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No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD.RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation.Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p0.0001).Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

Background: To evaluate the cost-effectiveness of tofacitinib in comparison to vedolizumab for the treatment of moderate-to-severe ulcerative colitis (UC) after failure or intolerance to conventional therapy (bio-naive) or first-line biologic treatment (bio-experienced), from the Spanish National Health System (NHS) perspective. Methods: A lifetime Markov model with eight-week cycles was developed including five health states: remission, response, active UC, remission after surgery, and death. Response and remission probabilities (for induction and maintenance periods) were obtained from a multinomial network meta-analysis. Drug acquisition – biosimilar prices included – (ex-factory price with mandatory deductions), adminis- tration, surgery, patient management, and adverse event management costs (€, year 2019) were considered. A 3% discount rate (cost/outcomes) was applied. Probabilistic and deterministic sensitivity analyses (PSA) were conducted. Results: Tofacitinib was dominant versus vedolizumab (both in bio-naive and bio-experienced patients) entailing total cost savings of €23,816 (bio-naïve) and €11,438 (bio-experienced). Differences in quality- adjusted life-year (QALY) were smaller than 0.1 for both populations. PSA results showed that tofacitinib has a high probability of being cost-effective (bio-naïve: 82.5%; bio-experienced: 90.6%) versus vedolizumab. Conclusions: From the Spanish NHS perspective, tofacitinib could be a dominant treatment (less costly and more effective) in comparison to vedolizumab, with relevant cost savings and similar QALY gains.

Resumen Introduccion Desde la publicacion de la primera edicion de la Guia en 2013, se ha generado mucha informacion en torno al tratamiento de la colitis ulcerosa, y se han introducido nuevos farmacos y protocolos de actuacion. La practica clinica ha variado substancialmente, lo que justifica nuevas aproximaciones y una revision exhaustiva, asi como la actualizacion de la evidencia. Material y metodos Se utiliza nuevamente metodologia GRADE, apoyados en una herramienta electronica ( https://gradepro.org ). Los escenarios clinicos son los mismos que en la version previa (induccion y mantenimiento en brote grave y en brote leve-moderado), asi como las variables y su evaluacion. En la guia actualizada, en relacion a la version previa, se eliminan tres preguntas, se anaden 14 y se mantienen 30, con un total de 44 preguntas clinicas. Tras una exhaustiva revision de la evidencia, se actualizan las recomendaciones. Resultados De las 44 preguntas analizadas, en dos de ellas no se ha podido establecer ninguna recomendacion por muy baja calidad de la evidencia, mientras que en las 42 restantes, basados en diferentes grados de calidad de evidencia, se ha formulado una recomendacion de acuerdo con el sistema GRADE. En 25 de estas preguntas la recomendacion final es fuerte a favor; en seis, fuerte en contra; mientras que en siete es debil a favor, y en cuatro debil en contra. Siguiendo los escenarios y las recomendaciones, se proponen seis algoritmos como guia sencilla en la toma de decisiones practicas. Conclusiones Esta actualizacion de la guia previa publicada en 2013 intenta dar respuesta basada en la metodologia GRADE a las diferentes preguntas que nos hacemos diariamente a la hora de decidir el tratamiento mas adecuado de nuestros pacientes con colitis ulcerosa en los diferentes escenarios clinicos.

