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Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn’s disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.

Malaltia de Crohn; Factors predictius; Ustekinumab Enfermedad de Crohn; Factores predictivos; Ustekinumab Crohn’s disease; Predictive factors; Ustekinumab Ustekinumab has shown efficacy in Crohn’s Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients’ data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission. This work was supported by Janssen-Cilag Spain. This sponsor had a partial role in study design, analysis, and interpretation of data.

Background Data on the long-term administration of ustekinumab in recommended doses are limited. Aim To assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn's disease (CD). Methods Multicenter study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey-Bradshaw Index (HBI), endoscopic activity, C-reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined. Results A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti-TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission. Conclusion After 52 weeks, ustekinumab demonstrated effectiveness to induce clinical and endoscopic remission with safety in patients with refractory CD.

This is the peer reviewed version of the following article: Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents. Journal of Gastroenterology and Hepatology (2020): 29 April, which has been published in final form at https://doi.org/10.1111/jgh.15084. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions, Biological therapies may be changing the natural history of inflammatory bowel diseases, reducing the need for surgical intervention. We aimed to assess whether the availability of anti‐TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). Methods Retrospective, cohort study of patients diagnosed within a 6‐year period before and after the licensing of anti‐TNFs (1990‐1995 and 2007‐2012 for CD; 1995‐2000 and 2007‐2012 for UC) were identified in the ENEIDA Registry. Surgery‐free survival curves were compared between cohorts. Results A total of 7,370 CD patients (2,022 in Cohort 1 and 5,348 in Cohort 2) and 8,069 UC patients (2,938 in Cohort 1 and 5,131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post‐biological cohorts. The cumulative probability of surgery was lower in CD following anti‐TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3 and 5 years, respectively p

Resumen Introduccion El deficit de hierro sin anemia asociada (DHSA) es un hallazgo frecuente en los pacientes no ingresados con enfermedad inflamatoria intestinal (EII), incluso en mayor proporcion que la anemia. Sin embargo, no existen datos concluyentes de su presencia en nuestro medio ni del posible deterioro que conlleva en la calidad de vida relacionada con la salud (CVRS). Los objetivos de este trabajo fueron: establecer la prevalencia del DHSA, identificar posibles factores asociados y medir su impacto en la CVRS. Material y metodos Se incluyeron 127 pacientes con EII, de manera consecutiva, en medio extrahospitalario en un estudio observacional, descriptivo, de corte transversal. Se definio DHSA como niveles de ferritina ≤30 ng/ml en ausencia de actividad inflamatoria o Resultados La prevalencia del DHSA fue del 37%. El sexo femenino (OR = 2,9; p = 0,015) y la presencia de actividad inflamatoria (OR = 9,4; p = 0,001) fueron las variables asociadas con su aparicion. Los pacientes con DHSA presentaron cuestionarios de CVRS con menores puntuaciones de forma global; registrando una caida de 6,6 (p Conclusion La prevalencia de DHSA es considerable en los pacientes con EII en el ambito extrahospitalario. Se asocia al sexo femenino y a la actividad inflamatoria, y supone un claro impacto negativo en la CVRS. Es necesaria una actitud mas activa para el tratamiento de esta complicacion.

Resumen Introduccion y objetivo Infliximab biosimilar (CT-P13) ha sido aprobado para las mismas indicaciones que infliximab original (Remicade ® ); sin embargo, hay pocos datos clinicos sobre el intercambio en la enfermedad inflamatoria intestinal (EII). El objetivo del estudio fue evaluar la eficacia, la seguridad, el perfil de biodisponibilidad y los factores asociados a la recidiva tras el intercambio a infliximab biosimilar en pacientes con EII en remision clinica. Material y metodos Estudio observacional con pacientes con EII tratados con Remicade ® durante al menos 6 meses y en remision clinica durante al menos 3 meses, a los que se realizo el intercambio a infliximab biosimilar. Se evaluo la incidencia de recidiva, los efectos adversos y los cambios en la biodisponibilidad del farmaco (niveles y anticuerpos). Resultados Se incluyeron 36 pacientes (63,9% EC), con una media de seguimiento de 8,4 meses (± 3,5). El 13,9% presentaron recidiva clinica. El mayor tiempo de remision clinica previo al intercambio (HR = 0,54; IC 95% = 0,29-0,98; p = 0,04) y niveles de infliximab detectables en el momento del intercambio (HR = 0,03; IC 95% = 0,001-0,89; p = 0,04) se asociaron a menor riesgo de recidiva. No hubo diferencias entre niveles de infliximab en el momento del intercambio y en las semanas 8 y 16 (p = 0,94). El 8,3% presentaron algun efecto adverso, requiriendo suspension del farmaco en un paciente por neumonia grave. Conclusion El intercambio a infliximab biosimilar en una cohorte de vida real de pacientes con EII en remision clinica no parece tener un impacto significativo en los resultados clinicos a corto plazo. Los factores asociados con la recidiva fueron similares a los esperados en pacientes que continuan con Remicade ® .

