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Biologics Delay Progression of Crohn's Disease, but Not Early Surgery, in Children
Basavaraj Kerur1, Jason T Machan2, Jason M Shapiro1
1Pediatric Gastroenterology and Nutrition, Hasbro Children Hospital, Providence, Rhode Island; The Warren Alpert Medical School, Brown University, Providence, Rhode Island.
Insights
Pediatric Crohn's disease (CD) patients often need surgery early. Early biologics may slow disease progression to stricturing or penetrating disease, but surgery risk remains high in the first 5 years.
Area of Science:
- Pediatric Gastroenterology
- Inflammatory Bowel Disease Research
- Clinical Epidemiology
Background:
- Crohn's disease (CD) frequently necessitates surgery in pediatric patients within five years of diagnosis.
- Investigating surgical risk and the impact of early biologic therapy in pediatric CD is crucial for optimizing treatment strategies.
Purpose of the Study:
- To determine the 10-year risk of bowel surgery in children diagnosed with Crohn's disease.
- To assess whether early biologic (tumor necrosis factor antagonist) use influences the long-term disease course and progression.
Main Methods:
- Analysis of a registry of 1442 pediatric CD patients diagnosed between 2002 and 2014.
- Data collection included diagnosis, follow-up visits, and hospitalizations for up to 12 years.
- Primary endpoint was the 10-year risk of first bowel surgery; secondary endpoint was the effect of early biologics on disease progression.
Main Results:
- The 10-year risk of first bowel surgery was 26%; the 5-year risk remained stable at 13-14% from 2002-2014.
- Disease behavior at diagnosis was the sole predictor of surgery; inflammatory behavior had the lowest risk.
- Early biologic use (<3 months) was associated with delayed progression to stricturing/penetrating disease, evident after five years, but did not significantly reduce immediate surgery risk.
Conclusions:
- Early surgery is difficult to prevent in pediatric Crohn's disease patients with significant, progressing disease, even with early biologic intervention.
- While early biologics can slow disease progression to more severe forms over time, their impact on preventing surgery in the initial years is limited.
- Treatment decisions regarding early biologics should consider their long-term benefits in disease modification rather than immediate surgical risk reduction.
Background & Aims:
Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course.
Methods:
We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (<3 mo of diagnosis) affected risk of disease progression.
Results:
The 10-year risk of first bowel surgery was 26%. The 5-year risk of bowel surgery did not change from 2002 through 2014, and remained between 13% and 14%. Most surgeries occurred within 3 years from diagnosis. The only predictor of surgery was disease behavior at diagnosis. CD with inflammatory behavior had the lowest risk of surgery compared to stricturing disease, penetrating disease, or both. We associated slowing of disease progression to stricturing or penetrating disease (but not surgery) with early use of biologics, but this effect only became evident after 5 years of disease. Our results indicate that biologics slow disease progression over time (hazard ratio, 0.85; 95% CI, 0.76-0.95).
Conclusions:
In an analysis of data from a registry of pediatric patients with CD, we found that among those with significant and progressing disease at or shortly after presentation, early surgery is difficult to prevent, even with early use of biologics. Early use of biologics (<3 mo of diagnosis) can delay later disease progression to stricturing and/or penetrating disease, but this affect could become evident only years after initial management decisions are made.