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Background: It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated. Aim: To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor. Methods: We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 ± 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs). Results: Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up ( P < 0.05). Ileal resection was the only variable independently associated with CARD15 variants at multivariate analysis (OR 3.8; 95% CI 1.6–9.2; P = 0.003). Kaplan–Meier analysis showed that ileal resection was favoured both by CARD15 variant-carriage ( P = 0.01) and by smoking ( P = 0.05), but smoking did not affect progression to surgery in variant carriers ( P = 0.31). Thirteen of 14 (93%) patients being resection-free at 15-year follow-up, had CARD15 wild-type genotype ( P = 0.01), whereas only seven (50%) had never smoked ( P = 1.0). Conclusions: In summary, CARD15 variant-associated Crohn's ileitis is virtually committed to stricturing and/or penetrating disease and, eventually, to resective surgery. Smoking accelerates progression to surgery in patients with wild-type CARD15 genotype, but it seems to exert no additional effect in CARD15-variant carriers. [ABSTRACT FROM AUTHOR]

Background: Recent data indicate that 5-aminosalicylic acid (5-ASA) is most effective in preventing relapse of Crohn's disease in patients with a short duration of remission before enrollment., Aim: To evaluate the efficacy of oral 5-ASA treatment, started immediately after achieving steroid-induced remission, in preventing clinical relapses of Crohn's disease., Methods: Patients with active Crohn's disease, achieving remission on steroids, were randomized to oral 5-ASA 3 g/day or placebo, while steroids were tapered over 6 weeks. The trial was terminated after interim analysis showed a slightly higher relapse rate in the 5-ASA group, and the calculated probability of seeing a statistically significant difference by completing the study was minimal., Results: Final analysis included 117 patients (58 taking 5-ASA and 59 taking placebo; follow-up 9.2 +/- 6.5 months). Cumulative relapse rates at 6 and 12 months were 34% and 58% in 5-ASA patients and 31% and 52% in placebo patients, respectively (rate difference +0.095; 95% CI = -0.085 to +0.274). Subgroups analysis showed that 5-ASA was equally ineffective in patients with ileal, colonic or ileocolonic disease., Conclusions: Contrary to previous results, in our study early introduction of treatment with oral 5-ASA did not prevent relapse in Crohn's disease patients treated with steroids to induce remission.