INTRODUCTION: To compare Engerix-B and Fendrix hepatitisBvirus for primo vaccination in inflammatory bowel disease (IBD). METHODS: Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs >= 100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS: A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs >= 100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P 5 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in13% of patients after 6months and 20% after12months. Anti-HBs 100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION: We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs

INTRODUCTION: Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR. METHODS: Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively. RESULTS: A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis. DISCUSSION: In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.

espanolIntroduccion y objetivo: la enfermedad de Crohn (EC) es una de las entidades que constituyen la enfermedad inflamatoria intestinal. Sus sintomas principales son la diarrea y el dolor abdominal. El objetivo de nuestro estudio es analizar la utilidad de 75SeHCAT en pacientes con EC que presentan diarrea cronica, con sospecha de malabsorcion de acidos biliares (MAB), y establecer si existe relacion con las caracteristicas de la enfermedad y la reseccion intestinal. Pacientes y metodo: se realizo un estudio observacional transversal a 39 pacientes con diagnostico de EC y diarrea cronica. A todos se les realizo una gammagrafia con 75SeHCAT para el diagnostico de MAB, tras descartar actividad de la enfermedad. Resultados: se analizo un total de 19 mujeres y 20 hombres con una mediana de edad de 44 anos y con una clasificacion de Montreal A2 L1 B1 en el mayor porcentaje. El 84,6% de los pacientes presentaban antecedentes de reseccion intestinal. El porcentaje global de MAB fue del 97,4% (el 100% de los pacientes intervenidos y el 83,3% de los pacientes no intervenidos), y esta fue grave en el 92,1% de los casos. Se establecio tratamiento con quelantes de acidos biliares, que obtuvo una respuesta del 72,7%. Se analizo la existencia de una posible relacion entre las caracteristicas de la enfermedad y de la cirugia intestinal y la respuesta al tratamiento con quelantes con el grado de MAB que presentaban los pacientes (moderada o grave). El resultado obtenido fue no significativo. Conclusion: la MAB es una causa muy frecuente de diarrea en pacientes con EC en remision endoscopica o radiologica, estando presente en todos los pacientes analizados con reseccion intestinal previa. La respuesta al tratamiento con quelantes de acidos biliares estuvo presente en el 73% de los pacientes. EnglishIntroduction and aim: Crohn’s disease (CD) is a form of inflammatory bowel disease and is mainly characterized by diarrhea and abdominal pain. The aim of our study was to analyze the usefulness of performing a 75SeHCAT scan in CD patients with chronic diarrhea and suspected bile acid malabsorption (BAM). In addition, we aimed to determine whether there was a relationship with the clinical features of the disease and a previous bowel resection. Patients and methods: this was an observational cross-sectional study of 39 patients with a diagnosis of CD and chronic diarrhea. All cases underwent a 75SeHCAT scan for BAM diagnosis, after discarding disease activity. Results: the study cohort included 19 females and 20 males. The median age was 44 years and the majority of patients were A2 L1 B1 according to the Montreal classification; 84.6% of patients had undergone a previous bowel resection. BAM was present in 97.4% of patients (100% and 83.3% of patients with and without previous surgery, respectively), which was severe in 92.1% of cases. Treatment with bile acid sequestrants was initiated and a favorable response was obtained in 72.2% of patients. The relationship between BAM degree (moderate or severe), bowel surgery and the response to bile acid sequestrant treatment was also analyzed but not statistically significant. Conclusion: BAM is a frequent cause of diarrhea in CD patients in endoscopic or radiological remission. This condition was present in all patients with a history of a bowel resection. A response to bile acid sequestrants treatment was observed in 73% of patients.

