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Progression of Pediatric Crohn's Disease Is Associated With Anti-Tumor Necrosis Factor Timing and Body Mass Index
Duke Geem1, David Hercules2, Ranjit S Pelia2
1Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Healthcare of Atlanta, Atlanta, Georgia.
Insights
Early anti-tumor necrosis factor (aTNF) therapy may reduce Crohn's disease progression in children. Lack of body mass index z-score normalization is linked to higher surgery risk and inflammation.
Area of Science:
- Pediatric Gastroenterology
- Inflammatory Bowel Disease Research
- Biologics Therapy
Background:
- Pediatric Crohn's disease (CD) can progress to complicated stricturing or penetrating behaviors.
- Understanding factors influencing disease progression in the era of anti-tumor necrosis factor (aTNF) therapy is crucial.
Purpose of the Study:
- To investigate the risk of developing complicated disease behaviors or requiring surgery in pediatric CD patients.
- To analyze the impact of aTNF therapy timing and body mass index z-score (BMIz) normalization on disease outcomes.
Main Methods:
- Analysis of 5-year longitudinal data from 1075 newly diagnosed pediatric CD patients.
- Utilized Cox proportional hazard regression and log-rank analyses to assess risks.
- Correlated ileal gene expression with clinical outcomes.
Main Results:
- Stricturing complications increased from 2.98% to 10.60% over 5 years.
- Early aTNF exposure (within 3 months) and baseline non-inflammatory disease (L2) reduced progression to stricturing (B2).
- For patients with low BMIz, normalization within 6 months decreased surgery risk; baseline B2/B3 disease increased surgery risk. Patients lacking BMIz normalization showed enrichment for inflammatory genes.
Conclusions:
- Initiating aTNF therapy within 3 months of diagnosis may mitigate the progression to stricturing disease in pediatric CD.
- Failure to normalize BMIz within 6 months is associated with increased surgical risk and a pro-inflammatory gene expression profile.
Background & Aims:
The evolution of complicated pediatric Crohn's disease (CD) in the era of anti-tumor necrosis factor (aTNF) therapy continues to be described. Because CD progresses from inflammatory to stricturing (B2) and penetrating (B3) disease behaviors in a subset of patients, we aimed to understand the risk of developing complicated disease behavior or undergoing surgery in relation to aTNF timing and body mass index z-score (BMIz) normalization.
Methods:
Multicenter, 5-year longitudinal data from 1075 newly diagnosed CD patients were analyzed. Descriptive statistics, univariate and stepwise multivariate Cox proportional hazard regression (CPHR), and log-rank analyses were performed for risk of surgery and complicated disease behaviors. Differential gene expression from ileal bulk RNA sequencing was correlated with outcomes.
Results:
Stricturing complications had the largest increase: from 2.98% to 10.60% over 5 years. Multivariate CPHR showed aTNF exposure within 3 months from diagnosis (hazard ratio [HR], 0.33; 95% CI, 0.15-0.71) and baseline L2 disease (HR, 0.29; 95% CI, 0.09-0.92) to be associated with reduced B1 to B2 progression. For children with a low BMIz at diagnosis (n = 294), multivariate CPHR showed BMIz normalization within 6 months of diagnosis (HR, 0.47; 95% CI, 0.26-0.85) and 5-aminosalicyclic acid exposure (HR, 0.32; 95% CI, 0.13-0.81) were associated with a decreased risk for surgery while B2 (HR, 4.20; 95% CI, 1.66-10.65) and B2+B3 (HR, 8.24; 95% CI, 1.08-62.83) at diagnosis increased surgery risk. Patients without BMIz normalization were enriched for genes in cytokine production and inflammation.
Conclusions:
aTNF exposure up to 3 months from diagnosis may reduce B2 progression. In addition, lack of BMIz normalization within 6 months of diagnosis is associated with increased surgery risk and a proinflammatory transcriptomic profile.
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