Resumen Introduccion Ustekinumab, anticuerpo monoclonal que bloquea las interleucinas 12/23, ha demostrado en ensayos clinicos su eficacia para inducir y mantener la remision clinica en la enfermedad de Crohn (EC). Su efectividad y su seguridad en la practica clinica real es menos conocida y podria diferir respecto a los ensayos. Objetivo Evaluar en la practica clinica su efectividad y seguridad (pauta de induccion intravenosa esencialmente), como induccion y a largo plazo, en pacientes con EC refractarios a tratamiento biologico. Material y metodos Analisis retrospectivo multicentrico (6 hospitales aragoneses), que incluye a todos los pacientes (N = 69) con EC en tratamiento con ustekinumab (fuese con induccion intravenosa o subcutanea) que hubiesen alcanzado al menos 16 semanas de seguimiento. La respuesta o remision clinica se ha evaluado en las semanas 16, 24, 32 y 48 mediante el indice de Harvey-Bradshaw. Resultados Se han incluido un total de 69 pacientes, edad media 42 anos, 54% hombres. Un 89,86% (IC 95% [0,805, 0,949]) de los pacientes ha presentado mejoria clinica en la semana 16 (15,95% remision, 73,92% respuesta). En el seguimiento posterior dicha respuesta se ha mantenido. Se han identificado mediante un modelo de regresion ordinal la edad (OR 0,95, p = 0.028) y el habito tabaquico (OR 0,19, p = 0,027) como predictores de mala respuesta al tratamiento, mientras que la necesidad de cambio de biologico por efecto adverso (OR 96, p = 0,00017) y por perdida de respuesta secundaria (OR 7,07, p = 0,034) han sido factores predictores de buena respuesta. No se han reportado efectos adversos graves que obligasen a interrumpir el tratamiento con ustekinumab. Conclusion Ustekinumab es efectivo y seguro en la practica clinica real para lograr la induccion y el mantenimiento de la respuesta en pacientes con EC refractaria. El tabaco y la edad han mostrado ser predictores de mala respuesta, mientras que la indicacion por efecto adverso a biologico previo y por perdida de respuesta secundaria han mostrado ser predictores de buena respuesta.

Objetivo La medida de los resultados percibidos por el paciente en la asistencia de la enfermedad inflamatoria intestinal (EII) adquiere cada vez más importancia. Existe una herramienta sencilla y validada en inglés para este fin: el «IBD-Control». Nuestro objetivo es traducirlo al español, adaptarlo y validarlo. Pacientes y métodos Se tradujo el IBD-Control, generando el instrumento en español «EII-Control», y se validó prospectivamente. Los pacientes cumplimentaban el EII-Control y otros cuestionarios que servían de comparadores de referencia. El gastroenterólogo realizaba una valoración global de la enfermedad, calculaba índices de actividad y registraba el tratamiento. Un subgrupo de pacientes repitió toda la valoración en una segunda visita. Se analizó también la utilidad de escalas resumidas del EII-Control (el EII-Control-8 y el EII-Control-EVA). Resultados Se incluyeron 249 pacientes con EII (101 repitieron la segunda visita). Estándares psicométricos del test: consistencia interna: α de Cronbach para EII-Control 0,83 con fuerte correlación entre EII-Control-8 y EII-Control-EVA (r = 0,5); reproducibilidad: correlación intraclase 0,70 para EII-Control; validez de constructo: correlaciones de moderadas a fuertes entre EII-Control, EII-Control-8 y EII-Control-EVA frente a comparadores; validez discriminante: p

OBJECTIVES 1)To analyze evidence about poor adherence / non-adherence including their prevalences, associated factors, and interventions in ulcerative colitis (UC) patients; 2)To provide a framework to improve poor adherence / non-adherence. METHODS A qualitative approach was applied. A literature review was performed using Medline. Primary searches were performed with Mesh and free texts to identify articles that analyzed prevalence, causes, associated factors, and interventions designed to improve poor adherence/ non-adherence in UC patients. The studies' quality was evaluated using the Oxford scale. The results were presented and discussed in a nominal group meeting, comprising a multidisciplinary committee of six gastroenterologists, one psychologist, one nurse, and one patient. Several overarching principles and recommendations were generated. A consensus procedure was implemented via a Delphi process during which each committee member produced a score ranging from 0 = totally disagree to 10 = totally agree. Agreement was considered if at least 70% of the participants voted ≥7. RESULTS The literature review included 75 articles. Non-adherence rates ranged from 7%-72%. We found a great variability in the methods employed to assess adherence, associated factors, and interventions designed to improve adherence. Overall, eight overarching principles and six recommendations were generated, all of them achieving the pre-established agreement level, including, among others, the identification, classification, and management of non-adherence. CONCLUSIONS Poor adherence / non-adherence are common in UC patients, being a relevant clinical concern. Health professionals should address this issue and actively involve the patients in implementing effective and individualized interventions to improve adherence.

