Thiopurine treatment in inflammatory bowel disease: Response predictors, safety, and withdrawal in follow-up

Journal of Crohn's and Colitis

Volumn 6, Issue 5, 2012, Pages 588-596

  Costantino, Giuseppe ^a   Furfaro, Federica ^a   Belvedere, Alessandra ^a   Alibrandi, Angela ^a   Fries, Walter ^a  

^a UNIVERSITY OF MESSINA   (Italy)

Author keywords

6 mercaptopurine; 6 MMP; 6 TGN; Azathioprine; Safety; TPMT

Indexed keywords

C REACTIVE PROTEIN; MERCAPTOPURINE;

ABDOMINAL PAIN; ADULT; ANEMIA; ARTICLE; BONE MARROW TOXICITY; CROHN DISEASE; CYTOMEGALOVIRUS INFECTION; DISEASE DURATION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; ERYTHROCYTE SEDIMENTATION RATE; FEMALE; FLU LIKE SYNDROME; FOLLOW UP; HERPES SIMPLEX KERATITIS; HERPES ZOSTER; HUMAN; LEUKOPENIA; LISTERIOSIS; LIVER FUNCTION TEST; LIVER TOXICITY; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; MONOTHERAPY; MYCOPLASMA PNEUMONIA; NAUSEA; PANCOLITIS; PREDICTOR VARIABLE; PRIORITY JOURNAL; RECEIVER OPERATING CHARACTERISTIC; RETROSPECTIVE STUDY; SIDE EFFECT; TREATMENT RESPONSE; ULCERATIVE COLITIS; VAGINITIS; VOMITING;

6-MERCAPTOPURINE; ADOLESCENT; ADULT; AGED; AZATHIOPRINE; CHILD; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FOLLOW-UP STUDIES; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATORY BOWEL DISEASES; MALE; MIDDLE AGED; PATIENT COMPLIANCE; PATIENT SAFETY; RETROSPECTIVE STUDIES; ROC CURVE; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84860837896     PISSN: 18739946     EISSN: 18764479     Source Type: Journal    
DOI: 10.1016/j.crohns.2011.11.007     Document Type: Article

References (49)