Background: Peculiarities of inflammatory bowel disease (IBD) have been explored in ethnic groups, such as Asians, Hispanics, and Afro-Americans, but not in other ethnic minorities, such as Roma/Gypsies. Methods: In a retrospective, hospital-based study, all adult Roma/Gypsy patients included in the IBD databases of seven Spanish centres were identified as cases. For each Roma/Gypsy patient, a Caucasian patient, matched for several demographic features, was searched as a control. Data on phenotypic features, therapeutic requirements, and familial aggregation were recorded. Results: Sixty-eight Roma/Gypsy patients were identified, 29 of them being women. The mean age at diagnosis of IBD was 24.9 +/- 9.5 years, and the mean time elapsed since diagnosis was 96.6 +/- 72.2 months. Roma/Gypsy IBD patients showed a significantly higher rate of familial aggregation (43%) than their Caucasian controls (9%) (p = 0.00001). CD in Roma/Gypsies had more often a complicated pattern (mainly penetrating) while UC patients showed a marked trend to more often developing extraintestinal manifestations. In addition, Roma/Gypsy IBD patients had a somewhat greater need for immunosuppressants, biological agents or surgery. Conclusions: These are the first data on IBD in Roma/Gypsy patients. Familial aggregation is the most prominent feature in these patients, suggesting a predominant role of genetics in its pathogenesis. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

avoidant/restrictive food intake disorder (ARFID) is a new eating disorder category among eating disorders. Its recent incorporation explains the lack of studies evaluating the optimal treatment and follow-up of patients with this disorder.we present the case of a 20-year-old patient with 3-week dysphagia and 20% weight loss. After ruling out organic disorders, he was diagnosed with ARFID and required parenteral and tube feeding until the improvement of the eating disorder.in this patient, severe caloric malnutrition secondary to the eating disorder made it necessary to turn to the parenteral and enteral approach until the behavioral modification and progressive food exposure were effective. The absence of etiological treatment makes cognitive behavioral intervention, along with the correction of nutritional deficiencies, the preferred approach.Introducción: el trastorno de evitación/restricción de la ingesta alimentaria es una nueva categoría diagnóstica en el espectro de trastornos de la alimentación. Su reciente aparición explica la falta de estudios que evalúen el tratamiento y seguimiento de pacientes con esta patología.Caso clínico: presentamos el caso de un paciente de 20 años con disfagia de tres semanas de evolución y pérdida del 20% de peso, diagnosticado de trastorno de evitación/restricción de la ingesta alimentaria tras descartar organicidad del proceso, con necesidad de nutrición parenteral y enteral como tratamiento nutricional hasta mejoría clínica.Discusión: en este paciente, la desnutrición calórica grave secundaria al trastorno alimentario hizo necesario recurrir al aporte parenteral y enteral hasta la modificación conductual y la reintroducción paulatina de la alimentación por vía oral. La ausencia de tratamiento etiológico hace que la terapia conductual junto con la corrección de los déficits nutricionales sean la base del manejo.

Background The ideal length of treatment with thiopurines in patients with ulcerative colitis (UC) in sustained remission remains unknown. It is widely accepted that the drug withdrawal is associated with a worse outcome. The aim of this study was to analyze the outcome after this withdrawal and to identify predictors of relapse. Methods A multicenter and retrospective study was designed. A total of 102 patients with UC who discontinued thiopurines in a situation of sustained remission were included. All the patients were followed up until last revision or until relapse (understood as the occurrence of signs and symptoms of UC that required a rescue treatment). Results After thiopurines withdrawal, overall relapse was recorded in 32.35% of the patients: 18.88% in the first year, 36.48% in the third, and 43.04% in the fifth year after withdrawal. On multivariate analysis, predictors of relapse were the time from diagnosis of UC until the starting of thiopurines (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.01-1.02; P = 0.039), the number of relapses before the withdrawal (HR, 1.3; 95% CI, 1.01-1.66; P = 0.029), pancolitis (HR, 5.01; 95% CI, 1.95-26.43; P = 0.028), the duration of treatment with thiopurines (HR, 0.15; 95% CI, 0.03-0.66; P = 0.013) and the situation of biological remission at withdrawal (HR, 0.004; 95% CI, 0.0001-0.14; P = 0.002). Conclusions The withdrawal of thiopurines in patients with UC, although in sustained remission, is related to a high relapse rate. Clinical variables such as the extent of the disease, the duration of treatment or time from diagnosis to the start of thiopurines should be considered before stopping these drugs.

