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Background The risk of splanic vein thrombosis (SVT) -as defined as that involving the portal vein and/or its intrahepatic branches, mesenteric, splenic and/or suprahepatic veïns is mainly observed, among others, in inflammatory abdominal conditions. Thromboembolic complications are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, characteristics, risk factors and evolution of SVT in patients with IBD. Our aims were to describe the characteristics of SVT in patients with IBD, diagnostic explorations, treatment and evolution. Methods Retrospective, multicentre, descriptive study of the ENEIDA registry with a diagnosis of SVT. In addition to epidemiological and clinical features of IBD, we recorded specifically diagnosis, treatment, disease activity at the time of SVT and outcome of SVT. Results Over 59,000 IBD patients in the ENEIDA registry, only 49 episodes of SVT were identified (35 Crohn’s / 14 Ulcerative Colitis); 69% men, median age 42 years old, 35% smokers. 37% had a past history of surgery and/or abdominal inflammatory conditions, 16% extra-intestinal neoplasia, 23% baseline immune or hematologic conditions and 14% liver disease. Finally, 16% had a previous episode of venous thrombosis. The most frequent forms of clinical presentation were abdominal pain with/without fever (59%), and radiological findings in the setting of active IBD (25%). ST coincided with IBD activity in 76% of cases. The diagnosis of SVT was based in the findings of an abdominal CT in 82%. The most frequent localition of SVT were intrahepatic portal branches (51%) and superior mesenteric vein (47%). Only 47% had a basic aetiological study, and 37% underwent gastroscopy (median 7 months from the diagnosis of SVT) showing oesophageal varices in 67%. Anticoagulation therapy was prescribed in 94% of the episodes (74% within the first month since diagnosis), for a median of 7 months. In 90% of the cases, there was a further radiological assessment, 61% of which showing the resolution of the SVT (median of 5 months from the beginning anticoagulation treatment). Conclusion SVT seems to be a rare (or underdiagnosed) complication in IBD patients, it is mostly associated with disease activity and evolves suitably when anticoagulation therapy is suitably started.

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.

Resumen El uso de anticuerpos contra el factor de necrosis tumoral alfa (anti-TNF) aumenta el riesgo de tuberculosis (TB) en pacientes con enfermedad inflamatoria intestinal (EII). GETECCU publico las primeras guias de cribado de TB para pacientes con EII en 2003 y las reviso en 2006. Sin embargo, la implementacion en la practica clinica de nuevas pruebas diagnosticas como los test de liberacion de interferon gamma, el mayor conocimiento epidemiologico y clinico de la TB en el contexto de tratamiento anti-TNF y la evidencia de que las recomendaciones de cribado de infeccion tuberculosa latente en pacientes candidatos a terapia anti-TNF disminuye pero no erradica los casos de TB han motivado la revision de las recomendaciones de GETECCU al respecto.

Resumen La mesalazina es el farmaco de eleccion en pacientes con formas leves-moderadas de colitis ulcerosa, tanto para inducir la remision clinica como para su mantenimiento. De hecho, la mitad de los pacientes se controlaran unicamente con mesalazina a lo largo de su evolucion. Globalmente, se considera un farmaco seguro, con pocos efectos adversos. Aun asi, se han descrito algunos casos de hipersensibilidad a aminosalicilatos de caracter idiosincratico que suelen conllevar la retirada del farmaco y, por tanto, limitar de forma notable las posibilidades de manejo terapeutico, especialmente en pacientes con actividad leve o moderada o en pacientes con afectacion exclusiva rectal. Presentamos 2 casos de proctitis ulcerosa, en los que se sospecho alergia a la mesalazina, lo que conllevo un control inadecuado de la enfermedad. Tras la realizacion del estudio inmunoalergico, se descarto reaccion de hipersensibilidad, se reintrodujo el farmaco y se logro la remision clinica de forma rapida y prolongada.

Resumen Aunque la mayoria de pacientes con colitis ulcerosa deberian recibir tratamiento topico por via rectal, los estudios de practica clinica han demostrado que este esta infrautilizado. El proposito de este articulo es el de responder a 10 preguntas concretas sobre que farmacos estan disponibles para uso topico, su forma de presentacion, formulacion, y metodos de aplicacion, asi como cual de ellos es mas eficaz y en que forma de presentacion de la colitis ulcerosa. Asi mismo, se evalua la posibilidad de combinar diferentes formulaciones y vias de administracion, y la utilidad en la fase de remision de la enfermedad. Por ultimo, se hacen una serie de recomendaciones para una mejor informacion de los pacientes acerca de una correcta aplicacion y administracion.