BACKGROUND There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (

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

Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (>60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) >4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

Background Biological drugs for moderate-to-severe ulcerative colitis have changed the therapeutic perspective, while small-molecule inhibitors and new promising drugs suggest new options. Aim Assess comparative efficacy and safety of biological and new small oral drugs: commercialized and under-investigation ones for patients naïve to biological drugs. Methods A systematic review was conducted to identify the randomized clinical trials phase 2 or 3, in adults with moderate-to-severe ulcerative colitis treated with biological drugs (infliximab, adalimumab, golimumab, vedolizumab and etrolizumab) or new oral small molecules (tofacitinib and ozanimod) as first line. A Bayesian network metaanalysis was performed to inform comparative efficacy and safety of different treatments. Efficacy outcomes were clinical remission, clinical response and mucosal healing for induction therapy and clinical remission, mucosal healing and sustained clinical remission for maintenance therapy. Safety was assessed with serious adverse events and rates of infections. Results 14 references were included for network meta-analysis. For induction therapy, infliximab was the best drug for induction of clinical response and remission, while ozanimod showed to be the best for induction of mucosal healing. Tofacitinib had the highest rate of maintaining clinical remission. All treatments were similar for serious adverse events, and vedolizumab and tofacitinib had the highest rates of infections. Conclusion This network meta-analysis suggests infliximab may be the best therapeutic option for moderate-to-severe ulcerative colitis. Vedolizumab seems to have better outcomes in maintenance than in induction therapy and it appears superior to golimumab and adalimumab. Tofacitinib, ozanimod and etrolizumab show encouraging results.

Background A less aggressive phenotype of Crohn’s disease (CD) has been reported in patients with elderly onset CD. Despite this, similar surgical rates among younger and older CD patients have been reported. However, scarce data are available about the risk of postoperative recurrence (POR) regarding the age, and no data are available about the use of immunosuppressants and biological agents for prevention of POR in elderly patients. Our aim was to evaluate the management of CD in the postoperative setting and the rate of surgical POR in CD patients according to the age at surgery. Methods Cohort study including all adult CD patients in the ENEIDA registry (a prospectively-maintained database of the Spanish Working Group in IBD –GETECCU-) who underwent a first intestinal resection with ileo-colonic anastomosis. Patients were grouped regarding their age at the moment of the first surgery: over 60 years (elderly) and between 18 and 60 years of age (controls). Preventive treatment for POR, surgical POR (need for a further intestinal resection) and postoperative morbidity were compared between both groups. Results Out of the 69,740 IBD patients included in the ENEIDA database, 3,982 had a first intestinal resection for Crohn’s disease with an ileo-colonic anastomosis between 2005 and 2020. Of them, 535 were elderly and 3,454 controls. Time from IBD diagnosis to surgery was significantly longer in the elderly (114±128 vs. 93±97 months; p Conclusion The elderly patients show similar rates of surgical POR as compared to younger patients. Given the high risk of thiopurine and anti-TNF-related adverse events, elderly patients with inflammatory pattern would benefit from preventive therapy with safer biologicals.

Background The information regarding IBD patients with COVID-19 suggests that the factors related to bad outcome are older age and comorbidity whereas immunosuppressants do not have a significant impact worsening the disease evolution. To date, there is no information to assess if there are differences in epidemiological, demographical, and clinical characteristics between infected and non-infected IBD patients. Methods Case-control study in IBD patients with COVID-19 (cases) compared to IBD without COVID-19 (controls) in the period March-July/2020 within the ENEIDA registry (promoted by GETECCU and with more than 60.000 IBD patients included). Cases were matched 1:2 by age (±5y), type of disease (CD/UC), gender, and centre. All controls were selected from only one investigator blind to other clinical characteristics of the patients to avoid selection bias. Results 496 cases and 964 controls from 63 Spanish centres were included. No differences were found within the basal characteristics including CD location, CD behaviour, extraintestinal manifestations, family history of IBD or smoking habits. Cases had ≥ 1 comorbidities (cases:43%vs. controls:36%, p=0.01) and occupational risk (cases:27% vs. controls:10.6%, p Conclusion Comorbidities and epidemiological risk factors are the most relevant aspects for the risk of COVID-19 in IBD patients. This risk of COVID-19 seems to be increased by aminosalicylates but not by immunosuppressants or biologics. The attitude regarding treating IBD patients with aminosalicylates during the COVID-19 pandemic deserves a deeper analysis. Funded by the Carlos III Health Institute COV20/00227.

