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Published in: PharmacoEconomics 8/2006

01-08-2006 | Original Research Article

Pharmacoeconomic Analyses of Azathioprine, Methotrexate and Prospective Pharmacogenetic Testing for the Management of Inflammatory Bowel Disease

Authors: Virginia L. Priest, Professor Evan J. Begg, Sharon J. Gardiner, Christopher M. A. Frampton, Richard B. Gearry, Murray L. Barclay, David W. J. Clark, Paul Hansen

Published in: PharmacoEconomics | Issue 8/2006

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Abstract

Objectives: To compare the cost effectiveness of azathioprine (AZA), methotrexate (MTX) and no immunosuppression for maintaining remission of moderate to severe inflammatory bowel disease (IBD) in New Zealand Caucasians, and to determine whether prospective testing for poor metabolisers of AZA by genotype or phenotype is cost effective.
Methods: Pharmacoeconomic models were developed to compare treatment costs and effects (QALYs) in theoretical populations of 1000 IBD patients over a 1-year period. Efficacy and tolerability profiles for AZA and MTX were taken from the literature. The costs (year 2004 values) of the drugs and treatment of adverse effects were estimated from New Zealand drug and service costs. Representations of the patients’ health-related quality of life (HR-QOL) were obtained from clinicians via the EQ-5D health state classification system and valued using the New Zealand EQ-5D social tariff. The effects of genotyping or phenotyping a population for thiopurine methyltransferase (TPMT) status were compared using the prevalence of TPMT deficiency in Caucasians, the relative risks of neutropenia and the associated costs.
Results: Net cost savings (vs no immunosuppressant treatment) of approximately $NZ2.5 million and $NZ1 million were realised for AZA and MTX, respectively, for the theoretical 1000 patients, and AZA generated 877 QALYs compared with 633 for MTX. Phenotype and genotype testing generated net cost savings (vs no testing) of $NZ120 000 and $NZ11 000, respectively. Savings related to phenotype tests were greater because of the lower assay costs of phenotype testing and a greater likelihood of pre-empting neutropenia.
Conclusion: Our model suggests that both MTX and AZA may generate significant net cost savings and benefits for patients with IBD in New Zealand, with AZA likely to be more cost effective than MTX. Prospective testing for poor metabolisers of AZA may also be cost effective, with phenotype testing likely to be more cost effective than genotype testing.
Literature
1.
go back to reference Janowitz HD. Inflammatory bowel disease: a clinical approach. New York: Oxford University Press, 1994: 8–158 Janowitz HD. Inflammatory bowel disease: a clinical approach. New York: Oxford University Press, 1994: 8–158
3.
go back to reference Rampton DS, Shanahan F. Inflammatory bowel disease. Oxford: Health Press, 2000 Rampton DS, Shanahan F. Inflammatory bowel disease. Oxford: Health Press, 2000
4.
go back to reference Silverstein MD, Loftus EV, Sandborn WJ, et al. Clinical course and costs of care for Crohn’s Disease: Markov model analysis of a population-based cohort. Gastroenterology 1999; 117: 49–57PubMedCrossRef Silverstein MD, Loftus EV, Sandborn WJ, et al. Clinical course and costs of care for Crohn’s Disease: Markov model analysis of a population-based cohort. Gastroenterology 1999; 117: 49–57PubMedCrossRef
5.
go back to reference Card T, Hubbard R, Logan RFA. Mortality in inflammatory bowel disease: a population based cohort study. Gastroenterology 2003; 125: 1583–90PubMedCrossRef Card T, Hubbard R, Logan RFA. Mortality in inflammatory bowel disease: a population based cohort study. Gastroenterology 2003; 125: 1583–90PubMedCrossRef
6.
go back to reference Arndt C, Balis F, McCully L. Bioavailability of low-dose verses lowdose 6-mercaptopurine. Clin Pharmacol Ther 1988; 45 (5): 588–91CrossRef Arndt C, Balis F, McCully L. Bioavailability of low-dose verses lowdose 6-mercaptopurine. Clin Pharmacol Ther 1988; 45 (5): 588–91CrossRef
7.
go back to reference Van Os E, Zins BJ, Sandborn WJ, et al. Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. Gut 1996; 39 (1): 63–8PubMedCrossRef Van Os E, Zins BJ, Sandborn WJ, et al. Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. Gut 1996; 39 (1): 63–8PubMedCrossRef
8.
