. 18 patients have previously received at least one biologic. The mean DAS 28 at baseline was 4.7±1 and decreased significantly at 6 and 12 months (2.92±0.8 and 2.8±1.5 respectively, p<0.001). No changes for WC, blood pressure, fasting glucose, TG were observed. LDL cholesterol significantly decreased at 12 months (1.26±0.32 g/l vs 1.01±0.4 g/l, p=0.04) and atherogenic index did not change. Arterial stiffness (PWV, AIx) was not modified after 6 or 12 months of treatment with tocilizumab. Significant weight gain (61.7±19.3 vs 63.7±16.1 kg p=0.005) and BMI (23.6±6.7 vs 24.8±6, p<0.001) were observed at 1 year. Fat mass, fat mass index, appendicular fat did not change at 6 and 12 months. In contrast, lean mass (42.1±11.1 vs 43.2±11.3 kg, p=0.01) and fat free mass index (16.7±3 vs 17.4±3.02, p=0.01) increased at 1 year with decrease of trunk/peripheral fat ratio (0.77±0.2 vs 0.7±0.17 p<0.001). There was a significant gain in appendicular lean mass (17.7±5.4 vs 18±5.3 and 18.7±5.6 kg, p=0.04 and p<0.001 respectively) and skeletal muscle mass index (6.7±1.4 vs 6.9±1.4 and 7.2±1.5, p=0.03 and p<0.001 respectively) at 6 and 12 months with a significant change between 6 and 12 months (p=0.017).
Conclusions Despite weight gain during efficacious treatment with IL6 inhibitor, no increase in fat, metabolic syndrome or CV risk markers have been observed. In contrast, muscle gain with increase of lean mass was detected at 1 year suggesting that blocking IL6 might be efficient in rheumatoid cachexia and sarcopenia.
Acknowledgements This work was supported by a grant from Chugai and Roche
Disclosure of Interest None declared