1. Sandborn W.J., Sutherland L., Pearson D., May G., Modigliani R., Prantera C. Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease. Cochrane Database Syst Rev 2000, 2:CD000545.
2. Pearson D.C., May G.R., Fick G., Sutherland L.R. Azathioprine for maintaining remission of Crohn's disease. Cochrane Database Syst Rev 2000, 2:CD000067.
3. Khan K.J., Dubinsky M.C., Ford A.C., Ullman T.A., Talley N.J., Moayyedi P. Efficacy of immunosuppressive therapy for inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 2011, 106:630-642.
4. Ramadas A.V., Gunesh S., Thomas G.A., Williams G.T., Hawthorne A.B. Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates. Gut 2010, 59:1200-1206.
5. Bastida G., Nos P., Aguas M., Beltrán B., Iborra M., Ortiz V., et al. The effects of thiopurine therapy on health-related quality of life in inflammatory bowel disease patients. BMC Gastroenterol 2010, 10:26.
6. Jharap B., Seinen M.L., de Boer N.K., van Ginkel J.R., Linskens R.K., Kneppelhout J.C., et al. Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year intercept cohorts. Inflamm Bowel Dis 2010, 16:1541-1549.
7. Fraser A.G., Orchard T.R., Jewell D.P. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 years review. Gut 2002, 50:485-489.
8. Nielsen O.H., Vainer B., Rask-Madsen J. Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine. Aliment Pharmacol Ther 2001, 15:1699-1708.
9. Al Hadithy A.F.Y., de Boer N.K.H., Derijks L.J.J., Escher J.C., Mulder C.J., Brouwers J.R. Thiopurines in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring and clinical recommendations. Dig Liver Dis 2005, 37:282-297.
10. Connel W.R., Kamm M.A., Ritchie J.K., Lennard-Jones J.E. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27years of experience. Gut 1993, 34:1081-1085.
11. Colonna T., Korelitz B.I. The role of leukopenia in the 6-mercaptopurine induced remission of refractory Crohn's disease. Am J Gastroenterol 1994, 89:362-366.
12. Achkar J.P., Stevens T., Easley K., Brzezinski A., Seidner D., Lashner B. Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease. Inflamm Bowel Dis 2004, 10:339-345.
13. Decaux G., Prospert F., Hormans Y., Desager J.P. Relationship between red cell mean corpuscular volume and 6-thioguanine nucleotides in patients treated with azathioprine. J Lab Clin Med 2000, 135:256-262.
14. D'Halluin P.N., Tribut O., Branger B., Lebreton C., Bretagne J.F., Bentue-Ferrer D., et al. RBC 6-TGN and hematological parameters in patients with Crohn's disease treated by azathioprine. Gastroenterol Clin Biol 2005, 29:1264-1269.
15. Cuffari C., Théorêt Y., Latour S., Seidman G. 6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. Gut 1996, 39:401-406.
16. Wright S., Sanders D.S., Lobo A.J., Lennard L. Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease. Gut 2004, 53:1123-1128.
17. Gardiner S.J., Gearry R.B., Begg E.J., Zhang M., Barclay M.L. Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold. Clin Gastroenterol Hepatol 2008, 6:654-660.
18. Derijks L.J.J., Gilissen L.P.L., Hooymans P.M., Hommes D.W. Review article: thiopurines in inflammatory bowel disease. Aliment Pharmacol Ther 2006, 24:715-729.
19. Colombel J.F., Ferrari N., Debuysere H., Marteau P., Gendre J.P., Bonaz B., 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.
20. Sayani F.A., Prosser C., Bailey R.J., Jacobs P., Fedorak R.N. Thiopurine methyltransferase enzyme activity determination before treatment of inflammatory bowel disease with azathioprine: effect on cost and adverse events. Can J Gastroenterol 2005, 19:147-151.
21. Roblin X., Oussalah A., Chevaux J.B., Sparrow M., Peyrin-Biroulet L. Use of thiopurine testing in the management of inflammatory bowel diseases in clinical practice: a worldwide survey of experts. Inflamm Bowel Dis 2011, 17:2480-2487. 10.1002/ibd.21662.
22. Mowat C., Cole A., Windsor A., Ahmad T., Arnott I., Driscoll R., et al. IBD Section of the British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011, 60:571-607.
23. Lichtenstein G.R., Hanauer S.B., Sandborn W.J. Practice Parameters Committee of American College of Gastroenterology. Management of Crohn's disease in adults. Am J Gastroenterol 2009, 104:465-483.
24. Satsangi J., Silverberg M.S., Vermeire S., Colombel J.F. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006, 55:749-753.
25. Dignass A., Van Assche A., Lindsay J.O., Lémann M., Söderholm J., Colombel J.F., et al. European Crohn's and Colitis Organisation (ECCO). The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management. J Crohn's Colitis 2010, 4:28-62.
26. Travis S.P.L., Stange E.F., Lémann M., Øresland T., Bemelman W.A., Chowers Y., et al. M. Gassull for the European Crohn's and Colitis Organisation (ECCO). European evidence-based Consensus on the management of ulcerative colitis: current management. J Crohn's Colitis 2008, 2:24-62.
