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Background Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. Aim To evaluate the need for high-dose budesonide (≥6 mg/d) to maintain clinical remission in CC. Methods Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3 ± 1.5 years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9 mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6 mg/d) to maintain clinical remission. Results Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13–32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6–44) was associated with the need for high-dose budesonide in the multivariate analysis. Treatment with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44–97%), allowing for withdrawal from or a dose decrease of budesonide. Conclusions One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6 mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.

Resumen Introduccion Infliximab ha demostrado su eficacia en evitar la colectomia a corto y medio plazo en los pacientes con colitis ulcerosa corticorrefractarios (CUCR). No obstante, existen pocos datos acerca del tratamiento de mantenimiento mas adecuado en los pacientes con CUCR que han respondido al tratamiento de induccion a infliximab. El objetivo del estudio es comparar la evolucion a largo plazo de los pacientes corticorrefractarios que han respondido al tratamiento de induccion a infliximab segun hayan seguido tratamiento de mantenimiento con azatioprina en monoterapia o infliximab. Pacientes y metodos Se seleccionaron los pacientes ingresados en 3 centros entre enero de 2005 y diciembre de 2011 por un brote moderado-grave de CUCR que habian respondido a las 3 dosis de induccion de infliximab sin necesidad de colectomia antes de la semana 22 despues de la primera infusion. Resultados Se incluyeron 22 pacientes, 9 (37%) siguieron tratamiento con azatioprina y 15 (63%) con infliximab. Despues de una mediana de 18 meses de seguimiento, los corticoides se pudieron retirar en todos. De los que siguieron tratamiento con azatioprina, infliximab tuvo que ser reintroducido en 4 (44%). No hubo ninguna colectomia. De los 15 pacientes que siguieron tratamiento con infliximab, este requirio ser intensificado en el 53%, aunque en 9 (65%) pudo retirarse por remision clinica. Cuatro pacientes (16%) requirieron colectomia. Conclusiones Segun los resultados del estudio parece recomendable seguir tratamiento con infliximab, incluso en los pacientes no expuestos previamente a tiopurinas, dada la necesidad de reintroduccion de infliximab si se sigue tratamiento con azatioprina en monoterapia.

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

Background Loss of response (LOR) to tumour necrosis factor antagonists (anti-TNF) occurs in up to 50% of patients with inflammatory bowel disease (IBD). The ability to predict which patients are likely to lose response would allow therapies to be tailored to the patient’s characteristics. Immunogenicity is a common cause of LOR. Recently, a GWAS performed using the PANTS cohort demonstrated that carriage of one or more HLA-DQA1*05 alleles confers an increased risk of immunogenicity to anti-TNF therapy (Sazonovs et al. Gastroenterology 2019). We found that HLA-DQA1*05 carriage also identified patients at increased risk of clinical LOR to infliximab (Guardiola et al. ECCO 2019). The aim of our study was to know if carriage of a HLA-DQA1*05 allele is also associated with secondary LOR to adalimumab (ADA) in patients with Crohn’s disease (CD). Methods This is a retrospective cohort study from a prospectively maintained data base. Patients were included if they had achieved response to ADA. LOR was defined as recurrence or worsening of IBD-related symptoms that required a change or intensification in treatment, hospitalisation or surgery. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Results We included 53 patients with Crohn’s disease, followed up to LOR (n = 31, 58%) or a median of 51 months (IQR 35–74). Forty-five per cent were carriers of an HLA-QA1*05 allele. HLA-DQA1*05 carriage was associated with LOR both, upon univariate analysis (HR 2.1 (95% CI 1.1–4.3), p = 0.04) and upon multivariate analysis, after adjusting for immunomodulators use, smoking status and BMI (HR 2.74 (95% CI 1.2–6.2), p = 0.02) (Figure 1). The cumulative persistence rates of ADA after adjusting for immunomodulators use was significantly lower in HLA-DQA1*05 carriers compared with non-carriers (HR 4 (95% CI 1.2–15.5), p = 0.02) (Figure 2). Conclusion HLA-DQA1*05 carriage is frequent and it is associated with a marked increase in the risk of LOR to ADA. HLA-DQA1*05 may become a clinically meaningful genetic marker that could allow for treatment to be tailored according to the risk of LOR, which is a step towards personalised medicine.