go back to reference Feagan BG, Alfadhli A. Methotrexate in inflammatory bowel disease. Gastroenterol Clin North Am 2004; 33: 407–20PubMedCrossRef Feagan BG, Alfadhli A. Methotrexate in inflammatory bowel disease. Gastroenterol Clin North Am 2004; 33: 407–20PubMedCrossRef
9.
go back to reference Pearson DC, May GR, Fick G, et al. Azathioprine for maintenance of remission in Crohn’s disease. Available in The Cochrane Library [database on disk and CD-ROM]. Updated quaterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2004 Pearson DC, May GR, Fick G, et al. Azathioprine for maintenance of remission in Crohn’s disease. Available in The Cochrane Library [database on disk and CD-ROM]. Updated quaterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2004
10.
go back to reference Markowitz JF. Therapeutic efficacy and safety of 6-mercaptopurine and azathioprine in patients with Crohn’s Disease. Rev Gastroenterol Disord 2003; 3 Suppl. 1: S23–9PubMed Markowitz JF. Therapeutic efficacy and safety of 6-mercaptopurine and azathioprine in patients with Crohn’s Disease. Rev Gastroenterol Disord 2003; 3 Suppl. 1: S23–9PubMed
11.
go back to reference Gearry RB, Barclay M, Burt MJ, et al. Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease. Pharmacoepidemiol Drug Saf 2004; 13: 563–7PubMedCrossRef Gearry RB, Barclay M, Burt MJ, et al. Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease. Pharmacoepidemiol Drug Saf 2004; 13: 563–7PubMedCrossRef
12.
go back to reference Fraser AG, Morton D, McGovern D, et al. The efficacy of methotrexate for maintaining remission in inflammatory bowel disease. Aliment Phannacol Ther 2002; 16: 693–7CrossRef Fraser AG, Morton D, McGovern D, et al. The efficacy of methotrexate for maintaining remission in inflammatory bowel disease. Aliment Phannacol Ther 2002; 16: 693–7CrossRef
13.
go back to reference Umann M, Chamoit-Prieur C, Mesnard B. Methotrexate for the treatment of refractory Crohn’s disease. Aliment Pharmacol Ther 1996; 10: 309–14CrossRef Umann M, Chamoit-Prieur C, Mesnard B. Methotrexate for the treatment of refractory Crohn’s disease. Aliment Pharmacol Ther 1996; 10: 309–14CrossRef
14.
go back to reference Lemann M, Zenjari T, Bouhnik Y, et al. Methotrexate in Crohn’s disease: long-term efficacy and toxicity. Am J Gastroenterol 2000; 95 (7): 1730–4PubMed Lemann M, Zenjari T, Bouhnik Y, et al. Methotrexate in Crohn’s disease: long-term efficacy and toxicity. Am J Gastroenterol 2000; 95 (7): 1730–4PubMed
15.
go back to reference Schnabel A, Gross WL. Low dose methotrexate in rheumatic diseases: efficacy, side effects, and risk factors for side effects. Semin Arthritis Rheum 1994; 23: 310–27PubMedCrossRef Schnabel A, Gross WL. Low dose methotrexate in rheumatic diseases: efficacy, side effects, and risk factors for side effects. Semin Arthritis Rheum 1994; 23: 310–27PubMedCrossRef
16.
go back to reference Dubinsky M, Reyeas E, Of man J, et al. A cost-effectiveness analysis of alternative disease management strategies in patients treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol 2005; 100: 2239–47PubMedCrossRef Dubinsky M, Reyeas E, Of man J, et al. A cost-effectiveness analysis of alternative disease management strategies in patients treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol 2005; 100: 2239–47PubMedCrossRef
17.
go back to reference Gardiner SJ, Begg EJ, Barclay ML, et al. Genetic polymorphism and outcomes with azathioprine and 6-mercaptopurine. Adverse Drug React Toxicol Rev 2000; 19 (4): 293–312PubMed Gardiner SJ, Begg EJ, Barclay ML, et al. Genetic polymorphism and outcomes with azathioprine and 6-mercaptopurine. Adverse Drug React Toxicol Rev 2000; 19 (4): 293–312PubMed
18.
go back to reference Schaeffeler E, Fischer C, Brockmeier D, et al. Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a larger population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics 2004; 14 (7): 407–17PubMedCrossRef Schaeffeler E, Fischer C, Brockmeier D, et al. Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a larger population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics 2004; 14 (7): 407–17PubMedCrossRef
19.
