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Cost-effectiveness of TPMT Pharmacogenetics

Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis

Intervention: TPMT genotyping; Drug: azathioprine or 6-mercaptopurine (Genetic); azathioprine (AZA) or 6-mercaptopurine (6-MP) (Drug)

Phase: N/A

Status: Completed

Sponsored by: ZonMw: The Netherlands Organisation for Health Research and Development

Official(s) and/or principal investigator(s):
Barbara Franke, PhD, Study Director, Affiliation: Radboud University
Hans Scheffer, PhD, Study Chair, Affiliation: Radboud University
Corine J van Marrewijk, MSc, Principal Investigator, Affiliation: Radboud University
Dirk J de Jong, MD PhD, Principal Investigator, Affiliation: Radboud University
Marieke JH Coenen, PhD, Study Chair, Affiliation: Radboud University
Henk-Jan Guchelaar, PhD, Study Chair, Affiliation: Leiden UMC
Luc Derijks, PhD, Study Chair, Affiliation: Maxima MC Veldhoven
Olaf Klungel, PhD, Study Chair, Affiliation: UMC Utrecht
André Verbeek, PhD, Study Chair, Affiliation: Radboud University
Sita Vermeulen, MSc, Study Chair, Affiliation: Radboud University

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.

Clinical Details

Official title: 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.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Primary outcome: Haematological adverse drug reactions

Secondary outcome:

Non-haematological Adverse Drug Reactions

Clinical outcome (disease activity)

Treatment compliance

TPMT enzym activity

Therapeutic Drug Monitoring of TPMT Metabolites

Health related quality of life

Cost-efficacy

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

Bernhoven Hospital, Oss 5342 BT, Netherlands

Bernhoven Hospital, Veghel 5461 AA, Netherlands

Radboud University Medical Center, Nijmegen, Gelderland 6500 HB, Netherlands

Additional Information

Department of Human Genetics Nijmegen

Starting date: September 2007
Last updated: March 27, 2014

Page last updated: August 23, 2015

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