Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-27T17:32:06.915Z Has data issue: false hasContentIssue false
  • English
  • Français

Avoiding adverse drug reactions by pharmacogenetic testing: A systematic review of the economic evidence in the case of TPMT and AZA-induced side effects

Published online by Cambridge University Press:  04 July 2008

Amelia Compagni ,
Simona Bartoli ,
Bernhard Buehrlen ,
Giovanni Fattore ,
Dolores Ibarreta  and
Emma Gutierrez de Mesa
Amelia Compagni
Affiliation:
Università Bocconi
Simona Bartoli
Affiliation:
Università Bocconi
Bernhard Buehrlen
Affiliation:
Fraunhofer Institute for Systems and Innovation Research
Giovanni Fattore
Affiliation:
Università Bocconi
Dolores Ibarreta
Affiliation:
Institute for Prospective Technological Studies
Emma Gutierrez de Mesa
Affiliation:
European Centre for Disease Prevention and Control
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives: The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing.

Methods: A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted.

Results: Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered €2,116 as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (€68) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to €5,300.

Conclusions: Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.

Keywords

Pharmacogenetic testingDrug metabolismAZA-induced adverse drug reactionsTPMT deficiencyNeutropenia
Type
GENERAL ESSAYS
Information
International Journal of Technology Assessment in Health Care , Volume 24 , Issue 3 , July 2008 , pp. 294 - 302
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Colombel, J, Ferrari, N, Debuysere, H, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000;118:1025–1030.CrossRefGoogle ScholarPubMed
2. Connell, WR, Kamm, MA, Ritchie, JK, et al. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut. 1993;34:1081–1085.CrossRefGoogle ScholarPubMed
3. Dubinsky, MC, Reyes, E, Ofman, J, et al. A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol. 2005;100:2239–2247.CrossRefGoogle ScholarPubMed
4. European Commission. Pharmacogenetics and pharmacogenomics: State-of-the-art and potential socio-economic impact in the EU. EUR22214. Brussels: European Commission; 2006.Google Scholar
5. Flowers, CR, Veenstra, D. The role of cost-effectiveness analysis in the era of pharmacogenomics. Pharmacoeconomics. 2004;22:481–493.CrossRefGoogle ScholarPubMed
6. Gearry, RB, Barclay, ML, Burt, MJ, et al. Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease. Pharmacoepidemiol Drug Saf. 2004;13:563–567.CrossRefGoogle Scholar
7. Gisbert, JP, Gonzalez-Lama, Y, Mate, J. Thiopurine-induced liver injury in patients with inflammatory bowel disease: A systematic review. Am J Gastroenterol. 2007;102:1518–1527.CrossRefGoogle ScholarPubMed
8. Haddow, JE, Palomaki, GE. ACCE: A model process for evaluating data on emerging genetic tests. In: Human genome epidemiology: A scientific foundation for using genetic information to improve health and prevent disease. Oxford: Oxford University Press; 2003.Google Scholar
9. Hopkins, MM, Ibarreta, D, Gaisser, S, et al. Putting pharmacogenetics into practice. Nat Biotechnol. 2006;24:403–410.CrossRefGoogle ScholarPubMed
10. Hughes, DA, Pirmohamed, M. Warfarin pharmacogenetics: Economic considerations. Pharmacoeconomics. 2007;25:899–902.CrossRefGoogle ScholarPubMed
11. Lazarou, J, Pomeranz, BH, Corey, PN. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA. 1998;279:1200–1205.CrossRefGoogle ScholarPubMed
12. Marra, CA, Esdaile, JM, Anis, AH. Practical pharmacogenetics: The cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine. J Rheumatol. 2002;29:2507–2512.Google ScholarPubMed