Background AntiTNF therapeutic drug monitoring is currently performed at trough, immediately before drug administration. However, in clinical practice when subcutaneous medications are used, blood extractions often do not coincide with that moment. The aim of this study was to know if adalimumab levels measured between injections are sufficiently similar to trough levels to be used in clinical practice in a similar way. Methods 295 adalimumab level determinations performed at different time points of 99 injection cycles in 55 patients with inflammatory bowel disease (IBD) were included in the study. 51 patients received 40mg every 2 weeks and 4 patients received 80mg every 2 weeks. Results Median adalimumab levels (IQR) at trough, between days 1–4, 5–8 and 9–13 were 10.6 (6–12), 12.3 (7–18), 13 (7–19) and 10.8 (8–12), respectively. The median differences between trough level and days 1–4, 5–8 and 9–13 were 1.7 (IC 95% 1–2.3) (p < 0.001), 2.3 (IC 95% 1.5–3.1) (p < 0.001), 0.6 (IC 95% –0.2–1.3) (p = 0.13), respectively. Conclusion Adalimumab levels between days 9 and 13 from drug injection are very similar to trough level and could be interpreted clinically at the same way. Adalimumab levels between days 1 and 8 are significantly higher, although, differences are small.

BACKGROUND: Histological remission has been proposed as a new treatment goal in patients with ulcerative colitis (UC) although no universal definition for microscopic activity exists. AIM: We evaluated the accuracy of histological activity to predict clinical relapse in UC patients with both clinical and endoscopic remission. METHODS: Asymptomatic UC patients in endoscopic remission (Mayo endoscopic sub-score 0 or 1) undergoing surveillance colonoscopy in two referral hospitals were prospectively recruited. All colonic biopsies were analyzed according to the Geboes' score (GS) and the presence of basal plasmacytosis (BP). RESULTS: Ninety-six patients were included (38% women, median (interquartile range) age 50.0 (39.0-58.5) years, median disease duration 12.0 (6.5-19.5) years). Histological activity defined as GS ≥ 2B.1, GS ≥ 3.1, or BP was present in, respectively, 26%, 23% and 12%. Within 12 months from index endoscopy, 23% of the patients presented with clinical relapse. In multivariate analysis, active histological disease was the only risk factor predicting clinical relapse (odds ratio (95% confidence interval) 4.29 (1.55-11.87); p = 0.005 for GS ≥ 2B.1 and 4.31 (1.52-12.21); p = 0.006 for GS ≥ 3.1). CONCLUSIONS: In patients with UC in clinical and endoscopic remission, histological activity is an independent risk factor for clinical relapse. Further prospective studies need to clarify whether treatment optimization is justified in this context. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:6 issue:5 pages:765-772 ispartof: location:England status: published

European health systems have developed referral guidelines for the selection of patients for the urgent investigation of suspected colorectal cancer.To evaluate whether quantitative faecal immunochemical testing performs better than commonly used high-risk symptoms based strategies for fast-tracking cancer referrals.We prospectively studied 1054 symptomatic patients referred for a colonoscopy who provided a sample for faecal immunochemical testing. The usefulness of faecal immunochemical testing and two current guidelines for urgent referral were compared for their efficacy in the detection of colorectal cancer and advanced neoplasia.The guidelines detected 46.7% and 43.3% of cases of colorectal cancer while faecal haemoglobin concentration ≥15μg Hb/g detected 96.7% of cases. The diagnostic accuracy of both the guidelines and faecal haemoglobin concentration ≥15μg Hb/g for the detection of advanced neoplasia was: sensitivity 38.3%, 36.1%, 57.1% and specificity 71.8%, 69.5%, 86.6%, respectively. Male gender (OR 2.35; p0.001), age (1.34; p=0.002), and faecal haemoglobin concentration ≥10μg Hb/g (7.81; p0.001) were independent predictive factors of advanced neoplasia.A faecal immunochemical test based-strategy performs better than current high-risk symptoms based strategies for fast-tracking cancer referrals. A score that combines gender, age and a faecal immunochemical test could accurately estimate the risk of advanced neoplasia.

Background & Aims Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. Methods We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Results Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136–696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30–172 μg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Conclusions Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin.

