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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 6/2010

01-06-2010 | Original Article

Response to Medical Treatment in Patients with Crohn’s Disease: The Role of NOD2/CRAD15, Disease Phenotype, and Age of Diagnosis

Authors: B. Weiss, O. Lebowitz, H. H. Fidder, I. Maza, A. Levine, R. Shaoul, S. Reif, Y. Bujanover, A. Karban

Published in: Digestive Diseases and Sciences | Issue 6/2010

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Abstract

Purpose

Factors influencing response to medications in Crohn’s disease (CD) patients are not fully understood. We aimed to evaluate the relationships between NOD2/CARD15 mutations, disease phenotype and age of CD diagnosis and response to medical treatment with systemic steroids, azathioprine (AZA) or 6-mercaptopurine (6-MP), and infliximab.

Methods

A retrospective medical records analysis was made of patients previously tested for the CD-associated NOD2/CARD15 mutations. Harvey- Bradshaw score was used to assess remission or response to therapy.

Results

CD-associated NOD2/CARD15 mutations were not related to the rate of steroids dependency or clinical response to AZA/6-MP and infliximab. Steroid dependency was associated with colonic involvement. Thirty-three of 127 (26%) patients with colonic disease were steroid dependent, compared with 7/72 (9.7%) patients with isolated small bowel disease (ISBD), (p = 0.009). ISBD was mildly associated with a better remission/response to AZA/6-MP treatment. Disease behavior and age of diagnosis were not related to response to therapy.

