Related Experiment Video
Updated: Feb 12, 2026
DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat
Published on: February 27, 2014
Thiopurine Optimization Through Combination With Allopurinol in Children With Inflammatory Bowel Diseases
Mark R Serpico1,2, Ross Maltz1,3, Wallace Crandall1,3
1Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus.
Insights
Reduced-dose thiopurines combined with allopurinol effectively managed inflammatory bowel diseases (IBDs) in children by improving liver function and increasing therapeutic drug levels. This approach also reduced corticosteroid use and enhanced remission rates in pediatric IBD patients.
Area of Science:
- Pediatric Gastroenterology
- Pharmacogenomics
- Inflammatory Bowel Disease Treatment
Background:
- Thiopurines are standard for maintaining remission in pediatric inflammatory bowel diseases (IBDs).
- Drug metabolism variations can lead to hepatotoxicity or altered therapeutic effects.
- Optimizing thiopurine therapy is crucial for improving outcomes in children with IBD.
Purpose of the Study:
- To evaluate the efficacy of reduced thiopurine dosing combined with allopurinol in children with IBD.
- To assess the impact of this combination therapy on hepatotoxicity, drug metabolite levels, and clinical outcomes.
- To describe the center's experience with thiopurine optimization in pediatric IBD patients.
Main Methods:
- Retrospective review of pediatric patients (2-21 years) with IBD treated with thiopurines/allopurinol (2008-2015).
- Exclusion of patients previously treated with anti-tumor necrosis factor therapy.
- Collection of demographic data, liver transaminase levels, 6-thioguanine (6-TG) and 6-methylmercaptopurine metabolite levels, physician global assessment, and corticosteroid use at baseline, 6, and 12 months.
Main Results:
- 62% of patients (32/52) remained on the combination therapy for 12 months.
- Patients on combination therapy showed reduced liver enzymes (AST, ALT) and increased 6-TG levels at 6 and 12 months (P<0.001).
- Corticosteroid use decreased (P<0.001), and remission rates improved (P=0.013 at 6 months, P=0.003 at 12 months) in patients remaining on therapy.
Conclusions:
- Reduced-dose thiopurines with allopurinol improved hepatotoxicity and 6-TG levels in pediatric IBD patients.
- This combination therapy led to decreased corticosteroid use and improved remission rates for children remaining on treatment for a year.
- Approximately 40% of patients required a change in therapy within 12 months, indicating a need for individualized treatment adjustments.
Objectives:
Thiopurines are commonly used in the maintenance of remission for children with inflammatory bowel diseases (IBDs). Variation in drug metabolism may affect hepatotoxicity or therapeutic effect. We aimed to describe our center's experience with thiopurine optimization through the use of reduced thiopurine dosing in combination with allopurinol upon hepatotoxicity, drug metabolite levels, and clinical outcomes in children with IBD.
Methods:
Patients aged 2 to 21 years with IBD treated with the combination of thiopurines/allopurinol between 2008 and 2015 were retrospectively reviewed. Patients previously treated with antitumor necrosis factor therapy were excluded. Demographic data, transaminase levels (aspartate transaminase, alanine transaminase), drug metabolites levels (6-thioguanine [6-TG], 6-methylmercaptopurine), physician global assessment, and corticosteroid use were recorded at baseline, 6, and 12 months.
Results:
Fifty-two patients (29 girls, 56%) met inclusion criteria. Thirty-two of 52 (62%) remained on the combination for 12 months. In those remaining on the thiopurine/allopurinol combination, median alanine transaminase and aspartate transaminase levels were reduced (P < 0.001) and median 6-TG levels were increased (P < 0.001) at both 6 and 12 months. Corticosteroid use was decreased at both 6 (P < 0.001) and 12 months (P < 0.001) compared to use at baseline. Remission rates also improved at both 6 (P = 0.013) and 12 months (P = 0.003). Twenty of the 52 patients (38%) had discontinued the thiopurine/allopurinol combination within 12 months of initiation with 17 of 52 (33%) initiating antitumor necrosis factor therapy.
Conclusions:
Low-dose thiopurines in combination with allopurinol improved hepatotoxicity and increased 6-TG levels in children with IBD. Corticosteroid use was reduced and remission rates improved in those patients remaining on this combination for 1 year. However, approximately 40% of patients required a change in therapy within 12 months.
More Related Videos
Related Concept Videos
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:21Inflammatory Bowel Disease V: Surgical Management
Here are some common surgical interventions for IBD:
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...