Use of magnetic resonance index of activity (MaRIA) in the preoperative assessment of small bowel Crohn's disease. / La resonancia magnética y el índice MaRIA en la valoración preoperatoria de la enfermedad de Crohn ileal.

BACKGROUND: Accurate quantification of the inflammatory activity in Crohn's Disease is essential to determine adequate treatment for each patient. The aim of the present study is to assess the correlation between the pre-operative Magnetic Resonance Index of Activity (MaRIA) and the histologic degree of inflammation from surgically resected intestinal Crohn's Disease lesions. METHODS: This is a prospective study including a consecutive case series of patients with small bowel Crohn's Disease, who underwent surgical resection. Magnetic resonance enterography was performed in the 3months prior to surgery, applying a pre-established protocol. Relative contrast enhancements, wall thickness, presence of edema or ulcerations were the parameters used to calculate the MaRIA Index. All patients underwent surgery and every specimen was analyzed. The modified Chiorean classification was applied for the histological analysis and an ordinal regression analysis was used to correlate MaRIA and the grade of inflammation for each lesion. RESULTS: 59 lesions from 35 different patients were analyzed. The degree of inflammation of the lesions was statistically correlated to the MaRIA values (P=.002). The MaRIA index was significantly different (P<.001) between the different histological types of the Crohn's Disease lesions (inflammatory/ fibrotic). The best cut-off for detecting severe inflammation using MaRIA was 20 (AUC: 0.741; 74.1% sensitivity and 78.1% specificity). CONCLUSION: MaRIA is a reliable tool to distinguish inflammatory from fibrotic lesions. Therefore, it could be considered essential for determining the most appropriate Crohn's Disease treatment for each patient.

Genetic association between CD96 locus and immunogenicity to anti-TNF therapy in Crohn's disease.

The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn's disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e-09). This association was validated in the replication stage (P < 0.05). The risk allele for anti-TNF immunogenicity was found to be also associated with a lack of response to anti-TNF therapy (P = 0.019). These findings represent an important step toward the understanding of the immunogenicity-based mechanisms that underlie anti-TNF response in CD.

A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300.

OBJECTIVE: Genome-wide association studies (GWAS) have identified multiple risk loci for Crohn's disease (CD). However, the cumulative risk exerted by these loci is low, and the likelihood that additional, as-yet undiscovered loci contribute to the risk of CD is very high. We performed a GWAS on a southern European population to identify new CD risk loci. DESIGN: We genotyped 620 901 genome markers on 1341 CD patients and 1518 controls from Spain. The top association signals representing new candidate risk loci were subsequently analysed in an independent replication cohort of 1365 CD patients and 1396 controls. RESULTS: We identified a genome-wide significant association on chromosome 22q13.2 in the intergenic region between the RBX1 and EP300 genes (single nucleotide polymorphism rs4820425, OR 1.27, 95% CI 1.17 to 1.38, p=3.42E-8). We also found suggestive evidence for the association of the IFNGR2 (21q22.11), FOXP2 (7q31), MACROD2 (20p12.1) and AIF1 (6p21.3) loci with CD risk. CONCLUSIONS: In this GWAS performed on a southern European cohort, we have identified a new risk locus for CD between RBX1 and EP300. This study demonstrates that using populations of different ancestry is a useful strategy to identify new risk loci for CD.

[Optimization of immunomodulatory treatment with azathioprine or 6-mercaptopurine in inflammatory bowel disease]. / Optimización del tratamiento inmunomodulador con azatioprina o 6-mercaptopurina en pacientes con enfermedad inflamatoria intestinal.

BACKGROUND: There is limited information on the optimal use of thiopurinic immunomodulators in inflammatory bowel disease (IBD) and the dosage, efficacy and toxicity of these drugs has not been clearly established. AIM: To evaluate clinical outcomes and the toxicity of thiopurinic immunomodulators in clinical practice (effectiveness), as well as possible associated variables. METHODS: Data were obtained from a database of patients with ulcerative colitis and Crohn's disease who started treatment with azathioprine or 6-mercaptopurine with an identical predetermined schedule and follow-up. Remission, relapse and toxicity were defined and analyzed and their relationship with clinical, biologic and demographic variables was evaluated with multivariate analysis. RESULTS: We evaluated 150 courses of treatment in 126 patients. Treatment was given to induce clinical remission in 118 courses and 62% of the patients reached this outcome, which was maintained for a mean of 52 months. The only variable associated with poor response was perianal disease. Adverse events were detected in 34% of the courses and were the main cause of treatment withdrawal. Factors significantly associated with withdrawal due to adverse events were starting with full doses of thiopurinic drugs (OR, 4.26; 95% CI, 1.12-16.32) and cotreatment with infliximab (OR, 5.6; 95% CI, 1.17-27.1). CONCLUSIONS: Some clinical variables such as disease phenotype, the use of full doses of thiopurinic drugs from the start of treatment, and co-treatments can have a notable influence on adverse effects and thus on the effectiveness of this therapy in IBD.