Cost-effectiveness of TPMT Pharmacogenetics

Not Applicable

Completed

• Conditions: Crohn Disease; Ulcerative Colitis; Inflammatory Bowel Diseases
• Interventions: Drug: azathioprine (AZA) or 6-mercaptopurine (6-MP)

• Registration Number: NCT00521950
• Lead Sponsor: ZonMw: The Netherlands Organisation for Health Research and Development

Brief 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.

Study Timeline

• Study First Submitted: 2007-08-27
• Study First Submitted QC: 2007-08-27
• Study First Posted: 2007-08-28
• Study Start: 2007-09
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-27
• Last Update Posted: 2014-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 853

Inclusion Criteria

• Age 18 or older
• Diagnosis of a form of IBD
• Indication for azathioprine/6-MP treatment
• Patient giving (written) informed consent

Exclusion Criteria

• Previous treatment with azathioprine/6-MP
• Co-prescription of allopurinol (this treatment blocks xanthine oxidase, an enzyme important for thiopurine metabolism)
• Baseline leukocyte count less then 3x10^9 per litre
• Reduced liver function at baseline
• Reduced renal function at baseline
• Known TPMT phenotype (enzyme activity / Therapeutic Drug Monitoring) or genotype
• Pregnancy or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
control	azathioprine (AZA) or 6-mercaptopurine (6-MP)	Standard thiopurine treatment

Primary Outcome Measures

Name	Time	Method
Haematological adverse drug reactions	0-5 months

Secondary Outcome Measures

Name	Time	Method
Non-haematological Adverse Drug Reactions	0- 5 months
Clinical outcome (disease activity)	5 months
Treatment compliance	0 to 5 months
Therapeutic Drug Monitoring of TPMT Metabolites	week 1 and 8
Health related quality of life	5 months
Cost-efficacy	5 months
TPMT enzym activity	at baseline

Trial Locations

Locations (2)

Bernhoven Hospital; 🇳🇱 Veghel, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Gelderland, Netherlands