13. Oh, KT, Anis, AH, Bae, SC. Pharmacoeconomic analysis of thiopurine methyltransferase polymorphism screening by polymerase chain reaction for treatment with azathioprine in Korea. Rheumatology (Oxford). 2004;43:156–163.CrossRefGoogle ScholarPubMed
14. Payne, K, Newman, W, Fargher, E, et al. TPMT testing in rheumatology: Any better than routine monitoring? Rheumatology (Oxford). 2007;46:727–729.CrossRefGoogle ScholarPubMed
15. Phillips, KA, Van Bebber, SL. Measuring the value of pharmacogenomics. Nat Rev Drug Discov. 2005;4:500–509.CrossRefGoogle ScholarPubMed
16. Phillips, KA, Veenstra, DL, Oren, E, et al. Potential role of pharmacogenomics in reducing adverse drug reactions: A systematic review. JAMA. 2001;286:2270–2279.CrossRefGoogle ScholarPubMed
17. Prashker, MJ, Meenan, RF. The total costs of drug therapy for rheumatoid arthritis. A model based on costs of drug, monitoring, and toxicity. Arthritis Rheum. 1995;38:318–325.CrossRefGoogle Scholar
18. Priest, VL, Begg, EJ, Gardiner, SJ, et al. Pharmacoeconomic analyses of azathioprine, methotrexate and prospective pharmacogenetic testing for the management of inflammatory bowel disease. Pharmacoeconomics. 2006;24:767–781.CrossRefGoogle ScholarPubMed
19. Robertson, JA, Brody, B, Buchanan, A, et al. Pharmacogenetic challenges for the health care system. Health Aff (Millwood). 2002;21:155–167.CrossRefGoogle ScholarPubMed
20. Sanderson, J, Ansari, A, Marinaki, T, et al. Thiopurine methyltransferase: Should it be measured before commencing thiopurine drug therapy? Ann Clin Biochem. 2004;41:294–302.CrossRefGoogle ScholarPubMed
21. Schutz, E, Gummert, J, Mohr, F, et al. Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet. 1993;341:436.CrossRefGoogle ScholarPubMed
22. Shah, J. Criteria influencing the clinical uptake of pharmacogenomic strategies. BMJ. 2004;328:1482–1486.CrossRefGoogle ScholarPubMed
23. Sies, C, Florkowski, C, George, P, et al. Measurement of thiopurine methyl transferase activity guides dose-initiation and prevents toxicity from azathioprine. N Z Med J. 2005;118:U1324.Google ScholarPubMed
24. Tavadia, SM, Mydlarski, PR, Reis, MD, et al. Screening for azathioprine toxicity: A pharmacoeconomic analysis based on a target case. J Am Acad Dermatol. 2000;42:628–632.CrossRefGoogle ScholarPubMed
25. Teml, A, Schaeffeler, E, Herrlinger, KR, et al. Thiopurine treatment in inflammatory bowel disease: Clinical pharmacology and implication of pharmacogenetically guided dosing. Clin Pharmacokinet. 2007;46:187–208.CrossRefGoogle ScholarPubMed
26. Timmer-Bonte, JN, Adang, EM, Termeer, E, et al. Modeling the cost effectiveness of secondary febrile neutropenia prophylaxis during standard-dose chemotherapy. J Clin Oncol. 2008;26:290–296.CrossRefGoogle ScholarPubMed
27. Van Den Akker-van Marle, ME, Gurwitz, D, Detmar, SB, et al. Cost-effectiveness of pharmacogenomics in clinical practice: A case study of thiopurine methyltransferase genotyping in acute lymphoblastic leukemia in Europe. Pharmacogenomics. 2006;7:783–792.CrossRefGoogle ScholarPubMed
28. Walmsley, TA, Florkowski, CM, George, PM, et al. Thiopurine methyltransferase activity and azathioprine. N Z Med J. 2002;115:302.Google ScholarPubMed
29. WHO, Collaborating Center in International Drug Monitoring. Definitions- as adopted by national centers participating in the WHO international drug monitoring program. BMJ. 1992;304:465.Google Scholar
30. Winter, JW, Gaffney, D, Shapiro, D, et al. Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2007;25:1069–1077.CrossRefGoogle ScholarPubMed
31. Winter, J, Walker, A, Shapiro, D, et al. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease. Aliment Pharmacol Ther. 2004;20:593–599.CrossRefGoogle ScholarPubMed
32. Wolf, CR, Smith, G, Smith, RL. Science, medicine, and the future: Pharmacogenetics. BMJ. 2000;320:987–990.CrossRefGoogle ScholarPubMed