A High Visceral-to-Skeletal Muscle Area Ratio on Cross-Sectional Imaging Is Associated With Failure of Standard Ustekinumab Doses: A Multicenter Study

Abstract

INTRODUCTION: Anti-interleukin 12/23 agents have shown greater durability in response compared with anti-tumor necrosis factor α agents. Data on the association between body composition (BC) or body mass index (BMI) and ustekinumab's therapeutic response is limited. We aimed to evaluate the impact of BC on time to failing standard doses of ustekinumab in patients with Crohn's disease (CD). METHOD: Patients with CD aged 16 years and older from 2 tertiary centers were studied retrospectively. Included patients had abdominal imaging within 6 months of ustekinumab induction and were followed until April 30, 2022. An experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat area and skeletal muscle area at the mid L3 vertebral level, with values corrected for height2 to derive respective indices (visceral fat index [VFI], skeletal muscle index [SMI]) and the VFI:SMI ratio. RESULTS: Ninety-nine patients met inclusion criteria. The mean age at ustekinumab induction was 46.6 (±1.6) years. The median BMI (interquartile range) was 26.5 (22.6–30.8). Twenty-four patients (24.2%) did not respond or lost response to standard doses of ustekinumab over the follow-up duration. A younger age (hazard ratio 0.96, 95% confidence interval 0.94–0.99, P = 0.01) and a VFI:SMI ratio >1.6 (hazard ratio 4.65, 95% confidence interval 1.73–12.45, P = 0.002) were both associated with a shorter time to failing ustekinumab at standard doses on multivariate analysis. BMI, notably, had no association with the primary outcome. DISCUSSION: A high VFI:SMI ratio is associated with an increased risk of failing standard doses of ustekinumab. BC measurements derived from cross-sectional imaging at the start of ustekinumab therapy is a useful indicator for therapeutic durability.