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

Introducción: Es necesaria la correcta cuantificación de la actividad inflamatoria de las lesiones de la enfermedad de Crohn para establecer cuál es el tratamiento más adecuado para cada paciente. El objetivo del presente estudio es valorar la relación entre el índice de actividad inflamatorio por resonancia magnética (MaRIA) preoperatorio y el grado de inflamación histológico de las lesiones obtenidas en la cirugía. Métodos: Estudio prospectivo observacional consecutivo que incluye una serie de pacientes con enfermedad de Crohn ileal. Se realizó una enterografía mediante resonancia magnética, con protocolo y secuencias preestablecidas, en los 3 meses previos a la cirugía y se calculó el índice MaRIA. Todos los pacientes fueron intervenidos quirúrgicamente y se remitieron muestras de cada lesión parietal completa a estudio anatomopatológico. En el análisis histológico se empleó la clasificación de Chiorean. Se realizó un análisis de regresión ordinal e intergrupos. Resultados: Se incluye a 35 pacientes con 59 lesiones. A medida que aumenta el grado de inflamación, se obtienen, de forma significativa (p = 0,002), valores mayores de MaRIA. El índice de MaRIA fue considerablemente diferente (p < 0,001) en los diferentes tipo de lesiones por enfermedad de Crohn (inflamatoria/fibrótica). El mejor valor de corte del índice MaRIA para establecer la existencia de inflamación grave en una lesión ha resultado ser 20 (ABC, 0,741; sensibilidad, 74,1%, y especificidad, 78,1%). Conclusiones: En el estudio de la enfermedad de Crohn ileal, la resonancia y el índice MaRIA son herramientas de gran utilidad para diferenciar entre lesiones inflamatorias y fibrosas, y por tanto, imprescindible para decidir el tratamiento más adecuado

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

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.

Actualización en el tratamiento de la colitis ulcerosa / Update on the treatment of ulcerative colitis

En la DDW 2008, en lo referente a la colitis ulcerosa destacaque se han presentado los resultados preliminares de la administraciónde dexametasona encapsulada y administrada enperfusión intravenosa, con resultados muy prometedores eneficacia y seguridad para los pacientes que precisan corticoides.Los datos sobre aminosalicilatos apuntan a las ventajas,porque facilitan una mejor adherencia, de un menor númerode administraciones al día tanto en la inducción de la remisióncomo en el tratamiento de mantenimiento, ya sea en adminitraciónoral o en forma de supositorios. Respecto a los inmunosupresorestiopurínicos, se han aportado datos sobre sufarmacocinética y, especialmente, sobre su perfil de seguridad.Las aportaciones sobre fármacos biológicos, anti-TNF(factor de necrosis tumoral), han sido las derivadas de los subanálisisde los estudios pivotales ACT. Respecto a nuevostratamientos, se han presentado los resultados sobre la eficaciade los probióticos (VSL#3) en la inducción de remisión,asociados a los salicilatos(AU)

The present article reports highlights on the treatment ofulcerative colitis presented at Digestive Disease Week 2008.On the basis of the preliminary results presented, intravenousinfusion of encapsulated dexamethasone may help toimprove outcomes, both in terms of efficacy and toxicity inpatients requiring steroids. Once-daily dosing of 5-ASA/mesalamine is likely to be well received by patientsnow that this dosing regimen appears to be as effective asmultiple daily dosing both in inducing remission and asmaintenance therapy, whether administered orally or as asuppository. New data on the pharmacokinetics and toxicityof immunosuppressive agents and data extracted fromthe pivotal ACT studies (infliximab for ulcerative colitis)were presented. Among the newer agents in the pipeline, aprobiotic preparation (VSL#3) may prove helpful in inducingremission in patients with ulcerative colitis associatedwith 5-ASA(AU)

Corticoides de acción «local» en la enfermedad inflamatoria intestinal. ¿Son eficaces? ¿Son realmente menos tóxicos? / No disponible

No disponible

[Update on the treatment of ulcerative colitis]. / Actualización en el tratamiento de la colitis ulcerosa.

The present article reports highlights on the treatment of ulcerative colitis presented at Digestive Disease Week 2008. On the basis of the preliminary results presented, intravenous infusion of encapsulated dexamethasone may help to improve outcomes, both in terms of efficacy and toxicity in patients requiring steroids. Once-daily dosing of 5-ASA/ mesalamine is likely to be well received by patients now that this dosing regimen appears to be as effective as multiple daily dosing both in inducing remission and as maintenance therapy, whether administered orally or as a suppository. New data on the pharmacokinetics and toxicity of immunosuppressive agents and data extracted from the pivotal ACT studies (infliximab for ulcerative colitis) were presented. Among the newer agents in the pipeline, a probiotic preparation (VSL#3) may prove helpful in inducing remission in patients with ulcerative colitis associated with 5-ASA.

[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.

Nuevos tratamientos y aproximaciones diagnósticas en la colitis ulcerosa / New treatments and diagnostic approaches in ulcerative colitis

La colitis ulcerosa es una enfermedad inflamatoria crónica intestinal que cursa con períodos de exacerbación y remisión y cuyo síntoma fundamental es la rectorragia. El objetivo del tratamiento médico consiste en la inducción de la remisión clínica y su mantenimiento. En el último congreso de la American Gastroenterological Association: Digestive Disease Week (DDW) de 2006 se han presentado nuevos aspectos terapéuticos con respecto a los salicilatos, los estudios ASCEND I y II, que valoran una nueva formulación de mesalazina, y los probióticos. También se han presentado distintos aspectos relacionados con el tratamiento con ciclosporina e infliximab en el brote grave corticorresistente, tales como la respuesta precoz, que es superior con infliximab, y la respuesta tardía, y se han analizado los factores asociados a la posible no respuesta a corticoides. Se han presentado varios estudios analizando la eficacia de la granulocitoaferesis en la colitis ulcerosa, incluso como alternativa a los corticoides (AU)

Ulcerative colitis is a chronic inflammatory bowel disease with periods of flares and remission. The main symptom is rectorrhagia. The aim of medical treatment is to induce and maintain clinical remission. At the last congress of the American Gastroenterological Association: Digestive Diseases Week (DDW) in 2006, new data were presented on salicylates, the ASCEND I&II studies evaluating the new formulation of mesalazine, and prebiotics. Also presented were various findings related to cyclosporin and infliximab therapy in severe steroid-refractory flares, such as an early response – which is greater with infliximab – and late response. The factors associated with the possible lack of response to corticoids were analyzed. Several studies evaluating the efficacy of granulocytapheresis in ulcerative colitis, including its use as an alternative to corticoids, were presented (AU)