The pharmacokinetic effect of adalimumab on thiopurine metabolism in Crohn's disease patients

Journal of Crohn's and Colitis

Volumn 8, Issue 2, 2014, Pages 120-128

  Wong, D R ^a   Pierik, M ^b   Seinen, M L ^c   van Bodegraven, A A ^c   Gilissen, L P L ^d   Bus, P ^e   Bakker, J A ^f   Masclee, A A M ^b   Neef, C ^a,b   Engels, L G J B ^g   Hooymans, P M ^a  

^a Sittard Geleen Heerlen   (Netherlands)

^b MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^d CATHARINA HOSPITAL   (Netherlands)

^e LAURENTIUS HOSPITAL   (Netherlands)

^f LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^g MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

Adalimumab; Azathioprine; Crohn's disease; Drug interaction; Mercaptopurine; Therapeutic drug monitoring

Indexed keywords

6 METHYLTHIOINOSINE; 6 THIOGUANINE NUCLEOTIDE; ADALIMUMAB; AZATHIOPRINE; C REACTIVE PROTEIN; GUANINE DERIVATIVE; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; INORGANIC PYROPHOSPHATASE; INOSINE TRIPHOSPHATE; MERCAPTOPURINE; THIOPURINE METHYLTRANSFERASE; UNCLASSIFIED DRUG;

ADULT; ARTICLE; AUTOIMMUNE THROMBOCYTOPENIA; BONE MARROW TOXICITY; CLINICAL ARTICLE; CROHN DISEASE; CROHN DISEASE ACTIVITY INDEX; DRUG BLOOD LEVEL; DRUG DOSE INCREASE; DRUG METABOLISM; DRUG SAFETY; DRUG WITHDRAWAL; ENZYME ACTIVITY; FEMALE; FOLLOW UP; HUMAN; LEUKOCYTE COUNT; LEUKOPENIA; MAINTENANCE THERAPY; MALE; MIDDLE AGED; PRIORITY JOURNAL; PROSPECTIVE STUDY; THROMBOCYTOPENIA; YOUNG ADULT;

6-METHYLMERCAPTOPURINE RIBONUCLEOTIDES; 6-MMPR; 6-MP; 6-TGN; 6-TGTP; 6-THIOGUANINE NUCLEOTIDES; 6-THIOGUANINE TRIPHOSPHATE; 95% CI; 95% CONFIDENCE INTERVAL; ADALIMUMAB; AZA; AZATHIOPRINE; C-REACTIVE PROTEIN; CD; CDAI; CROHN'S DISEASE; CROHN'S DISEASE ACTIVITY INDEX; CRP; DRUG INTERACTION; HGPRT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HPLC; HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE; IBD; IMP; INFLAMMATORY BOWEL DISEASE; INOSINE MONOPHOSPHATE; INOSINE TRIPHOSPHATE PYROPHOSPHATASE; ITPASE; MCV; MEAN CORPUSCULAR VOLUME; MERCAPTOPURINE; RBC; RED BLOOD CELLS; TDM; THERAPEUTIC DRUG MONITORING; THIOPURINE S-METHYLTRANSFERASE; TPMT; UC; ULCERATIVE COLITIS;

ADOLESCENT; ADULT; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIBODIES, MONOCLONAL, HUMANIZED; AZATHIOPRINE; C-REACTIVE PROTEIN; CROHN DISEASE; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; ERYTHROCYTES; FEMALE; GUANINE NUCLEOTIDES; HUMANS; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; IMMUNOSUPPRESSIVE AGENTS; MALE; METHYLTRANSFERASES; MIDDLE AGED; PROSPECTIVE STUDIES; PYROPHOSPHATASES; SEVERITY OF ILLNESS INDEX; THIOINOSINE; THIONUCLEOTIDES; YOUNG ADULT;

EID: 84892892695     PISSN: 18739946     EISSN: 18764479     Source Type: Journal    
DOI: 10.1016/j.crohns.2013.07.004     Document Type: Article

References (29)