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.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. Inclusion criteria: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. Exclusion criteria: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Idiopathic myointimal hyperplasia of mesenteric veins is a very rare disease occurring in young male patients, with no more than eight cases reported in the world literature. It causes venous ischemia in the sigmoid colon and rectum that clinically resembles inflammatory bowel disease. Pneumatosis intestinalis is also a rare condition usually associated to a wide range of diseases including bowel ischemia. We herein report on a case of pneumatosis intestinalis associated to idiopathic myointimal hyperplasia of mesenteric veins. To our knowledge, this is the first report of such an association, and the first one of idiopathic myointimal hyperplasia of mesenteric veins occurring in a female patient as well.

Eur J Clin Invest 2011; 41 (10): 1047–1053 Abstract Background Intestinal commensal flora seems to be a requisite for both human and experimental intestinal inflammation. Our aim was to assess the immunological changes in the colon of IL-10(−/−) mice depending on the environmental conditions. Materials and methods Twelve wild-type (WT) and 24 IL-10(−/−) 4-week-old mice were kept under specific pathogen-free (SPF) conditions for 4 weeks. Half of them were transferred to a conventional environment. Mice were sacrificed at 12 weeks of age, and the incidence and severity of colitis was assessed. Intraepithelial (IEL) and lamina propria (LPL) lymphocytes were assessed for phenotype and apoptosis by flow cytometry. Toll-like receptors 2 (TLR2) and TLR9 expression was assessed by real-time PCR. Immunohistochemical analyses for cell apoptosis, TLR2 and MyD88 were also performed. Results IL-10(−/−) mice shifted to conventional conditions showed a greater incidence (66% vs. 50%) and severity of colitis than animals kept under SPF conditions (P = 0·009). The number of CD3+ IEL was higher and their apoptosis rate lower in IL-10(−/−) than in their WT counterparts, regardless of the environment. In LPL, however, these differences were only observed in mice shifted to conventional conditions. TLR2 expression was significantly increased in SPF-housed IL-10(−/−) mice when compared to WT controls. Immunohistochemistry demonstrated the loss of TLR2 and MyD88 in damaged areas. Conclusions In SPF conditions, IL-10 deficiency appears to be compensated by an increased epithelial TLR2 expression, thus resulting in a milder colonic damage. However, in conventional conditions, this compensatory mechanism would be exceeded inducing a more severe colonic damage with activation of LPL immune cells.

Portal hypertension (PH) is a complication that may occur in patients with inflammatory bowel disease (IBD). In these patients, the etiology of PH may not be alcoholic or viral cirrhosis (which cause 90% of cases in the general population). Consequently, etiologic study of PH in patients with IBD should always include a wide spectrum of possibilities. Moreover, the development of PH in IBD patients often requires a distinct therapeutic approach to IBD (both medical and surgical) as PH may be a contraindication for some drugs and is a risk factor for surgical morbidity and mortality. We present the cases of two patients with IBD who developed PH and review the most likely causes of PH in IBD, as well as preventive and therapeutic strategies.

Background Scarce data are available in Europe on the cost of treatment for ulcerative colitis (UC). Aim To assess the cost of illness of moderate-to-severe UC in two scenarios: traditional treatment versus alternative treatment incorporating granulocyte, monocyte adsorption – apheresis (GMA-Apheresis; Adacolumn ® ). To determine the relative cost-effectiveness of both options in steroid-dependent patients. Methods One-year cost-of-illness and cost-effectiveness analysis from the third-payer perspective using a decision tree model was carried out. Probabilities of each event were derived from the literature and an expert panel. Direct medical costs were obtained from official sources (€2004). Effectiveness was measured by the proportion of patients achieving clinical remission. Results The average annual cost per patient treated with traditional treatment was estimated to be €6740; with GMA-Apheresis, the cost was estimated to be €6959. In steroid-dependent patients, the average annual cost was €6059 and €11,436, respectively. The proportion of patients achieving clinical remission with GMA-Apheresis was 22.5% higher. As second- and third-line therapy, a new course of corticosteroids and surgery was avoided in 18.5 and 4% of patients, respectively. Conclusions Incorporating GMA-Apheresis (Adacolumn ® ) in the therapeutic management of moderate-to-severe UC patients is cost-effective and implies savings related to the reduction of adverse effects derived from corticosteroid use and to the decreased number of surgical interventions.