Background and Aims Although commonly used in inflammatory bowel disease [IBD], thiopurines frequently cause intolerance, and switching to a second thiopurine has only been reported in some small series. Ours aims in this study were to evaluate the safety of switching to a second thiopurine in a large cohort, and to assess the impact of age on tolerance. Methods Adult IBD patients from the ENEIDA registry, who were switched to a second thiopurine due to adverse events [excluding malignancies and infections], were identified. At the beginning of thiopurine treatment, patients were divided by age into two groups: 18–50 and over 60 years of age. The rate and concordance of adverse events between the first and second thiopurines, treatment intolerance, and persistence with the second thiopurine were evaluated. Results A total of 1278 patients [13% over 60 years of age] were switched to a second thiopurine. At 12 months, the cumulative probability of switch intolerance was 43%, and persistence with treatment was 49%. Independent risk factors of switch intolerance were age over 60 years (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.07–2.07; p = 0.017) , previous gastrointestinal toxicity [OR 1.4; 95% CI 1.11–1.78; p = 0.005], previous acute pancreatitis [OR 6.78; 95% CI 2.55–18.05; p Conclusions In a large series in clinical practice, switching to a second thiopurine proved to be a valid strategy. Tight monitoring of elderly IBD patients switching to a second thiopurine because of adverse events is recommended.

Background Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others. Aims Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date. Methods Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018. Results The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease,p < 0.001), gender (female,p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs. Conclusions One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Background and aims Our objective was to define, describe and organize (on the basis of consensus) the patient's preferences in the management of ulcerative colitis (UC), in order to further incorporate them in daily practice and improve patients satisfaction, adherence to the treatment and quality of care. Methods Qualitative study. A narrative literature review in Medline using Mesh and free-text terms was conducted to identify articles on UC patient preferences as well as clinical scenarios that may influence the preferences. The results were presented and discussed in a multidisciplinary nominal group meeting composed of six gastroenterologists, one primary care physician, one nurse practitioner and one expert patient. Key clinical scenarios and patient preferences were then defined, generating a series of points to consider and recommendations. The level of agreement with the final selection of preferences was established following a Delphi process. Results The narrative review retrieved 69 articles of qualitative design and moderate quality. The following key clinical scenarios were identified: diagnosis, follow-up, surgery, and special situations/patients profiles such as adolescents or women. Patient preferences were classified into information, treatment (pharmacological and non-pharmacological), follow-up, relations with health professionals, relations with the health system and administration. Finally, 11 recommendations on patient preferences for UC in relation to its management reached the level of agreement established. Conclusion The consensual description of patient's preferences contribute to identify different areas for improvement in healthcare practice.

Introduction Ustekinumab, a monoclonal antibody that blocks interleukins 12/23, has proven in clinical trials its efficacy in inducing and maintaining clinical remission of Crohn's disease (CD). Its effectiveness and safety in actual clinical practice is less known and may differ from trials. Objective To evaluate its effectiveness and safety in clinical practice (intravenous induction pattern essentially), such as induction and over the long term, in patients with CD refractory to biological treatment. Material and methods Multicentre retrospective analysis (6 hospitals in Aragon), which includes all patients (N=69) with CD undergoing treatment with ustekinumab (either with intravenous or subcutaneous induction), who had at least 16 weeks of follow-up. The clinical response or remission has been evaluated at weeks 16, 24, 32 and 48 using the Harvey-Bradshaw index. Results A total of 69 patients have been included, mean age 42 years, 54% men. A percentage of 89.86 (95% CI [0.805, 0.949]) of the patients presented clinical improvement at week 16 (15.95% remission, 73.92% response). In the subsequent follow-up, this response has been maintained. Age (OR 0.95, P=.028) and smoking habits (OR 0.19, P=.027) have been identified by an ordinal regression model as predictors of poor treatment response while the need for biological change due to adverse effect (OR 96, P=.00017) and due to loss of secondary response (OR 7.07, P=.034) have been predictors of good response. No serious adverse effects have been reported that forced them to stop taking ustekinumab. Conclusion Ustekinumab is effective and safe in real clinical practice to achieve induction and maintenance of the response in patients with refractory CD. Tobacco and age have been shown to be predictors of poor response, while the indication for adverse effect to previous biological and for loss of secondary response has been shown to be predictors of good response.