The aim of our work was to test the usability of fecal calprotectin (FC) home-based test in inflammatory bowel disease (IBD) patients. Methods IBD patients were prospectively recruited. They had to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over an 8 weeks period. They had to fill in a usability questionnaire at the first and the last FC measurement. A System Usability Scale (SUS: 0–100) and the Global Score of Usability (GSU: 0–85) were calculated. FC was also centrally measured by ELISA. Results Fifty-eight patients were recruited. Forty-two performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) SUS (0–100) at the first and last use were 85 (78–90) and 81 (70–88), respectively; the median (IQR) GSU (0–85) at the first and last use were 74 (69–80) and 77 (68–83), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The intra-class correlation coefficient between home-based and centrally measured FC was 0.88. Conclusion The adherence to home-based measurement of FC was fair. Usability scores for the home-based test were high. There was a good correlation with the centrally measured FC by ELISA.

Background Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. Aim To develop an evidence-based clinical practice guide on MC current concepts. Methods Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. Results Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. Conclusions This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence.

Background and aim: Intravenous corticosteroids remain the first line therapy for severe attacks of ulcerative colitis although up to 30-40% of patients do not respond to treatment. The availability of alternative therapies to colectomy and the knowledge of early predictors of response to corticosteroids should have improved the clinical outcomes of patients with severe refractory ulcerative colitis. The aim of the study is to describe the current need, way of use, and efficacy of rescue therapies, as well as colectomy rates in patients with severe ulcerative colitis flares. Methods: Between January 2005 and December 2011, all patients admitted in three referral centres for a severe ulcerative colitis flare who received intravenous corticosteroids were identified and clinical and biological data were accurately collected. Patients were followed-up until colectomy, death, or date of data collection. Results: Sixty-two flares were included. Initial efficacy of intravenous corticosteroids (mild activity or inactive disease without rescue treatment, at day 7 after starting intravenous corticosteroids) was achieved in 50% of flares, and rescue therapies were used in 27 episodes (43%). After a median follow-up of 18 months, the colectomy rate was 6.5%. Failed oral corticosteroids for the index flare were the only baseline feature that predicted the need for rescue therapy and colectomy. Conclusions: There is a marked reduction in the colectomy rate and an increased use of medical rescue therapies as compared to historical series. Patients worsening while on oral corticosteroids for a moderate flare are at high risk of rescue therapy and colectomy and, therefore, should be directly treated with rescue therapies instead of attempting intravenous corticosteroids. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

Summary Background Idiopathic bile acid malabsorption (BAM) has been suggested as a cause of chronic watery diarrhoea, with a response to colestyramine in 70% of patients. However, the efficacy of this drug has never been investigated in placebo-controlled trials. Aim To evaluate the efficacy of colestyramine as compared with hydroxypropyl cellulose in the treatment of functional chronic watery diarrhoea. Methods Patients with chronic watery diarrhoea were randomly assigned to groups given colestyramine sachets 4 g twice daily (n = 13) or identical hydroxypropyl cellulose sachets (n = 13) for 8 weeks. The primary end-point was clinical remission defined as a mean of 3 or fewer stools per day during the week before the visit, with less than 1 watery stool per day. A secondary end-point was the reduction in daily watery stool number. SeHCAT test was performed in all patients, but an abnormal test was not a prerequisite to be included. Results All included patients had a SeHCAT 7-day retention ≤20%. There were no statistical differences in the percentage of patients in clinical remission at week 8 between colestyramine and hydroxypropyl cellulose with either intention-to-treat (53.8% vs. 38.4%; P = 0.43) or per-protocol (63.6% vs. 38.4%; P = 0.22) analyses. However, the mean per cent decrease in watery stool number was significantly higher with colestyramine than with hydroxypropyl cellulose (−92.4 ± 3.5% vs. −75.8 ± 7.1%; P = 0.048). The rate of adverse events related to study drugs did not differ between groups. Conclusions Colestyramine (4 g twice daily) is effective and safe for short-term treatment of patients with chronic watery diarrhoea presumably secondary to BAM. Clinical Trials Register number EudraCT 2009-011149-14.

