Ebach Dawn R, Jester Traci W, Galanko Joseph A, Firestine Ann M, Ammoury Rana, Cabrera Jose, Bass Julie, Minar Phillip, Olano Kelly, Margolis Peter, Sandberg Kelly, Linnville Tiffany M, Kaplan Jess, Pitch Lisa, Steiner Steven J, Bass Dorsey, Moses Jonathan, Adler Jeremy, Gulati Ajay S, Wali Prateek, Pashankar Dinesh, Ivanova Anastasia, Herfarth Hans, Wohl David A, Benkov Keith J, Strople Jennifer, Sullivan Jillian, Tung Jeanne, Molle-Rios Zorela, Saeed Shehzad A, Bousvaros Athos, Kappelman Michael D
Division of Gastroenterology, Hepatology, Pancreatology, and Nutrition, University of Iowa, Iowa City, Iowa, USA.
Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Am J Gastroenterol. 2024 Jun 1;119(6):1110-1116. doi: 10.14309/ajg.0000000000002741. Epub 2024 Mar 6.
Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI).
The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined.
Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 μg/mL, P = 0.02). IFX trough levels did not differ between BMI groups.
Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX 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.
肥胖在小儿克罗恩病（PCD）患者中很常见。一些成人研究表明，肥胖患者对抗肿瘤坏死因子（TNF）治疗的反应较差。本研究旨在比较体重指数（BMI）正常和高的小儿患者的抗TNF反应及抗TNF水平。
COMBINE试验比较了PCD患者中抗TNF单药治疗与甲氨蝶呤联合治疗的效果。在这项二次分析中，比较了BMI正常与BMI Z评分>1的患者的治疗失败时间，并对规定的抗TNF药物（英夫利昔单抗[IFX]或阿达木单抗[ADA]）、试验治疗分配（联合治疗与单药治疗）及相关协变量进行了调整。还检查了不同BMI类别患者的抗TNF水平中位数。
在224名参与者（162名IFX起始治疗者和62名ADA起始治疗者）中，111名（81%）BMI正常，43名（19%）BMI高。高BMI与ADA起始治疗者的治疗失败相关（7/10[70%]对12/52[23%]，风险比0.29，P = 0.007），但与IFX起始治疗者无关。此外，高BMI的ADA治疗患者与BMI正常的患者相比，ADA水平较低（中位数5.8对12.8μg/mL，P = 0.02）。BMI组间IFX谷浓度无差异。
超重和肥胖的PCD患者比BMI正常的患者更易出现ADA治疗失败。较高的BMI与较低的药物谷浓度相关。标准的ADA剂量可能不足以治疗超重的PCD儿童。在IFX起始治疗者中，未观察到临床结局或药物水平的差异，这可能是由于基于体重的给药和/或更多地使用了主动药物监测。