BACKGROUND Thiopurines are the most widely used immunosuppressants in IBD although drug-related adverse events (AE) occur in 20%-30% of cases. AIM To evaluate the safety of thiopurines in elderly IBD patients METHODS: Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine-related AEs registered in the ENEIDA database were compared. RESULTS Out of 48 752 patients, 1888 started thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2-55] vs 32 [IQR 5-82] months; P 60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P

The small intestine is key in the digestion and absorption of macro and micronutrients. The large intestine is essential for the absorption of water, to allow adequate defecation, and to har-bor intestinal microbiota, for which their nutritional role is as important as it is unknown. This article will describe the causes and consequences of malnutrition in patients with inflammatory bowel diseases, the importance of screening and replacement of micronutrient deficits, and the main indi-cations for enteral and parenteral nutrition in these patients. We will also discuss the causes of short bowel syndrome, a complex entity due to anatomical or functional loss of part of the small bowel, which can cause insufficient absorption of liquid, electrolytes, and nutrients and lead to complex management. Finally, we will review the causes, consequences, and management of malnutrition in patients with malignant and benign digestive tumors, including neuroendocrine tumors (present not only in the intestine but also in the pancreas). © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Presentamos el caso de un varón de 71 años con enfermedad de Crohn de larga evolución (A2B2L3), con estenosis de íleon distal que condiciona dilatación de intestino delgado. En tratamiento con golimumab, azatioprina y prednisona. Ingresó por un cuadro de oclusión parcial con evolución lentamente favorable. De manera súbita el paciente presentó mal estado general y dolor abdominal, objetivándose en la exploración crepitación del tejido subcutáneo. Se realizó un escáner urgente que mostró los hallazgos que se presentan a continuación (...)

En la Digestive Disease Week 2016 se han comunicado algunos datos interesantes, aunque de valor muy relativo, sobre un eventual papel de algunos alimentos en la enfermedad inflamatoria intestinal. También se han presentado otros datos epidemiológicos de interés, varios de ellos sobre su historia natural. Algunos trabajos han abordado un aspecto muy necesario para el clínico práctico, como es encontrar factores predictivos individuales. Desafortunadamente, los avances presentados son relativos, a destacar quizá un estudio que sugiere que un parámetro tan sencillo como es la monocitosis, podría ser un claro factor predictor de mala evolución (resultados muy llamativos, pero con muchas limitaciones). Sí hay datos más relevantes sobre la monitorización y optimización de los tratamientos biológicos, buscando su individualización. Disponemos de nuevos estudios sobre niveles de diferentes anti-TNF, vedolizumab e incluso ustekinumab. También se comunicó un trabajo que pretendía estimar la seguridad de los tratamientos anti-TNF según aspectos genéticos (y clínicos) del paciente. Sobre la monitorización de la enfermedad en sí misma, no hay nuevas evidencias que vayan a cambiar nuestra práctica habitual. En la prevención del cáncer de colon, los datos presentados tampoco modificarán nuestra actuación práctica clínica, pero se comunicó un estudio con una novedosa y prometedora estrategia. Se trata del uso de un nuevo panel de ADN en heces, con resultados muy prometedores en la detección de displasia de alto grado o cáncer colorrectal en estos pacientes.In Digestive Disease Week 2016, interesting data were presented on the eventual role of certain foods in inflammatory bowel disease, although the value of these data is relative. Also of interest were epidemiological studies, of which several analysed the natural history of the disease. Some presentations dealt with the search for individual predictive factors, a pressing need in clinical practice. Unfortunately, some of the findings presented were of dubious value. A study suggesting that a simple parameter as increased blood monocytes could be a clear predictive factor of poor outcome could perhaps be highlighted (the results were striking but had multiple limitations). In contrast, more interesting data were presented on monitoring and optimising biological therapy in the search for an individually-tailored approach. New studies were presented on the levels of distinct anti-TNF agents, vedolizumab and even ustekinumab. One study aimed to estimate the safety of anti-TNF agents on the basis of the patient''s genetic (and clinical) features. There is no new evidence that will change our clinical practice. Equally, the data on colon cancer prevention will not modify our clinical practice, although one study reported a promising new strategy, consisting of the use of a new stool DNA test, with very promising results in the detection of high-grade dysplasia or colorectal cancer in these patients.

