PReS-FINAL-2188: Insulin sensitivity is improved in sjia children with insulin resistance after tocilizumab treatment: results from the tender study

Abstract

Introduction: In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin-6 (IL-6) is postulated to play a mechanistic role in IR. Objectives: To evaluate the degree of IR among children with systemic juvenile idiopathic arthritis (sJIA) and whether treatment with tocilizumab (TCZ) results in attenuation of IR in sJIA. Methods: Patients (pts) from TENDER1 were included if baseline and wk 6 fasting insulin were measured. Glucocorticoid tapering was not permitted until wk 6. Insulin sensitivity was quantified using the homeostatic model of insulin resistance (HOMA-IR). Pts were classified as having IR if their HOMA-IR was >2.2 U. Change in HOMA-IR after 6 wks was assessed using paired t-test. Baseline associations with HOMA-IR and factors predicting change of HOMA-IR from baseline were assessed using regression analyses. Factors changing in association with HOMA-IR change were assessed. Results: 92 pts with sJIA were analysed. 62 were randomised to TCZ and 30 to placebo, 12 of whom required escape therapy with TCZ by wk 6. At baseline, 40 pts (43%) had IR. Baseline HOMA-IR was associated with higher standardised body mass index and higher IL-6 levels (b-coefficient [95% CI]: 0.20 [0.05, 0.35] and 0.019 [0.001, 0.038], respectively) but not with JADAS, CRP, active joint count or presence of fever. Of the 74 pts who received TCZ, 34 (46%) had IR at baseline, including 4 pts who escaped from the placebo arm, compared with 6/18 (33%) who received only placebo. IR pts treated with TCZ but not placebo had significant reductions in HOMA-IR at wk 6 (Table). Across all IR pts, improvement in JADAS and active joint count was not associated with improvement in HOMA-IR (b-coefficient [95% CI]: 0.04 [-0.07, 0.14] and 0.08 [-0.06, 0.22], respectively). Conclusion: After only 6 wks of TCZ treatment, HOMA-IR was improved in IR pts with sJIA in the presence of unchanged glucocorticoid dose. These data support a mechanistic contribution of IL-6 to IR in vivo in humans. (Table Presented).