Background/Purpose:

Rheumatoid arthritis (RA) is characterized by increased cardiovascular risk and metabolic changes including cachectic obesity, insulin resistance, dyslipidemia. DMARDs decrease inflammation and could thus improve cardiovascular risk but their effects on body composition and metabolic profile remain unclear. We investigated the effects of tocilizumab, an inhibitor of the IL6 pathway on body composition and metabolic profile in active RA.

Methods: We conducted an open 1-year follow-up study of 21 patients with active RA treated with tocilizumab. Waist circumference (WC), body mass index (BMI), body composition (dual-energy x-ray absorptiometry), lipid profile, fasting glucose, blood pressure, and arterial stiffness were measured at baseline when started tocilizumab, 6 months and 1 year of treatment. At baseline, RA patients were compared with 21 controls matched for age, sex, BMI and metabolic syndrome. The longitudinal data were explored using a random-effect models. To assess the issue of missing data, the estimation methods developed by Verbeke and Molenberghs 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]. At baseline, 19 patients received a DMARD, 14 steroids, 11 cholesterol-lowering drug, 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). Compared to controls, RA patients had significantly lower total (42.1±11.1 vs 47.5±8.7, p=0.02) and appendicular lean mass (17.7±5.4 vs 20.1±3.9, p=0.03). During treatment with tocilizumab, no changes for WC, blood pressure, fasting glucose, lipid profile or arterial stiffness were observed. Significant weight gain (61.8±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 without changes for fat composition. 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. 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). Moreover, distribution of the fat was modified during the follow-up. A decrease in trunk/peripheral fat ratio (0.77±0.2 vs 0.7±0.17 p<0.001) and an increase in subcutaneous adipose tissue (SAT) (241.3±173.3 vs 264±154.3 p=0.009) were observed at 1 year whereas visceral adipose tissue (VAT) and VAT/SAT ratio did not change.

Conclusion:

Despite weight gain during treatment with IL6 inhibitor, no increase in fat but a modification in fat distribution has been observed. In contrast, muscle gain with increase in lean mass at 1 year suggested that blocking IL6 might be efficient in rheumatoid cachexia and sarcopenia.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/changes-in-body-composition-and-metabolic-profile-during-treatment-with-tocilizumab-in-patients-with-rheumatoid-arthritis/