There are no important new data on the aetiology of inflammatory bowel disease. However, some new data were presented on the possible importance of certain nutrients or drugs in the genesis of the disease, as well as other data related to genetic features and their relationship with the microbiota. A highly interesting study suggested the strong potential of serological studies in predicting the course of Crohn's disease. The value of magnetic resonance imaging and the potential of low-radiation-dose tomography were reaffirmed in the monitoring and follow-up of patients and their treatments. Studies also confirmed the utility confirmed of new (and more comfortable) methods of home measurement of faecal calprotectin levels. In individualized therapy, attempts are being made to increase the practical application of new results on anti-TNF levels and their antibodies, for example, by identifying the utility of non-trough levels. We believe that the results presented on the impact of the disease on patients themselves were especially important, from their own perspective and in diverse setting. This impact is important both for patients (not only because of the repercussions of the disease on their quality of life but also on their mental health, disability, stress, and financial situation, etc.) and for their families. Finally, interesting results were presented of well-performed studies on colorectal cancer prevention in inflammatory bowel disease. These results confirm chromoendoscopy as a key technique but suggest that technological advances could change this situation, thus simplifying prevention.

A lot of data were reported about monitoring patients with inflammatory bowel disease, with varying degrees of practical applicability. Concerning the evaluation of disease activity, it was established that objective assessments are needed. Among the techniques that we use, although endoscopy is undoubtedly the reference standard, a lot of data were presented regarding less invasive techniques. The importance of MRIs, CTs and ultrasounds (with some variations) was thus reiterated. The importance of fecal calprotectin is also reiterated, not only for colon disease, but probably small intestine disease as well. Regarding treatment monitoring, a great deal was reported about anti-TNF therapy, demonstrating again its potential role when properly used. In addition to results with infliximab, results with adalimumab were reported as very consistent. For colon cancer prevention, it seems that the clinical guidelines are achieving their objective. It also seems clear that we must improve conventional endoscopic techniques. Finally, there are other aspects that need to be considered when monitoring our patients, such as adequate sleeping patterns, anxiety or depression.

Multiple data were presented on inflammatory bowel disease (IBD) in Digestive Disease Week (DDW). Of particular interest to gastroenterologists were those on novel treatments and information on safety. Other data, such as those relating to disease "follow-up", were possibly of lesser interest. However, the information reported this year was, in my opinion, highly important, because it could lead to significant changes in clinical practice. Thus, results presented strongly suggest that patients with asymptomatic IBD, specifically Crohn's disease (CD), often develop complications during their clinical course. Moreover, this is especially true in patients with CD and biological signs of inflammation, despite being asymptomatic. In addition, it seems clear that the absence of symptoms does not imply an absence of inflammation. These observations indicate a dual practical message: patients should be followed-up and objectively evaluated. Multiple data were presented on how to objectively evaluate disease activity in IBD. The prognostic value and objectivity of endoscopy has been reaffirmed, specifically with new data on the only validated index, the UCEIS, in ulcerative colitis. Together with endoscopy, the role of less invasive techniques such as imaging tests (magnetic resonance enterography, computed tomography enterography and even echography, with and without contrast agent) and fecal markers has been reaffirmed in several conditions and these techniques have a certain predictive value. Finally, many studies were reported that confirm the therapeutic activity of levels of anti-TNF and its antibodies in certain conditions and with some limitations.

Anti-tumor necrosis factor alpha (TNF-α) agents have been a great advantage in the treatment of inflammatory bowel disease. The safety profile of these agents is well-known and they can be considered safe when properly used. In clinical practice, the most important adverse events are infections. Other adverse effects are also possible but are much less frequent. However, because of the widespread use of these drugs, these uncommon adverse effects may also occur in clinical practice. We report one of these infrequent adverse events, multiple sclerosis, which is rare but important because of its severity. When neurological symptoms appear during treatment with anti-TNF-α, multiple sclerosis must be ruled out. The diagnosis and therapeutic management of this entity, led by a neurologist with our collaboration, required permanent cessation of anti-TNF-α therapy. Azathioprine, interferon, and even natalizumab, may be used as alternatives in patients who require therapy.

