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 ReactionsClinical 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
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