Conclusions

Response to treatment with systemic steroids, AZA/6-MP and infliximab are not related to NOD2/CARD15 mutations, age of diagnosis and disease behavior. Patients with colonic disease have higher rates of steroid dependency.
Literature
1.
Vader JP, Froehlich F, Juillerat P, et al. Appropriate treatment for Cohn’s disease: Methodology and summary results of a multidisciplinary international expert panel approach-EPACT. Digestion. 2006;73:237–248.CrossRefPubMed
2.
Travis SPL, Stange EF, Lémann M, Öresland T, Chowers Y, Forbes A, D’Haens G, Kitis G, Cortot A, Prantera C, Marteau P, Colombel J-F, Gionchetti P, Bouhnik Y, Tiret E, Kroesen J, Starlinger M, Mortensen NJ for the European Crohn’s and Colitis Organisation (ECCO). European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. Gut. 2006;55(Suppl 1):i16–i35.
3.
Escher JC, Jan A, Taminiau JM, et al. Treatment of inflammatory bowel disease in childhood: Best available evidence. Inflamm Bowel Dis. 2003;9:34–58.CrossRefPubMed
4.
Munkholm P, Langholz E, Davidsen M, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn’s disease. Gut. 1994;35:360–362.CrossRefPubMed
5.
Faubion WA Jr, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of corticosteroid therapy for inflammatory bowel disease: A population-based study. Gastroeneterolgy. 2001;121:255–260.CrossRef
6.
Reinish W, Volgelsang H. Steroid dependency in Crohn’s disease. Gastroenterolgy. 2002;123:393–394.CrossRef
7.
Markowitz J, Hyams J, Mack D, et al. Corticosteroid therapy in the age of infliximab: Acute and 1-year outcomes in newly diagnosed children with Crohn’s disease. Clin Gastroentrol Hepatol. 2006;4:1124–1129.CrossRef
8.
Teml A, Schaeffeler E, Herrlinger KR, Klotz U, Schwab M. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing. Clin Pharmacokinet. 2007;46:187–208.CrossRefPubMed
9.
Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132:863–873.CrossRefPubMed
10.
Hanauer SB, Feagan PG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet. 2002;359(9317):1541–1549.CrossRefPubMed
11.
Kappelman M, Bousvaros A, Hyams J, et al. Intercenter variation in initial management of children with Crohn’s disease. Inflamm Bowel Dis. 2007;13:890–895.CrossRefPubMed
12.
Weiss B, Shamir R, Bujanover Y, et al. NOD2/CARD15 mutation analysis and genotype-phenotype correlation in Jewish pediatric patients compared to adults with Crohn’s disease. J Pediatr. 2004;145:208–212.CrossRefPubMed
13.
Karban A, Waterman M, Panhuysen CT, et al. NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic jews with Crohn’s disease. Am J Gastroenterol. 2004;99:1134–1140.CrossRefPubMed
14.
Fidder HH, Olschwang S, Avidan B, et al. Association between mutations in the CARD15 (NOD2) gene and Crohn’s disease in Israeli Jewish patients. Am J Med Genet. 2003;121A:240–244.CrossRefPubMed
15.
Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19(Suppl A):5–36.PubMed
16.
17.
Walkiewicz D, Werlin SL, Fish D, Scanlon M, Hanaway P, Kugathasan S. Fecal calprotectin is useful in predicting disease relapse in pediatrix inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:669–673.CrossRefPubMed
18.
Walker TR, Land ML, Kartashov A, et al. Fecal lactoferrin is a sensitive and specific marker of disease activity in children and young adults with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;44:414–422.CrossRefPubMed
19.
Dixon WJ. BMDP statistical software. Los-Angeles: University of California Press, 1993.
20.
Cucchiara S, Latiano A, Palmieri O, et al. on behalf of the Italian Society of Pediatric Gastroenterology and Nutrition. Polymorphisms of tumor necrosis factor-alpha but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;44:171–179.CrossRefPubMed
21.
Towers R, Naftali T, Gabay G, Carlebach M, Klein A, Novis B. High levels of glucocorticoid receptors in patients with active Crohn’s disease may predict steroid resistance. Clin Exp Immunol. 2005;141:357–362.CrossRefPubMed
22.
Dubinski MC, Huiying Y, Hassard PV, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology. 2002;122:904–915.CrossRef
23.
Tiede I, Fritz G, Strans S, et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest. 2003;111:1133–1145.PubMed
24.
Vermeire S, Louis E, Rutgeerts P, et al. NOD2/CARD15 does not influence response to infliximab in Crohn’s disease. Gastroenterology. 2002;123:106–111.CrossRefPubMed
25.
Urcelay E, Mendoza JL, Martinez A, et al. IBD5 polymorphisms in inflammatory bowel disease: Association with response to infliximab. World J Gastroenterol. 2005;11:1187–1192.PubMed
26.
Matsukura H, Ikeda S, Yoshimura N, Takazoe M, Muramatsu M. Genetic polymorphisms of TNF receptor superfamily 1A and 1B (TNFRSF1A and TNFRCF1B) affect responses to infliximab in Crohn’s disease patients in Japan. Aliment Pharmacol Ther. 2008;27:765–770.PubMedCrossRef
27.
Sandborn WJ, Feagan BG, Lichtenstein GR. Medical management of mild to moderate Crohn’s disease: evidence-based treatment algorithms for induction and maintenance of remission. Aliment Pharmacol Ther. 2007;26:987–1003.CrossRefPubMed
28.
Franchimont DP, Louis E, Croes F, et al. Clinical pattern of corticoid dependent Crohn’s disease. Eur J Gastroenterol Hepatol. 1998;10:821–825.CrossRefPubMed
29.
Polito JM, Childs B, Mellits ED, Tokayer AZ, Harris ML, Bayless TM. Crohn’s disease: Influence of age at diagnosis on site and clinical type of disease. Gastroenterology. 1996;111:580–586.CrossRefPubMed
30.
Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. Guidelines for the management of growth failure in childhood inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:839–849.CrossRefPubMed
Metadata
Title
Response to Medical Treatment in Patients with Crohn’s Disease: The Role of NOD2/CRAD15, Disease Phenotype, and Age of Diagnosis
Authors
B. Weiss
O. Lebowitz
H. H. Fidder
I. Maza
A. Levine
R. Shaoul
S. Reif
Y. Bujanover
A. Karban
Publication date
01-06-2010
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 6/2010
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-009-0936-8

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