Background: The short-term efficacy of infliximab (IFX) and cyclosporine A (CsA) in steroid-refractory ulcerative colitis (SRUC) has been recently shown to be similar, but long-term outcomes are still unclear. Moreover, the need for further rescue therapies in patients treated with IFX or CsA for SRUC has not been reported. The aims of our study were to compare short-term and long-term efficacy between 2 different strategies based on initial treatment with CsA or IFX for SRUC attacks. Patients and Methods: Between January 2005 and December 2011, all patients admitted for SRUC who required medical rescue therapy were identified from the electronic databases of 3 referral centers and grouped according to whether they received CsA or IFX as first-line rescue therapy, and retrospectively reviewed. Results: Among 50 SRUC attacks, 20 were treated with CsA as first-line rescue therapy and 30 with IFX. The CsA group had a higher proportion of patients with severe UC activity immediately before rescue therapy (P = 0.03) and a shorter median time from intravenous corticosteroids to rescue therapy (P = 0.03). A higher proportion of patients in the CsA group received second-line drug therapy (switch) as compared with the IFX group (P = 0.04). Fifteen patients (30%) were colectomized during the study period, with no between-group differences. Previous thiopurine exposure (P = 0.004; odds ratio 6.1 [1.7-20.9]) was the only independent predictor of colectomy. Conclusions: CsA- and IFX-based strategies for SRUC seem similarly effective in preventing colectomy in the short and long term, although second-line drug therapy is more often required with CsA-based strategies.

Background: Oral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis (UC). In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy. Aim: To evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not. Methods: All episodes of active UC admitted to three university hospitals between January 2005 and December 2011 were identified and retrospectively reviewed. Only moderately active episodes treated with intravenous corticosteroids were included. Treatment outcome was compared between episodes which failed to outpatient oral corticosteroids for the index flare and those directly treated by intravenous corticosteroids. Results: 110 episodes were included, 45% of which failed to outpatient oral corticosteroids (median dose 60 mg/day [IQR 50-60], median length of course 10 days [IQR 7-17]). Initial response (defined as mild severity or inactive disease at day 7 after starting intravenous corticosteroids, without rescue therapy) was achieved in 75%, with no between-group differences (78% vs. 75%). After a median follow-up of 12 months (IQR 4-24), 35% of the initial responders developed steroid-dependency and up to 13% required colectomy. Unsuccessful response to oral corticosteroids was the only factor associated with steroid-dependency in the Long term (P = 0.001). Conclusions: Intravenous corticosteroids are efficient for inducing remission in moderately active UC unresponsive to oral corticosteroids, but almost half of these patients develop early steroid-dependency. Alternative therapeutic strategies should be assessed in this clinical setting. (C) 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Phenotypic Characteristics and Use of Therapeutic Resources in Elderly-Onset Inflammatory Bowel Disease: A Multicentre, Case-Control Study Miriam Manosa, Margalida Calafat, Ruth de Francisco, Carmen Garcia Caparros, Maria Jose Casanova, Patricia Huelin, Marta Calvo, Luis Fernandez Salazar, Miguel Minguez, Alexandra Ruiz-Cerulla, Yamile Zabana, Guillermo Bastida, Joaquin Hinojosa, Lucia Marquez, Manuel Barreiro-de Acosta, Xavier Calvet, David Monfort, Rosario Gomez, Esther Rodriguez, Jose Maria Huguet, Maria Rojas-Feria, Daniel Hervias, Ramon Atienza, David Busquets, Eva Zapata, Carmen Duenas-Sadornil, Mara Charro, Francesc J. Martinez-Cerezo, Rocio Plaza, Juan Maria Vazquez Moron, Javier P. Gisbert, Eduard Cabre, Eugeni Domenech

P170 Planar radiolabelled white cell scintigraphy and Technetium-99m-HMPAO labeled leukocyte single photon emission computed tomography (SPECT) for assessing endoscopic remission in ulcerative colitis C. Arajol1 *, O. Puig Calvo2, F. Rodriguez-Moranta1, L. Rodriguez-Alonso1, A. Ruiz-Cerulla1, T. Lobaton1, A. LopezGarcia1, J. Martin-Comin2, J. Guardiola-Capon1. 1Bellvitge University Hospital, Gastroenterology, Barcelona, Spain, 2Bellvitge University Hospital, Nuclear Medicine, Barcelona, Spain