1. Prefontaine E., MacDonald J.K., Sutherland L.R. Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2009, CD000545.
2. Prefontaine E., Sutherland L.R., MacDonald J.K., Cepoiu M. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2009, CD000067.
3. Timmer A., McDonald J.W., MacDonald J.K. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2007, CD000478.
4. Derijks L.J.J., Wong D.R. Pharmacogenetics of thiopurines in inflammatory bowel disease. Curr Pharm Des 2010, 16:145-154.
5. Osterman M.T., Kundu R., Lichtenstein G.R., Lewis J.D. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 2006, 130:1047-1053.
6. Gilissen L.P., Wong D.R., Engels L.G., Bierau J., Bakker J.A., Paulussen A.D., et al. Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy. J Crohns Colitis 2012, 6:698-707.
7. 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.
8. Dubinsky M.C., Lamothe S., Yang H.Y., Targan S.R., Sinnett D., Théorêt Y., et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000, 118:705-713.
9. Haines M.L., Ajlouni Y., Irving P.M., Sparrow M.P., Rose R., Gearry R.B., et al. Clinical usefulness of therapeutic drug monitoring in patients with inadequately controlled inflammatory bowel disease. Inflamm Bowel Dis 2011, 17:1301-1307.
10. Chouchana L., Narjoz C., Beaune P., Loriot M.A., Roblin X. Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2012, 35:15-36.
11. D'Haens G.R., Panaccione R., Higgins P.D., Vermeire S., Gassull M., Chowers Y., et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict responseα Am J Gastroenterol. 2011;106:199-212; quiz 213. Am J Gastroenterol 2011, 106-375. Review. Erratum in.
12. Van Bodegraven A.A., Van Everdingen J.J.E., Dijkstra G., de Jong D.J., Oldenburg B., Hommes D.W. Richtlijn 'Diagnostiek en behandeling van inflammatoire darmziekten bij volwassenen' I. Diagnostiek en behandeling. Ned Tijdschr Geneeskd 2010, 154:A1899.
13. Dignass A., Van Assche G., Lindsay J.O., Lémann M., Söderholm J., Colombel J.F., et al. The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management. J Crohns Colitis 2010, 4:28-62.
14. Colombel J.F., Sandborn W.J., Reinisch W., Mantzaris G.J., Kornbluth A., Rachmilewitz D., et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010, 362:1383-1395.
15. Roblin X., Serre-Debeauvais F., Phelip J.M., Bessard G., Bonaz B. Drug interaction between infliximab and azathioprine in patients with Crohn's disease. Aliment Pharmacol Ther 2003, 18:917-925.
16. Derijks L.J.J., Gilissen L.P.L., Engels L.G.J.B., Bos L.P., Bus P.J., Lohman J.J.H.M., et al. Pharmacokinetics of 6-mercaptopurine in patients with inflammatory bowel disease; implications for therapy. Ther Drug Monit 2004, 26:311-318.
17. De Boer N.K., Wong D.R., Jharap B., de Graaf P., Hooymans P.M., Mulder C.J., et al. Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism. Am J Gastroenterol 2007, 102:1-7.
18. Jacques-Aigrain E., Bessa E., Medard Y., Mircheva Y., Vilmer E. Thiopurine methyltransferase activity in a French population: HPLC assay conditions and effects of drugs and inhibitors. Br J Clin Pharmacol 1994, 38:1-8.
19. Bierau J., Bakker J.A., Lindhout M., van Gennip A.H. Determination of ITPase activity in erythrocyte lysates obtained for determination of TPMT activity. Nucleosides Nucleotides Nucleic Acids 2006, 25:1129-1132.
20. Jacomelli G., Micheli V., Peruzzi L., Notarantonio L., Cerboni B., Sestini S., et al. Simple non-radiochemical HPLC-linked method for screening for purine metabolism disorders using dried blood spot. Clin Chim Acta 2002, 324:135-139.
21. Panaccione R., Ghosh S., Middleton S., Velazquez J., Khalif I., Flint L., et al. Infliximab, azathioprine, or infliximab+azathioprine for treatment of moderate to severe ulcerative colitis: The UC SUCCESS trial. Oral presentation (Abstract OP 13). Presented at the European Crohn's and Colitis Organization (ECCO) Congress, Stockholm September 25 2011.
22. D'Haens G., Baert F., van Assche G., Caenepeel P., Vergauwe P., Tuynman H., et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 2008, 371:660-667.
23. Reenaers C., Louis E., Belaiche J., Seidel L., Keshav S., Travis S. Does co-treatment with immunosuppressors improve outcome in patients with Crohn's disease treated with adalimumabα. Aliment Pharmacol Ther 2012, 36:1040-1048.
24. Teichgräber U., Atreya I., Atreya R., Schwab M., Neurath M.F. Infliximab treatment induces levels of the active azathioprine metabolite 6-TGTP in Crohn's disease. Inflamm Bowel Dis 2013, 19:E54-E55.
25. Neurath M.F., Kiesslich R., Teichgraber U., Fischer C., Hofmann U., Eichelbaum M., et al. 6-Thioguanosine diphosphate and triphosphate levels in red blood cells and response to azathioprine therapy in Crohn's disease. Clin Gastroenterol Hepatol 2005, 3:1007-1014.
26. de Jong D.J., Derijks L.J., Naber A.H., Hooymans P.M., Mulder C.J. Safety of thiopurines in the treatment of inflammatory bowel disease. Scand J Gastroenterol Suppl 2003, 239:69-72.
27. EMA Summary of product characteristics: Humira®, Abbott Laboratories Ltd, United Kingdom; [Internet] Available at:, [Accessed]. http://www.emea.europa.eu/docs/nl_NL/document_library/EPAR_-Product_Information/human/000481/WC500050870.pdf.
28. Gilissen L.P., Bierau J., Derijks L.J., Bos L.P., Hooymans P.M., van Gennip A., et al. The pharmacokinetic effect of discontinuation of mesalazine on mercaptopurine metabolite levels in inflammatory bowel disease patients. Aliment Pharmacol Ther 2005, 22:605-611.
29. de Graaf P., de Boer N.K., Wong D.R., Karner S., Jharap B., Hooymans P.M., et al. Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy. Br J Pharmacol 2010, 160:1083-1091.