NCT00521950

Cost-effectiveness of TPMT Pharmacogenetics

Pharmacogenetic Testing in the Clinical Setting: is Screening for TPMT Genotype a Cost-effective Treatment Strategy? - The First Prospective Randomized Controlled Trial Within the Dutch Health Care System.

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 853 (actual)
• Sponsor: ZonMw: The Netherlands Organisation for Health Research and Development · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Immunosuppressives, e.g. azathioprine (AZA) and 6-mercaptopurine (6-MP), are important in induction of remission and long term treatment of (ulcerative) colitis and Crohn's disease when treatment with 5-aminosalicylates and corticosteroids fails. ADRs to immunosuppressive treatment, including myelosuppression and hepatotoxicity, are frequently (15-30%) observed. Genetic variation in the TPMT gene results in 10-11% of the general population in reduced and in 0.3-0.6% to negligible TPMT enzyme activity. In IBD patients, this genetic variation predicts 25-40% of the haematological ADRs necessitating tempering of thiopurine dose or discontinuation of treatment. Pharmacogenetics aims at providing optimized drug treatment to patients by maximizing efficacy and minimizing adverse drug reactions (ADRs) based on genetic testing. Despite the proven value of pharmacogenetics in clinical practice, its use in medical care is still limited. The best-established example of a pharmacogenetic test is genotyping of thiopurine S-methyltransferase (TPMT) in the treatment of patients with immunosuppressive thiopurines. Nonetheless, it is not used on a large scale in clinical practice so far, which might be due to: insufficient information transfer from research to clinic; lack of cost-effectiveness analyses (CEAs); lack of availability of (or access to) fast and/or cheap genotyping; or lack of test reimbursement by health insurance.

Conditions

• Inflammatory Bowel Diseases
• Crohn Disease
• Ulcerative Colitis

Interventions

Type	Name	Description
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);

Timeline

• Start date: 2007-09-01
• Primary completion: 2011-12-01
• Completion: 2011-12-01
• First posted: 2007-08-28
• Last updated: 2014-03-28

Locations

3 sites across 1 country: Netherlands