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6-Thioguanine levels in pediatric IBD patients: adherence is more important than dose

Neal S LeLeiko1, Debra Lobato, Sarah Hagin

  • 1*Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Department of Pediatrics, Hasbro Children's Hospital/The Rhode Island Hospital, Providence, Rhode Island; †Warren Alpert Medical School of Brown University, Providence, Rhode Island; ‡Division of Child and Adolescent Psychiatry, Department of Psychiatry, Hasbro Children's Hospital/The Rhode Island Hospital, Providence, Rhode Island; §Bradley Hasbro Children's Research Center, Providence, Rhode Island; and ‖E. P. Bradley Hospital, East Providence, Rhode Island.

Inflammatory Bowel Diseases
|October 10, 2013
PubMed

Insights

Patient adherence to 6-mercaptopurine (6-MP) significantly impacts thiopurine metabolite levels (6-TGN). Poor adherence, not dose, often explains treatment failure in pediatric inflammatory bowel disease.

Area of Science:

  • Pediatric Gastroenterology
  • Pharmacogenomics
  • Inflammatory Bowel Disease (IBD) Management

Background:

  • Thiopurine immunosuppressants like 6-mercaptopurine (6-MP) are crucial for maintaining remission in pediatric Crohn's disease and ulcerative colitis.
  • Therapeutic success is linked to red blood cell levels of 6-thioguanine (6-TGN), but dose-level correlations remain unclear.

Purpose of the Study:

  • To investigate the relationship between 6-thioguanine (6-TGN) metabolite levels and patient adherence to 6-mercaptopurine (6-MP) in children with IBD.
  • To determine if adherence, rather than prescribed dose, influences therapeutic efficacy.

Main Methods:

  • Utilized electronic monitoring devices to objectively assess adherence to 6-MP in pediatric and adolescent IBD patients.
  • Quantified red blood cell 6-TGN levels and correlated them with adherence data and prescribed doses.

Main Results:

  • Overall adherence to 6-MP was 74.2%, leading to a lack of correlation between prescribed dose and 6-TGN levels.
  • 6-TGN levels significantly correlated with adherence-adjusted 6-MP dose (R²=0.395) and adherence alone (R²=0.478).
  • Concomitant adherence to 5-aminosalicylic acid positively influenced 6-TGN levels, independent of 6-MP adherence, and low 6-MP adherence predicted therapy escalation.

Conclusions:

  • Red blood cell 6-TGN levels directly reflect the actual dose of thiopurine taken, not the prescribed dose.
  • Poor patient adherence is a primary driver of treatment failure with thiopurines in pediatric IBD.
  • Novel strategies for monitoring and improving adherence are essential, and future trials must incorporate adherence assessments.
Abstract

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