Cost-effectiveness of TPMT Pharmacogenetics (TOPIC)
|ClinicalTrials.gov Identifier: NCT00521950|
Recruitment Status : Completed
First Posted : August 28, 2007
Last Update Posted : March 28, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Inflammatory Bowel Diseases Crohn Disease Ulcerative Colitis||Genetic: TPMT genotyping; Drug: azathioprine or 6-mercaptopurine Drug: azathioprine (AZA) or 6-mercaptopurine (6-MP)||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||853 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Supportive Care|
|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 Start Date :||September 2007|
|Actual Primary Completion Date :||December 2011|
|Actual Study Completion Date :||December 2011|
Experimental: Intervention, TPMT genotyping
Pre-treatment TPMT genotyping to optimize initial thiopurine treatment dose. Intervention is based on the genotype.
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:
Active Comparator: control
Standard thiopurine treatment
Drug: azathioprine (AZA) or 6-mercaptopurine (6-MP)
Patients will be advised a standard initial treatment dose:
- Haematological adverse drug reactions [ Time Frame: 0-5 months ]
- Non-haematological Adverse Drug Reactions [ Time Frame: 0- 5 months ]
- Clinical outcome (disease activity) [ Time Frame: 5 months ]
- Treatment compliance [ Time Frame: 0 to 5 months ]
- TPMT enzym activity [ Time Frame: at baseline ]
- Therapeutic Drug Monitoring of TPMT Metabolites [ Time Frame: week 1 and 8 ]
- Health related quality of life [ Time Frame: 5 months ]
- Cost-efficacy [ Time Frame: 5 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00521950
|Radboud University Medical Center|
|Nijmegen, Gelderland, Netherlands, 6500 HB|
|Oss, Netherlands, 5342 BT|
|Veghel, Netherlands, 5461 AA|
|Study Director:||Barbara Franke, PhD||Radboud University|
|Study Chair:||Hans Scheffer, PhD||Radboud University|
|Principal Investigator:||Corine J van Marrewijk, MSc||Radboud University|
|Principal Investigator:||Dirk J de Jong, MD PhD||Radboud University|
|Study Chair:||Marieke JH Coenen, PhD||Radboud University|
|Study Chair:||Henk-Jan Guchelaar, PhD||Leiden UMC|
|Study Chair:||Luc Derijks, PhD||Maxima MC Veldhoven|
|Study Chair:||Olaf Klungel, PhD||UMC Utrecht|
|Study Chair:||André Verbeek, PhD||Radboud University|
|Study Chair:||Sita Vermeulen, MSc||Radboud University|