Iron is necessary for the normal development of multiple vital processes. Iron deficiency (ID) may be caused by several diseases, even by physiological situations that increase requirements for this mineral. One of its possible causes is a poor dietary iron intake, which is infrequent in developed countries, but quite common in developing areas. In these countries, dietary ID is highly prevalent and comprises a real public health problem and a challenge for health authorities. ID, with or without anemia, can cause important symptoms that are not only physical, but can also include a decreased intellectual performance. All this, together with a high prevalence, can even have negative implications for a community's economic and social development. Treatment consists of iron supplements. Prevention of ID obviously lies in increasing the dietary intake of iron, which can be difficult in developing countries. In these regions, foods with greater iron content are scarce, and attempts are made to compensate this by fortifying staple foods with iron. The effectiveness of this strategy is endorsed by multiple studies. On the other hand, in developed countries, ID with or without anemia is nearly always associated with diseases that trigger a negative balance between iron absorption and loss. Its management will be based on the treatment of underlying diseases, as well as on oral iron supplements, although these latter are limited by their tolerance and low potency, which on occasions may compel a change to intravenous administration. Iron deficiency has a series of peculiarities in pediatric patients, in the elderly, in pregnant women, and in patients with dietary restrictions, such as celiac disease.

Several clinical trials on new therapies in ulcerative colitis were presented in Digestive Disease Week 2010, mostly with negative results. Thus, rituximab (anti CD 20) and MDX-1100 (a chemokine inhibitor) failed to show efficacy, although higher doses of both agents will probably be tested in the future. A probiotic able to synthesize and release interleukin-10 into the gut lumen also failed to prove useful. In contrast, HMPL-004, an extract from a herb used in Oriental medicine, was reported to have positive results in mild-to-moderate colitis. In addition to these data on new therapies, some other results segurion current therapies were also presented. The results communicated on salicylates once again emphasized the importance of compliance to achieve efficacy and the advantages of single-dose regimens in achieving this goal. The data reported on the protective role of salicylates against colon cancer were contradictory. Observational studies of biological agents supported the efficacy of infliximab and controlled preliminary data suggested the utility of adalimumab. Both Spanish observational studies and a poster presenting a blind, controlled trial showed the efficacy of leukocyte apheresis in maintaining remission in steroid-refractory ulcerative colitis. Finally, retrospective and observational Spanish data on beclomethasone supported the usefulness of this drug.

Resumen Objetivo Describir nuestra experiencia con infliximab en el tratamiento de la colitis ulcerosa (CU). Material y metodos Estudio observacional y retrospectivo de pacientes tratados con infliximab por CU, con criterios de corticorresistencia o corticodependencia en dos hospitales de referencia. Se revisan las historias clinicas de todos los pacientes tratados con infliximab, segun la Guia de GETECCU, hasta diciembre de 2006, utilizando los criterios de Lennard-Jones, la clasificacion de Montreal y los criterios de Truelove-Witts. Se evalua la respuesta a las 8 semanas, aunque en la mayoria de los casos hay un seguimiento mayor de 30 semanas. Resultados Se evaluan 19 pacientes (15 corticodependientes y 4 corticorresistentes). El farmaco obtuvo respuesta en 13 de 15 corticodependientes (87%; intervalo de confianza [IC] del 95%, 56-98) y remision en 9 de 15 (60%; IC del 95%, 32-83,7). En 2 pacientes no hubo respuesta con una colectomia. Se observo remision en 2 (50%) de los 4 corticorresistentes, y los otros 2 pacientes fueron sometidos a colectomia. Se observo solo un efecto adverso grave: una neunomiaa cavitada por Pseudomonas aeruginosa en un paciente tratado simultaneamente con azatioprina y prednisona. Discusion Esta experiencia sugiere que infliximab es un farmaco activo en la CU refractaria, aunque su posicion en el esquema terapeutico debe definirse con nuevos estudios.