Objetivos La reseccion quirurgica todavia es un pilar fundamental en el tratamiento de la enfermedad de Crohn (EC); sin embargo, la recurrencia es la norma. El objetivo del presente estudio es evaluar la aparicion de recurrencia de EC en una serie de pacientes a quienes se practico una reseccion quirurgica, tratados posteriormente con azatioprina (AZA) o mesalazina (5-ASA), e identificar los factores asociados a la recurrencia. Metodos Se revisaron las historias clinicas de los pacientes con EC, a quienes se practico una reseccion intestinal, durante un periodo de 4 anos. Solo fueron incluidos en el estudio los que recibieron AZA o 5-ASA como profilaxis de la recurrencia. Resultados Se incluyeron 33 pacientes tratados con AZA y 16 con 5-ASA. Se constato una recurrencia endoscopica en el 8,6 y el 87,5% de los pacientes del grupo AZA y 5-ASA, respectivamente (p Conclusion AZA parece ser mas eficaz que 5-ASA en la prevencion de la recurrencia endoscopica posquirurgica en la EC. Son necesarios estudios prospectivos con seguimiento a largo plazo para establecer la verdadera utilidad de AZA en esta situacion clinica.

Immunosuppressive agents (azathioprine, methotrexate) are increasingly being used in the treatment of inflammatory bowel disease. The use of immunosuppressive agents is associated with a greater risk of opportunistic infections, the most frequent of which are those caused by cytomegalovirus and varicella zoster virus. We present four cases of opportunistic infections due to Herpesviruses in patients undergoing immunosuppressive treatment with azathioprine for Crohn's disease. We also review the literature published on this topic. Two patients presented cutaneous varicella complicated by pneumonia and esophagitis respectively, one patient had cutaneous herpes zoster and the other had fatal pneumonia possibly caused by the Herpesvirus. In the first three the clinical course of the infection was favorable after withdrawing immunosuppressant treatment and initiating treatment with aziclovir. In patients Crohn's disease azathioprine treatment increases the risk of opportunistic infection by Herpesvirus. However, in the absence of other factors that increase immunosuppression, these infections usually have a benign course with specific antiviral therapy.

Este documento ha sido elaborado por un grupo de miembros del Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) en varias fases, que han incluido su discusion libre durante varios meses, tanto por las personas encargadas de redactarlo como por cualquier otro miembro del grupo que ha querido colaborar. Asimismo, el documento se discutio abiertamente en la ultima reunion cientifica de GETECCU en octubre de 2001, y se han reflejado en el mismo aquellas sugerencias que fueron aceptadas por consenso. El objetivo fundamental de este documento es proporcionar a los miembros de GETECCU, y en general a los gastroenterologos y medicos interesados en el uso de infliximab en la enfermedad de Crohn, una herramienta util para su trabajo diario, que sintetiza los conocimientos actuales sobre el farmaco, desde una perspectiva independiente y cientifica. Al tratarse de un campo en continuo cambio, el documento sera actualizado permanentemente. Estas actualizaciones se encuentran disponibles en www.aegastro.es y en www.prous.es/ geteccu. A esas direcciones pueden remitir los lectores aquellas sugerencias que crean necesarias.

Summary: Epidemiological utility and characteristics of the Beck Depression Inventory (BDI) were examined in a sample of 304 nonclinical adolescents. Psychopathological diagnoses according ICD-10 criteria were assessed by the Schedules for Clinical Assessment in Neuropsychiatry. The female BDI scores were significantly higher than the male scores. The depressed adolescent scores were significantly higher than for nondepressed adolescents. Different scores as discriminators of depression subtypes were reported. The BDI pessimism item was the most important predictor of the total BDI score. Gender differences were found in depressive symptomatology. According to the rates of sensitivity and specificity, the best cutoff scores found were 16 and 10 for major depression and dysthymia, respectively. In conclusion, the BDI proved to be a reliable and valid instrument that could be used as a depression screening in nonclinical adolescents.

Hepatocarcinoma (HCC) is the most frequent primary malignant hepatic tumour. These tumours usually develop in cirrhotic liver; for this reason, periodic screening using alphafetoprotein determination and abdominal ultrasonography is considered in cirrhotic patients with preserved hepatocellular function. This strategy allows early detection of HCC, increasing the proportion of curable tumours. The most frequent metastasic dissemination is portal vein neoplasic thrombosis, being unusual the occurrence of spread metastases in other organs. We present 3 cases of atypical HCC metastasis with non specific clinical manifestations which initial diagnosis was wrong. Because of a longer survival of these patients in recent years, spread metastasis might be considered in patients with known HCC and non specific symptoms.

The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy.Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn.A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio = 0.6; 95% confidence interval = 0.4-0.9, P = 0.02) was the only predictor of favorable GPO, whereas maternal age35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO.The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

Background Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. Aim To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. Methods We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. Results In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). Conclusion These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers.

