Impact of visceral adipose tissue and skeletal muscle on early and long-term biologic treatment failure in Crohn’s disease: A multicenter retrospective cohort study

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BACKGROUND: Crohn's disease (CD) patients exhibit changed body composition, with elevated visceral adipose tissue (VAT) and reduced skeletal muscle (SM). This study aimed to investigate the impact of VAT and SM on the efficacy of CD biologics and develop a predictive model for loss of response. METHODS: This was a multicenter retrospective cohort study. CD patients initially treated with infliximab and ustekinumab were enrolled between January 2018 and December 2023. The visceral fat index (VFI) and skeletal muscle index (SMI) were measured using computed tomography. Patients were divided into 3 groups based on tertiles of VFI (quartile 1 [Q1]: <0.575; Q2: 0.575-0.885; Q3: ≥0.885) and SMI (Q1: <36.4; Q2: 36.4-44.4; Q3: ≥44.4). The primary outcome was loss of response at 52 weeks and the secondary outcome was primary nonresponse after induction. RESULTS: A total of 248 patients were included. The lowest SMI group had higher rates of primary nonresponse (Q1 vs Q2 vs Q3: 15.7% vs 7.2% vs 3.7%; P = .021) and loss of response (Q1 vs Q2 vs Q3: 38.0% vs 17.1% vs 16.5%; P < .001). Higher VFI was linked with increased loss of response (Q1 vs Q2 vs Q3: 12.8% vs 17.1% vs 41.7%; P < .001) and lower mucosal healing rates (Q1 vs Q2 vs Q3: 63.9% vs 40.0% vs 26.9%; P < .001). Elevated VFI (male >0.887, female >0.679) and reduced SMI (male <40.2, female <31.0) were independent risk factors for 52-week loss of response. A predictive model combining body composition parameters and clinical data showed strong performance, with an externally validated area under the curve of area under the curve of 0.902 (95% confidence interval, 0.828-0.975). CONCLUSIONS: Elevated VAT and reduced SM were associated with loss of response in CD biologics. The predictive model integrating body composition parameters demonstrated good performance.

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