High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn’s Disease

Abstract

Background: Obesity is common among patients with pediatric Crohn’s disease (PCD). Some adult studies suggest obese patients respond less well to anti-TNF treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). Methods: The COMBINE trial compared anti-TNF monotherapy to combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI versus BMI Z score > 1, adjusting for prescribed anti-TNF (infliximab or adalimumab), trial treatment assignment (combination versus monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. Results: Of 224 participants (162 infliximab initiators and 62 adalimumab initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among adalimumab initiators [7/10 (70%) vs 12/52 (23%), HR 0.29, p=.007] but not infliximab initiators. Additionally, adalimumab-treated patients with a high BMI had lower adalimumab levels compared to those with normal BMI (median 5.8 ug/mL vs 12.8 ug/mL, p=0.02). Infliximab trough levels did not differ between BMI groups. Conclusions: Overweight and obese patients with PCD are more likely to experience adalimumab treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard adalimumab dosing may be insufficient for overweight children with PCD. Among infliximab initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.