TORNA ALL’ELENCO

Relationship between NOD2/CARD15 gene polymorphisms and response to anti-TNF agents in inflammatory bowel diseases: Results of a clinical cohort study in Digestive and Liver Disease

2012
AO Ordine Mauriziano

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (13)Vedi tutti...

Arese D

Sambataro A

Simondi D


et alii...

Abstract

Background and aim: Crohn's Disease (CD) and Ulcerative Colitis (UC) are intestinal diseases of unknown etiology. NOD2/CARD15 gene polymorphisms are associated with CD and with stricturing/fistulizing disease, early onset, ileal localization. Anti-TNF agents have demonstrated good effectiveness in CD and UC, but only65% of patients achieve a satisfactory clinical response. Our main purpose was to correlate NOD2/CARD15 mutations with the response to anti-TNF therapy. Material and methods:79 CD and UC patients treated with inflixmab or adalimumab for at least25 weeks were retrospectively recruited from 3 gastroenterological centers in Turin. A blood sample was obtained to assess most frequent NOD2/CARD15 mutations (R702W, G908R,1007fs). The response to therapy was assessed by clinical parameters (CDAI index). Results:79 patients (42 males and 37 females), with mean age of43.9 years were recruited, 53 with CD (67%) and26 with UC (33%). 59 patients (75%) were treated with infliximab and20 (25%) with adalimumab.22 patients (28%) showed anyone of NOD2/CARD15 mutations, with a correlation between CD and NOD2/CARD15 polymorphisms (OR4.28, p=0.04). Among CD patients, 5 (9%) had G908R,7 (13%) L1007fs and7 (13%) R702W variant. Among UC subjects, 3 (11%) patients had R702W mutation. In49 patients (62%), a clinical response to anti TNF-alpha was observed. CD diagnosis was associated with better clinical response (OR2.29, p=0.06, IC 0.93-9.08) and the presence of any NOD2/CARD15 polymorphism decreased the rate of clinical response of about70% (OR 0.30, p=0.05, IC 0.09-1.02). In CD, female gender was associated to more favorable response (OR4.09, p=0.04, IC1.09-15.46). In UC patients, genetic polymorphisms were not associated with clinical and endoscopic outcome. Conclusions: Polymorphisms of NOD2/CARD15 play a role in long-term response to biologic drugs in CD patients. We could not demonstrate an association between specific SNPs and the response to therapy. There is not

DOI : 10.1016/S1590-8658(12)60327-2

Keywords

tumor necrosis factor inhibitor; adalimumab; tumor necrosis factor; infliximab; gastrointestinal disease; DNA polymorphism; enteritis; cohort analysis; health care organization; human; patient; mutation; therapy; female; ulcerative colitis; genetic polymorphism; diagnosis; blood sampling; etiology; enteropathy; gender; male; parameters; gene; Crohn disease;