Effect of tumour necrosis factor inhibitor or interleukin-6 inhibitor treatment on exercise-induced reductions in visceral adipose tissue mass in patients at high risk of cardiovascular disease

Abstract Objectives Excess visceral adipose tissue (VAT) mass increases cardiovascular disease (CVD) risk. Exercise supports overall health and VAT mass reduction in rheumatoid arthritis (RA) – which is a high-risk population for CVD. Unlike tumour necrosis factor (TNF), interleukin-6 (IL-6) is upregulated following exercise and may mediate the reduction in VAT mass. Since treatment strategies for patients with RA include the inhibition of IL-6 (IL-6i) or TNF (TNFi), the hypothesis of this study was that in patients with RA treatment with IL-6i abolishes the cardioprotective effects of exercise on VAT reduction compared to patients with TNFi treatment. Methods In this secondary analysis of a randomized controlled trial, 69 patients with RA in stable TNFi (n=40) or IL-6i (n=29) therapy were stratified for treatment and assigned to a 12-week supervised high intensity interval training (HIIT) intervention or no exercise (control). The primary objective was to investigate the effects of TNFi or IL-6i therapy on exercise-induced changes in VAT mass (g) from baseline to 12-week follow-up, assessed by abdominal magnetic resonance imaging. Results Compared to control, HIIT did not change VAT mass in either TNFi (-34 g 95% CI, -208 to 140 g; p=0.69) or IL-6i (-9 g 95% CI, -228 to 211 g; p=0.93) treatment groups. There was no interaction between IL-6i and exercise on changes in VAT mass (25 g 95% CI, -255 to 306 Pinteraction= 0.85). Exercise-induced changes to the subcutaneous adipose tissue and insulin sensitivity were negligible and not significantly different between treatment modalities. Conclusions A 12-week HIIT intervention did not reduce VAT mass in patients with RA at high risk of CVD in treatment with either TNFi or IL-6i.Change in VAT mass (g)