Author information

1 Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus OH.

2 Boonshoft School of Medicine, Wright State University, Dayton OH.

3 The Ohio State University College of Medicine, Columbus OH.

4 The Center for Innovation in Pediatric Practice, The Research Institute, Nationwide Children's Hospital, Columbus OH.

5 Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of UPMC, Pittsburgh PA.

Abstract

OBJECTIVES: Thiopurines are commonly used in the maintenance of remission for children with inflammatory bowel diseases (IBD). Variation in drug metabolism may impact 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 2-21 years with IBD treated with the combination of thiopurines/allopurinol between 2008-2015 were retrospectively reviewed. Patients previously treated with anti-tumor necrosis factor (TNF) therapy were excluded. Demographic data, transaminase levels (AST, ALT), drug metabolites levels (6-TG, 6-MMP), physician global assessment (PGA), and corticosteroid use were recorded at baseline, 6 and 12 months.

RESULTS: Fifty-two patients (29 female, 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 ALT and AST 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 17/52 (33%) initiating anti-TNF 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 one year. However, nearly 40% of patients required a change in therapy within 12 months.