This study examines the resources utilization in patients with Crohn's disease (CD) during the year before (Y - 1) and after (Y + 1) starting treatment with adalimumab and the drug's efficiency.Observational, multicenter, prospective cohort study of patients with CD naive to biological drugs. The proportion of patients with CD Activity Index (CDAI)150 was considered as the effectiveness variable. Costs considered were direct costs (DC) related to the use of health care resources, and indirect costs (IC) related to sick leave in Y - 1 and Y + 1. Adalimumab efficiency was estimated as the incremental cost/effectiveness ratio. A deterministic sensitivity analysis was performed building 3 scenarios: base case, the least favorable, and the most favorable case for adalimumab.In the cohort of 126 patients (50.8% men; age 39.1 ± 13.8 yr), the proportion of patients in remission increased from 34.1% by the end of Y - 1 to 83.3% by the end of Y + 1. Although the DC increase by the use of adalimumab, the use of doctor visits, emergency room visits, laboratory tests, diagnostic examinations, and nonbiological drug treatment were lower (P0.05) in Y + 1 than Y - 1. In the base case scenario, considering only DC, the incremental cost/effectiveness ratio was €31,308 and including IC, it was €28,936. In patients with CDAI150 at the onset, incremental cost/effectiveness ratio was €20,119 and €18,223, considering DC alone or included IC, respectively.In patients with CD, adalimumab increases pharmacological costs at the expense of biological therapy but reduces the cost of other drugs, the use of health care resources, and IC. Adalimumab efficiency is 30% greater in patients with CDAI150.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age =50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Iron deficiency without anaemia (IDWA) is commonly found in outpatients with inflammatory bowel disease (IBD) in an even higher proportion than anaemia. However, its true prevalence and possible impact on health-related quality of life (HRQoL) are unknown. The objectives of this study were: to establish the prevalence of IDWA, identify possible associated factors and measure their impact on HRQoL.127 patients with IBD in an outpatient setting were consecutively included in an observational, descriptive, cross-sectional study. IDWA was defined as ferritin levels of100 ng/ml with inflammatory activity or ≤30 ng/ml without it, with transferrin saturation of ≤16%, and with normal haemoglobin levels. HRQoL was assessed using two questionnaires: the IBDQ-9 for symptoms related to IBD and the FACIT-F to measure the presence of fatigue. Fatigue was considered extreme with a score of ≤30 points.The prevalence of IDWA was 37%. Variables associated with its occurrence were female gender (OR=2.9; p=.015) and the presence of inflammatory activity (OR=9.4; p=.001). Patients with IDWA presented HRQoL questionnaires with lower overall scores; decreases of 6.6 (p.001) and 4.3 (p=.037) points in the IBDQ-9 and the FACIT-F were recorded, respectively. In addition, an increase of 29.4% in the presence of extreme fatigue was observed.The prevalence of IDWA is considerable in outpatients with IBD. IDWA is associated with female gender and inflammatory activity. It has a clear negative impact on HRQoL. A more active approach is needed to treat this complication.

Background and aim The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. Material and method Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. Results Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD ± 3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR = 0.54, 95% CI = 0.29–0.98, p = 0.04) and detectable infliximab levels at the time of switching (HR = 0.03, 95% CI = 0.001–0.89, p = 0.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (p = 0.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. Conclusion Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P = 0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P = 0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P < 0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar effi cacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefi t of sequential CyA-IFX for CyA non-responders is acceptable.