27. Chebli J.M., Gaburri P.D., De Souza A.F., Pinto A.L., Chebli L.A., Felga G.E., et al. Long-term results with azathioprine therapy in patients with corticosteroid-dependent Crohn's disease: open-label prospective study. J Gastroenterol Hepatol 2007, 22:268-274.
28. Komiyama T., Yajima T., Kubota R., Iwao Y., Sakuraba A., Funakoshi S., et al. Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese IBD patients. J Crohn's Colitis 2008, 2:315-321.
29. Gisbert J.P., Niño P., Cara C., Rodrigo L. Comparative effectiveness of azathioprine in Crohn's disease and ulcerative colitis: prospective, long-term, follow-up study of 394 patients. Aliment Pharmacol Ther 2008, 28:228-238.
30. Thia K.T., Li M., Ling K.L., Ooi C.J. Azathioprine is effective in corticosteroid-dependent Asian inflammatory bowel disease patients. Inflamm Bowel Dis 2011, 17:809-815.
31. Decaux G., Prospert F., Horsmans Y., Desager J.P. Relationship between red cell mean corpuscular volume and 6-thioguanine nucleotides in patients treated with azathioprine. J Lab Clin Med 2000, 135:256-262.
32. Thomas C.W., Lowry P.W., Franklin C.L., Weaver A.L., Myhre G.M., Mays D.C., et al. Erythrocyte mean corpuscular volume as a surrogate marker for 6-thioguanine nucleotide concentration monitoring in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Inflamm Bowel Dis 2003, 9:237-245.
33. Lowry P.W., Franklin C.L., Weaver A.L., Pike M.G., Mays D.C., Tremaine W.J., et al. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut 2001, 49:665-670.
34. Belaiche J., Desager J.P., Horsmans Y., Louis E. Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease. Scand J Gastroenterol 2001, 36:71-76.
35. Kwan L.Y., Devlin S.M., Mirocha J.M., Papadakis K.A. Thiopurine methyltransferase activity combined with 6-thioguanine metabolite levels predicts clinical response to thiopurines in patients with inflammatory bowel disease. Dig Liver Dis 2008, 40:425-432.
36. González-Lama Y., Bermejo F., López-Sanromán A., García-Sánchez V., Esteve M., Cabriada J.L., et al. Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients. Aliment Pharmacol Ther 2011, 34:544-554.
37. Lopez-Sanroman A., Bermejo F., Carrera E., Garcia-Plaza A. Efficacy and safety of thiopurinic immunomodulators (azathioprine and mercaptopurine) in steroid-dependent ulcerative colitis. Aliment Pharmacol Ther 2004, 20:161-166.
38. Solem C.A., Loftus E.V., Tremaine W.J., Harmsen W.S., Zinsmeister A.R., Sandborn W.J. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis 2005, 11:707-712.
39. Turner D., Mack D.R., Hyams J., LeLeiko N., Otley A., Markowitz J., et al. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) or both? A systematic evaluation in pediatric ulcerative colitis. J Crohn's Colitis 2011, 5:423-429. 10.1016/j.crohns.2011.05.003.
40. Holtmann M.H., Krummenauer F., Claas C., Kremeyer K., Lorenz D., Rainer O., et al. Significant differences between Crohn's disease and ulcerative colitis regarding the impact of body mass index and initial disease activity on responsiveness to azathioprine: results from a European multicenter study in 1,176 patients. Dig Dis Sci 2010, 55:1066-1078.
41. Weiss B., Lebowitz O., Fidder H.H., Maza I., Levine A., Shaoul R., et al. Response to medical treatment in patients with Crohn's disease: the role of NOD2/CARD15, disease phenotype, and age of diagnosis. Dig Dis Sci 2010, 55:1674-1680.
42. Saibeni S., Virgilio T., D'Incà R., Spina L., Bortoli A., Paccagnella M., et al. The use of thiopurines for the treatment of inflammatory bowel diseases in clinical practice. Dig Liver Dis 2008, 40:814-820.
43. Markowitz J., Grancher K., Kohn N., Lesser M., Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology 2000, 119:895-902.
44. Yip J.S., Woodward M., Abreu M.T., Sparrow M.P. How are azathioprine and 6-mercaptopurine dosed by gastroenterologists? Results of a survey of clinical practice. Inflamm Bowel Dis 2008, 14:514-518.
45. Hindorf U., Lindqvist M., Hildebrand H., Fagerberg U., Almer S. Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease. Aliment Pharmacol Ther 2006, 24:331-342.
46. Lewis J.D., Abramson O., Pascua M., Liu L., Asakura L.M., Velayos F.S., et al. Timing of myelosuppression during thiopurine therapy for inflammatory bowel disease: implications for monitoring recommendations. Clin Gastroenterol Hepatol 2009, 7:1195-1201.
47. Lo Presti M.A., Cascio A., della Torre A., Belvedere A., Cascio A., Fries W. Severe CMV-related pneumonia complicated by the hemophagocytic lymphohistiocytic (HLH) syndrome in quiescent Crohn's colitis - harmful cure?. Inflamm Bowel Dis 2011, 17:E145-E146. 10.1002/ibd.21828.
48. Lichtenstein G.R., Abreu M.T., Cohen R., Tremaine W. American Gastroenterological Association. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006, 130:935-939.
49. Aberra F.N., Lichtenstein G.R. Review article: monitoring of immunomodulators in inflammatory bowel disease. Aliment Pharmacol Ther 2005, 21:307-319.