go back to reference Gardiner SJ, Begg EJ. Pharmacogenetic testing for drug metabolizing enzymes: is it happening in practice? Pharmacogenet Genomics 2005; 15: 365–9PubMedCrossRef Gardiner SJ, Begg EJ. Pharmacogenetic testing for drug metabolizing enzymes: is it happening in practice? Pharmacogenet Genomics 2005; 15: 365–9PubMedCrossRef
20.
go back to reference 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 (1210), 1–7 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 (1210), 1–7
21.
go back to reference Weinshilboum RM. Human pharmacogenetics of methyl conjugation. Fed Proc 1984; 43 (8): 2303–7PubMed Weinshilboum RM. Human pharmacogenetics of methyl conjugation. Fed Proc 1984; 43 (8): 2303–7PubMed
22.
go back to reference Gardiner SJ, Gearry RB, Barclay ML, et al. Two cases of thiopurine methyltransferase (TPMT) deficiency: a lucky save and a near miss with azathioprine. Br J Clin Pharmacol. Epub 2005 Aug 1 Gardiner SJ, Gearry RB, Barclay ML, et al. Two cases of thiopurine methyltransferase (TPMT) deficiency: a lucky save and a near miss with azathioprine. Br J Clin Pharmacol. Epub 2005 Aug 1
23.
go back to reference Winter J, Walker A, Shapiro D, et al. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2004; 20: 593–9PubMedCrossRef Winter J, Walker A, Shapiro D, et al. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2004; 20: 593–9PubMedCrossRef
24.
go back to reference Bouhnik Y, Lemann M, Mary J-Y, et al. Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet 1996; 347: 215–9PubMedCrossRef Bouhnik Y, Lemann M, Mary J-Y, et al. Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet 1996; 347: 215–9PubMedCrossRef
25.
go back to reference Chong RY, Hanauer SB, Cohen RD. Efficacy of paraenteral methotrexate in refractory Crohn’s disease. Aliment Pharmacol Ther 2001; 15: 35–44PubMedCrossRef Chong RY, Hanauer SB, Cohen RD. Efficacy of paraenteral methotrexate in refractory Crohn’s disease. Aliment Pharmacol Ther 2001; 15: 35–44PubMedCrossRef
26.
go back to reference Feagan BG, Fedorak RN, Irvine J, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn’s Disease. N Engl J Med 2000; 342: 1627–32PubMedCrossRef Feagan BG, Fedorak RN, Irvine J, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn’s Disease. N Engl J Med 2000; 342: 1627–32PubMedCrossRef
27.
go back to reference Friedman S. General principles of medical therapy of Inflammatory Bowel Disease. Gastroenterol Clin North Am 2004; 33: 191–208PubMedCrossRef Friedman S. General principles of medical therapy of Inflammatory Bowel Disease. Gastroenterol Clin North Am 2004; 33: 191–208PubMedCrossRef
28.
go back to reference Pearson DC, May GR, Fick G, et al. Azathioprine and 6-mercaptopurine in Crohn’s Disease: a meta analysis. Ann Intern Med 1995; 123 (2): 132–42PubMed Pearson DC, May GR, Fick G, et al. Azathioprine and 6-mercaptopurine in Crohn’s Disease: a meta analysis. Ann Intern Med 1995; 123 (2): 132–42PubMed
29.
go back to reference Chong RY, Hanauer SB, Cohen RD. Methotrexate in Crohn’s disease: how’s it doing? [abstract]. Gastroenterology 1998; 114: A951CrossRef Chong RY, Hanauer SB, Cohen RD. Methotrexate in Crohn’s disease: how’s it doing? [abstract]. Gastroenterology 1998; 114: A951CrossRef
30.
go back to reference Bloomfield RS, Onken JE. Mercaptopurine metabolite results in clinical gastroenterology practice. Aliment Pharmacol Ther 2003; 17: 69–73CrossRef Bloomfield RS, Onken JE. Mercaptopurine metabolite results in clinical gastroenterology practice. Aliment Pharmacol Ther 2003; 17: 69–73CrossRef
31.
go back to reference Cunliffe RN, Scott BB. Monitoring for drug side effects in inflammatory bowel disease. Aliment Pharmacol Ther 2002; 16: 647–62PubMedCrossRef Cunliffe RN, Scott BB. Monitoring for drug side effects in inflammatory bowel disease. Aliment Pharmacol Ther 2002; 16: 647–62PubMedCrossRef
32.
go back to reference Schroder O, Stein J. Low dose methotrexate in Inflammatory Bowel Disease: current status and future directions. Am J Gastroenterol 2003; 98 (3): 530–7PubMedCrossRef Schroder O, Stein J. Low dose methotrexate in Inflammatory Bowel Disease: current status and future directions. Am J Gastroenterol 2003; 98 (3): 530–7PubMedCrossRef
33.