Resumen El objetivo clasico del tratamiento de los pacientes con colitis ulcerosa (CU) ha sido inducir y mantener la remision. Sin embargo, este objetivo no ha demostrado su utilidad para evitar la aparicion de complicaciones a largo plazo. Los objetivos actuales del tratamiento intentan cambiar la tendencia a la complicacion de la enfermedad. La cicatrizacion de la mucosa intestinal ha supuesto una estrategia terapeutica que, ya en algunos estudios, ha mostrado mejorar el pronostico del paciente a largo plazo. En el caso de la CU, ha mostrado disminuir la recidiva, el riesgo de cancer colorrectal (CCR), la necesidad de cirugia y mejorar la calidad de vida del paciente. Los farmacos que han conseguido una mayor evidencia para no solo inducir, sino tambien mantener la cicatrizacion de las lesiones, han sido los salicilatos y las terapias biologicas. Es posible que en un futuro proximo tengamos que emplear la monitorizacion endoscopica en la practica clinica para evaluar la respuesta al tratamiento y actuar en funcion de la persistencia o no de lesiones.

Introducción: el trastorno de evitación/restricción de la ingesta alimentaria es una nueva categoría diagnóstica en el espectro de trastornos de la alimentación. Su reciente aparición explica la falta de estudios que evalúen el tratamiento y seguimiento de pacientes con esta patología.Caso clínico: presentamos el caso de un paciente de 20 años con disfagia de tres semanas de evolución y pérdida del 20% de peso, diagnosticado de trastorno de evitación/restricción de la ingesta alimentaria tras descartar organicidad del proceso, con necesidad de nutrición parenteral y enteral como tratamiento nutricional hasta mejoría clínica.Discusión: en este paciente, la desnutrición calórica grave secundaria al trastorno alimentario hizo necesario recurrir al aporte parenteral y enteral hasta la modificación conductual y la reintroducción paulatina de la alimentación por vía oral. La ausencia de tratamiento etiológico hace que la terapia conductual junto con la corrección de los déficits nutricionales sean la base del manejo.

Background and aims: An evaluation is made of the utility of fecal calprotectin in predicting relapse in patients with inflammatory bowel disease (IBD). The possible differences in its predictive capacity in Crohn's disease (CD) versus ulcerative colitis (UC), and the different phenotypes, are also examined. Methods: This is a prospective study with 135 patients diagnosed with IBD in clinical remission for at least 3 months. The patients submitted a stool sample within 24 hours after the baseline visit, for the measurement of fecal calprotectin. All patients were followed-up on for one year. Results: Sixty-six patients had CD and 69 UC. Thirty-nine (30%) suffered from relapse. The fecal calprotectin concentration was higher among the patients with relapse than in those that remained in remission: 444 µg/g (95% CI 34–983) versus 112 µg/g (95% CI 22–996); p 200 µg/g relapsed 4 times more often than those with lower marker concentrations. In UC, calprotectin > 120 µg/g was associated with a 6-fold increase in the probability of disease activity outbreak. The predictive value was similar in UC and CD with colon involvement and inflammatory pattern. In this group, calprotectin > 120 µg/g predicted relapse risk with a sensitivity of 80% and a specificity of 60%. Relapse predictive capacity was lower in patients with ileal disease. Conclusions: Fecal calprotectin may be a useful marker for predicting relapse in patients with IBD. Its predictive value is greater in UC and CD with colon involvement and inflammatory pattern, compared with ileal CD. * Abbreviations : CRP : C-reactive protein CD : Crohn's disease CDAI : Crohn's Disease Activity Index ESR : erythrocyte sedimentation rate IBD : inflammatory bowel disease TW : Truelove Witts UC : ulcerative colitis