Background The first infliximab biosimilar was approved in Europe in Sept. 2013 for all indications authorised for originator infliximab, including those in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Confusion exists around differences between biologics and biosimilars, the definition of a biosimilar and the process by which they are manufactured. In addition, there are varying levels of comfort in the types of patients to whom biosimilars could be prescribed. Objectives We aimed to understand rheumatologists9 current perspectives and knowledge on biosimilars, including regulatory aspects and manufacturing principles, as well as comfort with prescribing. Methods 222 rheumatologists chosen randomly across 11 countries (Finland, France, Germany, Hungary, Ireland, Italy, Norway, Portugal, Spain, Sweden, and UK) participated in a web-based survey from Jun. to Aug. 2015. Key eligibility criteria: being in a practice with at least 30% of patients with Rheumatoid Arthritis or 5% with Ankylosing Spondylitis; at least 15% of these treated with a biologic; physicians in the survey prescribed infliximab (originator or biosimilar) to at least one patient and have access to biosimilar infliximab (able to prescribe biosimilar infliximab). Most (72%) had prescribed biosimilar infliximab to at least one patient. Results 97% of rheumatologists indicated being familiar or very familiar with biosimilars. Despite a high level of familiarity, only 48% correctly identified the EMA definition of a biosimilar; the remainder incorrectly defined biosimilars as the equivalent of generics for biologics (16%) or as similar biologics having the same mechanism of action as the originator (36%). 65% of rheumatologists cited either limited or no knowledge of biologic manufacturing processes. Most rheumatologists preferred to prescribe biosimilars to naive patients or those who stopped responding to their current biologic. On a scale of 1 to 10 (10 = extremely comfortable), rheumatologists rated their level of comfort in prescribing biosimilars as 6.5 (significantly lower than gastroenterologists answering an identical question in a parallel survey; mean = 6.9, p=0.002 ). There was a general correlation between the length of exposure to biosimilars and willingness to prescribe, although exceptions were noted (e.g., Portugal, Spain). Knowledge regarding biosimilar manufacturing standards and comfort in prescribing were not correlated. Conclusions Knowledge and awareness of biosimilars is growing among EU rheumatologists and there are high levels of comfort in prescribing biosimilars; however, confusion still exists with regard to definitions, regulations and manufacturing standards. Disclosure of Interest H. Kellner: None declared, E. Domenech Grant/research support from: MSD, AbbVie, Hospira, Kern Pharma, Celgene, and Jansenn, Speakers bureau: MSD, AbbVie, Hospira, Kern Pharma, Celgene, and Jansenn, P. Lakatos Grant/research support from: AbbVie, MSD and Hospira, Speakers bureau: AbbVie, Celltrion, EGIS, Falk Pharma GmbH, Ferring, Hospira, Kyowa Hakko Kirin Pharma, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, Pharmacosmos, Roche and Takeda, J. Marsal: None declared, C. Agboton: None declared, M. Cassese: None declared, N. Georgitseas: None declared, S. Anwar: None declared, A. Venugopal: None declared, P. Audhya: None declared

SIRS, We read with interest the study of Saito et al. in which predictors of response to i.v. ciclosporin in steroid-refractory, severe, ulcerative colitis (UC) were evaluated. The study provides additional data strengthening the idea that the more severe is disease activity at baseline or soon after starting ciclosporin therapy (as reflected by a persistently high Lichtiger score or a decrease in total serum protein concentration) the poorer is the outcome. 3 However, some methodological issues might limit the application of their proposed score and decision tree. First, the study deals with a highly selected population with severe disease activity, despite i.v. corticosteroids (Lichtiger score >9), which is not the usual clinical scenario when rescue therapies, such as ciclosporin or infliximab, are used in UC patients. In addition, an outstanding proportion of patients in the study presented additional factors for unresponsive disease, such as cytomegalovirus reactivation, Clostridium difficile disease or unsuccessful attempts with other rescue therapies (infliximab or leukocytoapheresis) prior to ciclosporin therapy. Second, all patients were treated with i.v corticosteroids for at least 5 days; despite they all had persistent severe activity. Finally, the authors chose to define response to ciclosporin as the avoidance of colectomy within the following 3 months. Nowadays, when clinical experience with calcineurinic antagonists and anti-TNF agents in UC is wide, 5 therapeutic decisions should be taken in a timely manner to improve drug efficacy and clinical outcomes. Two prospective studies showed that response to corticosteroid therapy in UC is accurately predicted after third day 8 and, therefore, corticosteroid therapy should not be further prolonged, particularly, in severely ill patients. Early introduction of rescue therapies not only may improve their efficacy, but also could allow administering sequential therapies in safer conditions. In this sense, not the need of colectomy, but rather the need for rescue therapies should be the end-point for predictive studies in steroid-refractory UC. In fact, 35% of the patients in the study by Saito et al. achieved a partial response after 14 days of ciclosporin therapy, and some of them were not colectomised, but had to prolong ciclosporin treatment or were switched to leukocytoapheresis, meaning that ciclosporin failed, although colectomy was not performed.