go back to reference Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for the maintenance of remission of Crohn’s Disease. Gastroenterology 2000; 118: 1018–24PubMedCrossRef Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for the maintenance of remission of Crohn’s Disease. Gastroenterology 2000; 118: 1018–24PubMedCrossRef
34.
go back to reference Kanik KS, Cash JM. Does methotrexate increase the risk of infection or malignancy? Rheum Dis Clin North Am 1997; 23: 955–67PubMedCrossRef Kanik KS, Cash JM. Does methotrexate increase the risk of infection or malignancy? Rheum Dis Clin North Am 1997; 23: 955–67PubMedCrossRef
35.
go back to reference Present DH, Meltzer SJ, Krumholz MP, et al. 6-Mercaptopurine in the management of inflammatory bowel disease: short and long-term toxicity. Ann Intern Med 1989; 111 (8): 641–9PubMed Present DH, Meltzer SJ, Krumholz MP, et al. 6-Mercaptopurine in the management of inflammatory bowel disease: short and long-term toxicity. Ann Intern Med 1989; 111 (8): 641–9PubMed
36.
go back to reference Egan LJ, Sandborn WJ. Methotrexate for inflammatory bowel disease: pharmacology and preliminary results. Mayo Clin Proc 1996; 71: 69–80PubMedCrossRef Egan LJ, Sandborn WJ. Methotrexate for inflammatory bowel disease: pharmacology and preliminary results. Mayo Clin Proc 1996; 71: 69–80PubMedCrossRef
37.
go back to reference Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32: 651–2PubMed Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32: 651–2PubMed
38.
go back to reference Pharmaceutical Management Agency. Pharmaceutical Schedule [online]. Available from: http://www.pharmac.govt.nz [Accessed 2004 Jul] Pharmaceutical Management Agency. Pharmaceutical Schedule [online]. Available from: http://​www.​pharmac.​govt.​nz [Accessed 2004 Jul]
39.
go back to reference Canterbury Health Laboratories. Canterbury District Health Board. [online]. Available from: http://www.cdhb.govt.nz [Accessed 2004 Jul] Canterbury Health Laboratories. Canterbury District Health Board. [online]. Available from: http://​www.​cdhb.​govt.​nz [Accessed 2004 Jul]
40.
go back to reference Roberts RL, Barclay ML, Gearry RB, et al. A multiplexed allele-specific polymerase chain reaction assay for the detection of common thiopurine S-methyltransferase (TPMT) mutations. Clin Chim Acta 2004; 341: 49–53PubMedCrossRef Roberts RL, Barclay ML, Gearry RB, et al. A multiplexed allele-specific polymerase chain reaction assay for the detection of common thiopurine S-methyltransferase (TPMT) mutations. Clin Chim Acta 2004; 341: 49–53PubMedCrossRef
41.
go back to reference Walmsley TA, Florkowski CM, George PM, et al. Thiopurine methyltransferase: radiochemical microassay and biochemical properties. N Z Med J 2002; 115: 302PubMed Walmsley TA, Florkowski CM, George PM, et al. Thiopurine methyltransferase: radiochemical microassay and biochemical properties. N Z Med J 2002; 115: 302PubMed
42.
go back to reference Weinshilboum RM, Raymond FA, Pazmino PA. Human erythrocyte thiopurine methyl transferase: radiochemical microassay and biochemical properties. Clin Chim Acta 1978; 85: 323–33PubMedCrossRef Weinshilboum RM, Raymond FA, Pazmino PA. Human erythrocyte thiopurine methyl transferase: radiochemical microassay and biochemical properties. Clin Chim Acta 1978; 85: 323–33PubMedCrossRef
43.
go back to reference Devlin NJ, Hansen P, Kind P, et al. The health state preferences and local inconsistencies of New Zealanders: a tale of two tariffs. The University of York, Centre for Health Economics. University of Otago. 2000, Discussion Paper 180 Devlin NJ, Hansen P, Kind P, et al. The health state preferences and local inconsistencies of New Zealanders: a tale of two tariffs. The University of York, Centre for Health Economics. University of Otago. 2000, Discussion Paper 180
44.
go back to reference Weinstein MC, Siegel JE, Gold MR, et al. Recommendation of the panel on cost-effectiveness in health and medicine. JAMA 1996; 276: 1253–8PubMedCrossRef Weinstein MC, Siegel JE, Gold MR, et al. Recommendation of the panel on cost-effectiveness in health and medicine. JAMA 1996; 276: 1253–8PubMedCrossRef
45.