Resumen Fundamento y objetivo Aunque parece que no hay un aumento en la prevalencia de infeccion por el virus de la hepatitis B (VHB) en pacientes con enfermedad inflamatoria intestinal (EII), se especula que la necesidad de exploraciones invasivas e intervenciones quirurgicas situa a estos pacientes dentro de un grupo de riesgo para contraer esta infeccion. Ademas, el uso cada vez mas frecuente de inmunomoduladores puede conducir a una reactivacion virica latente. El objetivo de este trabajo fue evaluar la eficacia de la vacuna contra el VHB en pacientes con EII y las circunstancias que pueden influir en su resultado. Pacientes y metodos Desde el ano 2006, se determinaron los marcadores serologicos de los virus B y C de la hepatitis en los pacientes con EII atendidos en esta consulta medica de forma consecutiva. La posterior determinacion de los anticuerpos contra el antigeno de superficie del VHB (anti-HBs) diferencio entre reactivos o no a la vacuna, y se considero como respuesta valores iguales o superiores a⩾10 mUI/ml. Resultados Se incluyo en el estudio a 129 pacientes. Cincuenta y seis pacientes (43,4%) habian recibido algun tratamiento inmunomodulador previo a la vacuna. En 85 pacientes (65,9%) la vacuna no indujo una respuesta adecuada: 36 pacientes no crearon anti-HBs y en 49 pacientes se desarrollaron titulos inferiores a 10 mUI/ml. El unico factor implicado en la respuesta de la vacuna fue la edad, de forma que en los pacientes mas jovenes la eficacia de la vacuna fue mayor (media de 30,91 [14,8] frente a 39,91 [14,2] anos, p Conclusiones En mas de la mitad de los pacientes con EII no se desarrollo una respuesta adecuada a la vacuna del VHB. El unico factor relacionado con una mejor eficacia fue la edad mas joven. Queda por demostrar si una cuarta dosis o si la revacunacion completa aumentarian esta tasa de respuesta.

Fundamento y objetivo El dolor abdominal y la diarrea son sintomas comunes en la poblacion general que no permiten discriminar enfermedad intestinal organica. La colonoscopia es la prueba de referencia, pero es cara, invasiva, no puede repetirse frecuentemente y supone una gran carga asistencial. La calprotectina fecal (CPF) es un marcador facil y rapido de medir, no invasivo y barato, que podria detectar la enfermedad organica en la zona del colon. El objetivo de nuestro estudio es valorar la utilidad de este marcador para predecir una colonoscopia patologica y correlacionar sus valores con el grado de actividad en la enfermedad inflamatoria intestinal (EII). Pacientes y metodo Se determino la calprotectina en muestras fecales (mediante enzimoinmunoanalisis) en 190 personas sometidas a una colonoscopia. Los diagnosticos endoscopicos fueron: 117 normales, 28 polipos colonicos, 20 cancer colorrectal (CCR) y 25 EII. El analisis de los datos se realizo con el programa SPSS 11.0. Resultados La media (DE) de CPF estaba aumentada en CCR (726,6 [533] mg/kg) y EII (2.171,1 [2.133,6] mg/kg). No hubo diferencias en pacientes con polipos (158,3 [15,8] mg/kg). En pacientes con EII, los valores se correlacionaron con el grado de actividad de la enfermedad. El valor de corte fue 217 mg/kg, y se obtuvo una sensibilidad de la CPF del 85% y un valor predictivo negativo del 93%. En el grupo control, la unica variable que se relaciono con un aumento de CPF fue la medicacion previa con acido acetilsalicilico (AAS) y/o antiinflamatorios no esteroideos (AINE). Conclusiones La CPF es una prueba no invasiva, barata y sensible para detectar enfermedad organica en la zona del colon, que puede ser util para seleccionar a pacientes que deben someterse a una colonoscopia. Se correlaciona con el grado de actividad en la EII. La toma de AAS y/o AINE podria aumentar la tasa de falsos positivos.

The classical aim of the treatment of ulcerative colitis is to induce and maintain remission. However, this aim has not been shown to prevent long-term complications. Current treatment goals attempt to prevent complications. In some studies, healing of the intestinal mucosa has been shown to improve long-term outcomes. In ulcerative colitis, mucosal healing reduces recurrence, the risk of colorectal cancer and the need for surgery, and improves patients' quality of life. The drugs for which there is greatest evidence of their efficacy in inducing and maintaining mucosal healing are salicylates and biological agents. In the near future, endoscopic monitoring may be required to evaluate response to the treatment and decisions may have to be taken according to the persistence or disappearance of these lesions.

