Role of Thiopurines in Pediatric Inflammatory Bowel Diseases: A Real-Life Prospective Cohort Study
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Ohad Atia1, Oren Ledder1, Tehila Ben-Moshe1
1Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition.
Insights
Thiopurines demonstrate safety and effectiveness in pediatric inflammatory bowel diseases (IBD) when dose-optimized. This study highlights their viability in treatment plans, particularly for girls with mild-to-moderate IBD.
Area of Science:
- Pediatric Gastroenterology
- Immunopharmacology
- Inflammatory Bowel Disease Research
Background:
- The use of thiopurines for pediatric inflammatory bowel diseases (IBD) is decreasing globally.
- There is a need to understand the real-world outcomes and predictors of response for thiopurine therapy in children.
- Dose optimization strategies are being explored to improve thiopurine efficacy and safety.
Purpose of the Study:
- To evaluate the outcomes of thiopurine therapy in a prospective, real-world cohort of children with IBD.
- To identify predictors of treatment response and remission in pediatric IBD patients receiving thiopurines.
- To assess the safety and effectiveness of dose-optimized thiopurine treatment.
Main Methods:
- A prospective cohort study enrolled children with IBD treated with thiopurines (without biologics).
- Dosing was guided by thiopurine S-methyltransferase activity, clinical response, toxicity, and therapeutic drug monitoring.
- The primary outcome was steroid-free remission (SFR) without treatment escalation at 12 months, analyzed using an intention-to-treat approach.
Main Results:
- 129 children (74% Crohn disease, 26% ulcerative colitis) were included. SFR was achieved in 39% of CD and 39% of UC patients.
- SFR with normalized inflammatory markers (ESR/CRP) was observed in 21% of CD and 27% of UC patients.
- Predictors like mean corpuscular volume/white blood cell ratio and absolute neutrophil count changes correlated with 6-thioguanine levels. In CD, SFR was associated with lower disease activity scores and higher neutrophil count changes at 4 months.
Conclusions:
- Dose-optimized thiopurines are safe and effective in a subset of pediatric IBD patients (21% CD, 27% UC), achieving remission with normalized inflammatory markers.
- Thiopurines remain a valuable therapeutic option for mild-to-moderate pediatric IBD, particularly in girls due to lower lymphoma risk.
- The study provides real-world evidence supporting the continued use of thiopurines within a comprehensive IBD treatment strategy.
Objectives:
Use of thiopurines for inflammatory bowel diseases (IBDs) is declining in some parts of the world. We aimed to explore outcomes of thiopurines and predictors of response in a real-world prospective cohort of children with dose optimization.
Methods:
Children with IBD treated with thiopurines without biologics were enrolled. Dosing was guided by thiopurine S-methyltransferase-activity at baseline and by clinical response and toxicity at 4 months; 1 year into the study, therapeutic drug monitoring at 4 months was also considered in the decision making. The primary outcome was steroid-free remission without treatment escalation by 12 months (SFR), using the intention-to-treat approach.
Results:
A total of 129 children were included (74% Crohn disease [CD] and 26% ulcerative colitis [UC]). SFR was achieved in 37 (39%) CD and 13 (39%) UC patients, and SFR with normal erythrocyte sedimentation rate/C-reactive protein in 20 (21%) and 9 (27%), respectively. At 4 months, mean corpuscular volume/white blood cell ratio and Δ absolute neutrophil count weakly correlated with 6-thioguanine (r = 0.33, P = 0.02 and r = 0.32, P = 0.02, respectively). In CD, SFR was associated with 4-month median weighted Pediatric Crohn Disease Activity Index (2.5 [IQR 0-7.5] in responders vs 5 in nonresponders [0-12.5], P = 0.048) and Δabsolute neutrophil count (1.7 [IQR 0.7-4.1] vs 0.05 [-2.3-0.9]; P = 0.03). Mild drug-related adverse events were recorded in 30 children (22%), 3 required stopping the drug.
Conclusions:
In this real-life prospective cohort using dose optimization, thiopurines were safe and effective in 21% of CD and 27% of UC patients, including normalization of C-reactive protein and erythrocyte sedimentation rate. Thiopurines remain a viable option in the treatment algorithm of mild-moderate pediatric IBD, especially in girls whose risk for lymphoma is lower.
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