Cost-effectiveness of TPMT Pharmacogenetics

Summary

The purpose of this study is to determine whether thiopurine S-methyltransferase (TPMT) genotyping prior to thiopurine use is cost-effective in patients with inflammatory bowel disease (IBD) in need of immune suppression.

The study is designed to test the hypothesis that optimization of initial thiopurine dose based on pre-treatment TPMT genotyping will maximize treatment efficacy and minimize adverse drug reactions (ADRs) resulting in reduced costs.

Conditions

• Inflammatory Bowel Diseases
• Crohn Disease
• Ulcerative Colitis

Interventions

GENETIC

TPMT genotyping; Drug: azathioprine or 6-mercaptopurine

Assessment of the polymorphisms G238C, G460A, and A719G in a venous blood sample to identify functional genetic variants (TPMT\*2, \*3A, \*3C) of the TPMT gene (chromosome 6) associated with reduced or negligible TPMT enzyme activity. Patients are advised an initial treatment dose based on the enzyme activity: * Normal: AZA 2-2.5 mg/kg/day or 6-MP 1-1.5 mg/kg/day (standard care); * Reduced: AZA 1-1.25 mg/kg/day or 6-MP 0.5-0.75 mg/kg/day; * Negligible: AZA 0-0.2 mg/kg/day or 6-MP 0-0.1 mg/kg/day;

DRUG

azathioprine (AZA) or 6-mercaptopurine (6-MP)

Patients will be advised a standard initial treatment dose: * AZA 2-2.5 mg/kg/day or 6-MP 1-1.5 mg/kg/day (standard care);

Sponsors & Collaborators

• Radboud University Medical Center

  collaborator OTHER

• ZonMw: The Netherlands Organisation for Health Research and Development

  lead OTHER

Principal Investigators

• Barbara Franke, PhD · Radboud University Medical Center

• Hans Scheffer, PhD · Radboud University Medical Center

• Corine J van Marrewijk, MSc · Radboud University Medical Center

• Dirk J de Jong, MD PhD · Radboud University Medical Center

• Marieke JH Coenen, PhD · Radboud University Medical Center

• Henk-Jan Guchelaar, PhD · Leiden UMC

• Luc Derijks, PhD · Maxima MC Veldhoven

• Olaf Klungel, PhD · UMC Utrecht

• André Verbeek, PhD · Radboud University Medical Center

• Sita Vermeulen, MSc · Radboud University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-09-30

Primary Completion

2011-12-31

Completion

2011-12-31

Countries

• Netherlands

Study Locations