Spontaneous intramural dissection of the esophagus (SIDE) is an unusual clinical entity. It is a benign disease that, despite its alarming endoscopic appearance, usually responds well to conservative management and has an excellent prognosis. Nevertheless, some situations require emergency surgical treatment. These situations include esophageal perforation with mediastinitis, massive bleeding, and abscess, among others. Upper gastrointestinal endoscopy is a useful diagnostic test when radiological examinations (hydrosoluble contrast esophagogram, computed tomography, or magnetic resonance imaging) have excluded perforation. We present the case of a 42-year-old woman who was admitted to our hospital complaining of acute chest pain, dysphagia, and odynophagia. Because of the persistence of symptoms and diagnostic uncertainty (SIDE versus complicated esophageal duplication cyst) surgery was performed. The definitive diagnosis was SIDE.

To determine the value of systemic cytokines as predictors of relapse in inflammatory bowel disease (IBD).A prospective study with 135 patients in clinical remission for at least 3 months. At enrollment, a venous blood was drawn in order to measure, by an ELISA test, the following cytokines: TNFalpha, TNFalpha-R1 and R2, IL-16, IL-1beta, IL 2, IL-R2, IL-6, IL-10, and IFNgamma. All patients were followed-up for one year.Sixty-six patients had Crohn's disease (CD) and 69 had ulcerative colitis (UC). Thirty-nine (30%) had a relapse. Forty-four percent were receiving immunomodulatory therapy. No differences were found regarding detection and baseline concentration of the various cytokines between patients with CD and UC, or between patients with or without ongoing use of immunomodulators. The detection and concentration levels of cytokines were not associated with the risk of relapse of IBD.Systemic cytokines are of little value to predict IBD relapse.

Adalimumab Dose Escalation Is Effective for Managing Loss of Response in Ulcerative Colitis Carlos Taxonera, Eva Iglesias Flores, Fernando Munoz, Marta Calvo, Manuel Barreiro-de Acosta, David Busquets, Xavier Calvet, Antonio Rodriguez, R. Pajares, Javier P. Gisbert, Pilar Lopez-Serrano, Jose Lazaro Perez-Calle, Angel Ponferrada Diaz, Cristobal De la Coba, Fernando Bermejo, Maria Chaparro, Cristina Alba, David Olivares, Ignacio Fernandez-Blanco

Abdominal pain and diarrhoea are common symptoms in the general population. The colonoscopy is the gold standard method of detecting an organic pathology in the colon. However, it is invasive; it can not be repeated frecuently; it is expensive; and the system is overloaded. Fecal calprotectin (FCP) is a marker that may detect organic pathologies of the colon. The aims of this study were to analyze the usefulness of FCP to predict an abnormal colonoscopy and to correlate the levels of FCP with the degree of activity in inflammatory bowel disease (IBD).190 people were included in the study. All of them underwent a colonoscopy and a stool sample. People were divided in: normal colonoscopy: 117 people, and 28 colon adenomas, 20 colorectal cancer (CRC) and 25 IBD.The mean (SD) FCP concentration was 2,171.1 (2,133.6) mg/kgin patients with IBD and 726.6 mg/kg (533) in CRC. Both results were significantly elevated compared with those of healthy controls [114 (113)] mg/kg In patients with IBD, their levels correlated directly with the activity of the inflammation. 217 mg/kg was the best cut-off for discriminating patients with organic colon disorders. The sensibility was 85% and NPV was 93%. NSAIDs use was a clinical variable which was connected with a high FCP concentration in patients with normal colonoscopy.The higher levels of FCP were found in people with IBD and CRC. The measurement of FCP is a non-invasive, inexpensive, reliable and easily measured test. Among people with abdominal pain and diarrhoea, testing for FCP allows us to select those who must undergo a colonoscopy. NSAIDs can raise the levels of FCP in people with normal colonoscopies.

One UC patient (9.1%) had synchronous adenocarcinomas at rectum and descending colon. The histologies of CRCs were as follows; moderately differentiated adenocarcinoma in seven (36.8%), mucinous adenocarcinoma in five (26.3%), poorly differentiated adenocarcinoma in three (15.8%), well differentiated adenocarcinoma in three (15.8%), and signet ring cell carcinoma in one (5.3%). The stage distribution of cancer was as follows; I in one (5.3%), II in seven (36.8%), III in three (15.8%) and IV in eight (42.1%). The cumulative risks of CRC at 10 years after UC, CD, and IBD diagnosis were 0.4%, 0.4%, and 0.4%, respectively. They were 4.9%, 6.6% and 5.5%, respectively after 20 years (Figure 1).