go back to reference Devlin NJ, Hansen P, Kind P, et al. Logical inconsistencies in survey respondents’ health state valuations: a methodological challenge for estimating social tariffs. Health Econ 2003; 12 (7) 529–44PubMedCrossRef Devlin NJ, Hansen P, Kind P, et al. Logical inconsistencies in survey respondents’ health state valuations: a methodological challenge for estimating social tariffs. Health Econ 2003; 12 (7) 529–44PubMedCrossRef
46.
go back to reference EQ-5D [online]. Available from URL: http://www.euroqol.org [Accessed 2006 Jun 22] EQ-5D [online]. Available from URL: http://​www.​euroqol.​org [Accessed 2006 Jun 22]
47.
go back to reference Jowett SL, Seal CJ, Barton JR, et al. The short Inflammatory Bowel Disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gastroenterol 2001; 96: 2921–8PubMedCrossRef Jowett SL, Seal CJ, Barton JR, et al. The short Inflammatory Bowel Disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gastroenterol 2001; 96: 2921–8PubMedCrossRef
48.
go back to reference Oh K-T, Anis AH, Bae S-C. Pharmacoeconomic analysis of thiopurine methyltransferase polymorphism screening by polymerase chain reaction for treatment with azathioprine in Korea. Rheumatology 2004; 43: 156–63PubMedCrossRef Oh K-T, Anis AH, Bae S-C. Pharmacoeconomic analysis of thiopurine methyltransferase polymorphism screening by polymerase chain reaction for treatment with azathioprine in Korea. Rheumatology 2004; 43: 156–63PubMedCrossRef
49.
go back to reference 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: 2507–12PubMed 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: 2507–12PubMed
50.
go back to reference Suarez-Alamazor ME, Spooner C, Belseck E. Azathioprine for treating rheumatoid arthritis. Available in The Cochrane Library [database on disk and CD-ROM]. Updated quaterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2004 Suarez-Alamazor ME, Spooner C, Belseck E. Azathioprine for treating rheumatoid arthritis. Available in The Cochrane Library [database on disk and CD-ROM]. Updated quaterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2004
51.
go back to reference Krynetski EY, Evans WE. Genetic polymorphism of thiopurine S-methyltransferase: molecular rnxhanisms and clinical importance. Pharmacology 2000; 61: 136–46PubMedCrossRef Krynetski EY, Evans WE. Genetic polymorphism of thiopurine S-methyltransferase: molecular rnxhanisms and clinical importance. Pharmacology 2000; 61: 136–46PubMedCrossRef
52.
go back to reference Cheung ST, Allan RN. Mistaken identity: misclassification of TPMT phenotype following blood transfusion. Eur J Gastroenterol Hepatol 2003; 15 (11): 1245–7PubMedCrossRef Cheung ST, Allan RN. Mistaken identity: misclassification of TPMT phenotype following blood transfusion. Eur J Gastroenterol Hepatol 2003; 15 (11): 1245–7PubMedCrossRef
53.
go back to reference Schwab M, Schaeffeler E, Marx C, et al. Shortcoming in the diagnosis of TPMT deficiency in a patient with Crohn’s Disease using phenotyping only. Gastroenterology 2001; 121: 500–1CrossRef Schwab M, Schaeffeler E, Marx C, et al. Shortcoming in the diagnosis of TPMT deficiency in a patient with Crohn’s Disease using phenotyping only. Gastroenterology 2001; 121: 500–1CrossRef
54.
go back to reference Pazmino PA, Sladek SL, Weinshilboum RM. Thiol S-methylation in uremia: erythrocyte enzyme activities and plasma inhibitors. Clin Pharmacol Ther 1980; 28: 356–67PubMedCrossRef Pazmino PA, Sladek SL, Weinshilboum RM. Thiol S-methylation in uremia: erythrocyte enzyme activities and plasma inhibitors. Clin Pharmacol Ther 1980; 28: 356–67PubMedCrossRef
Metadata
Title
Pharmacoeconomic Analyses of Azathioprine, Methotrexate and Prospective Pharmacogenetic Testing for the Management of Inflammatory Bowel Disease
Authors
Virginia L. Priest
Professor Evan J. Begg
Sharon J. Gardiner
Christopher M. A. Frampton
Richard B. Gearry
Murray L. Barclay
David W. J. Clark
Paul Hansen
Publication date
01-08-2006
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 8/2006
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.2165/00019053-200624080-00004

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