Introduction Intravenous steroid therapy is the standard treatment in severe attacks of ulcerative colitis (UC), but 20% to 60% of patients fail to respond and require colectomy. Cyclosporine (CyA) has shown efficacy in steroid failures and could avoid surgery, but controversy remains. Aim The objective of this study was to conduct a systematic review to evaluate the effectiveness and safety of CyA in inducing remission in patients with a severe attack of UC. Methods We did a systematic review using Cochrane methodology, including data from published (in English, French, Spanish or German) clinical trials done in adults using intravenous or oral CyA in UC. Data on efficacy are obtained from controlled and observational clinical trials, and for safety issues case reports are also considered. Results 31 studies were identified which met the inclusion criteria, 22 (18 uncontrolled, 4 controlled) with intravenous CyA, and 9 (all uncontrolled) using oral CyA. Only 4 controlled trials (one in abstract form) are available, and only one compares CyA to placebo. However, efficacy results are very consistent in these 4 trials, and very similar to those in observational studies. CyA achieves remission in 91,4% and 71.4% of patients in controlled and uncontrolled studies using intravenous route, and in 71,2% using oral route. Two mg/kg/day seems so efficacious and safer as previous standard 4 mg/kg/day dose. Minor side effects are rather common but do not seriously limit therapy. Severe side effects, specially infections, are uncommon but clinically relevant with several deaths reported. Conclusion CyA (intravenous, 2 mg/kg/day) constitutes an efficacious and relatively safe alternative in the treatment of severe, steroid-refractory, attack of UC. To optimize treatment, the correct selection of patients, a standardized protocol and clinical surveillance are recommended.

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 and aim Evidence-based clinical guidelines on Ulcerative colitis (UC) have been developed through a consensus, while GRADE methodology is the current standard for guideline development. This is the first one based on GRADE methodology on UC. Methods Following GRADE methodology, the Spanish Group of Ulcerative Colitis and Crohn's disease (GETECCU) have developed a guideline on UC treatment. After selection of relevant clinical scenarios, 32 clinical questions were chosen and recommendations were established. Results In 2 questions no recommendation was possible. Twenty-two actions were recommended for, 14 strongly and 8 weakly. However, in 8 questions a recommendation against doing something was obtained, weak in 5 and strong in 3. The majority of recommendations were based on moderate quality evidence, and only 5 on high-quality evidence. Conclusions With GRADE methodology we find a clear recommendation on possible actions in most clinical decisions in UC treatment, but much more clinical high-quality research is needed.

Iron deficiency (ID), with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by enteroscopy.

Background and aim: Infliximab (IFX) has been shown effective both for induction and maintenance of remission in moderate-to-severely active ulcerative colitis (UC). The aim of this retrospective multicenter study is to provide data on short and long-term efficacy and safety of IFX in UC in a "real life" setting. Methods: data were extracted from clinical records of consecutive patients with biopsy proven UC who received at least one infusion of IFX from January 2008 to June 2012 in nine referral centers from Southern Italy. Clinical and demographic characteristics, IFX indications, concomitant medications, disease activity (Mayo score), date of colectomy, and adverse events were registered. Outcomes of efficacy were clinical and endoscopic responses at week 14 and 52, steroid-free remission, mucosal healing and colectomy rate. Result: The study included 257 adult patients with UC (58.4% males, mean age 35.7, range 10-78) treated with scheduled IFX 5 mg/kg. Median duration of UC was 50 months (IQR 18-115), and the extension of disease was pancolitis in 185 (72.0%) subjects, left-sided colitis in 57 (22.2%), and proctosigmoiditis in 15 (5.8%). Indication to IFX were steroid dependence in 74.7% of patients, steroid-resistance in 23.0%, extra-intestinal complications in 2.3%. Thiopurine failure or intolerance was reported in 40.5%. IFX was used as rescue therapy in 5.8% of patients with severe refractory UC. Patients received a median of 9 infusions (range 1-40) and median follow-up was 26 months. IFX optimization for loss of response was necessary in 39 (15.2%). Overall median Mayo score was 9 (IQR 7-10) at enrolment, 5 (IQR 2-6) at 14 weeks and 3 (IQR 1-5) at 52 weeks (p,0.001 by Anova). Remission rates were 32% at week 14, 39.4% at week 52. The rate of patients able to stop steroids were 42.0% at 14 weeks and 40.5% at 52 weeks. Mucosal healing was obtained in 56.7%. Colectomy was performed in 22 patients (8.6%). Median time to colectomy was 7.1 months. Adverse events were observed in 51 (19.8%) of patients: 20 infusion reactions, 22 opportunistic infections (7 patients with shingles). Four subjects developed "de novo" neoplasia (2 colo-rectal carcinoma). Conclusion: This is the first report of a large open-label multicenter Italian series in "daily clinical practice". Infliximab is a safe and effective treatment in avoiding colectomy and inducing both short and long-term clinical response and mucosal healing in moderate-to-severe UC.