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Background Background: The feasibility of anti-TNF discontinuation in inflammatory bowel disease (IBD) must be proven in clinical trials including patients in clinical, endoscopic, and radiologic remission at the time of anti-TNF withdrawal to make recommendations for clinical practice. Aims Primary: to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment vs. those who continue treatment. Secondary objectives: to know the effect of anti-TNF withdrawal on relapse-free time, mucosal healing and safety; and to identify predictive factors for relapse. Methods Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis (UC) or Crohn’s disease (CD) in clinical remission for > 6 months were randomised to maintain anti-TNF treatment [maintenance arm (MA)] or to withdraw it [withdrawal arm (WA)]. Patients who were on infliximab (IFX) received IFX 5 mg/kg or an intravenous placebo every 8 weeks, while patients on adalimumab (ADA) received subcutaneous ADA 40 mg or placebo every other week. Patients were followed-up until month 12 or up to the time of clinical relapse, whichever came first. Inclusion and exclusion criteria, trial scheme and definitions are summarized in figures 1a, 1b and 1c. Results were analysed by intention-to-treat (ITT) and by per-protocol (PP). Local investigators were blinded to faecal calprotectin (FC) and IFX and ADA trough levels. On-site monitoring was performed to assess data quality. Results 159 patients were screened, from whom 140 were randomised and comprised the ITT cohort: 70 allocated to the MA and 70 to the WA. Fifteen patients dropped out before the end of follow-up (12 months or relapse), leaving 63 patients in the MA and 62 patients in the WA for the PP analysis. The characteristics of patients in the MA and WA were similar (figure 2). The proportions of patients who maintained clinical remission -59/70 (84%), 95% confidence interval (CI)=74-92% in the MA vs. 53/70 (76%), 95%CI=64-85% in the WA- and who remained without significant endoscopic lesions at the end of follow-up were similar between groups (figures 3a, 3b, 3c). Only the proportion of patients with FC >250 mg/g was higher in the WA at the end of follow-up (figure 3d). Maintenance of clinical remission was no different between groups (figure 4). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar between groups (4% in MA vs. 7% in WA). Conclusion Anti-TNF withdrawal in selected IBD patients in clinical, endoscopic, and radiologic remission could be feasible without an increase in the risk of clinical relapse. Long-term follow-up of these patients is warranted.

La esofagitis eosinofílica (EoE) es una enfermedad inmunoalérgica crónica causada, en la mayoría de los casos, por una alergia alimentaria no IgE mediada. Su prevalencia actual es superior a 1 caso por cada 1000 habitantes en España y Europa, mientras que es emergente en el continente sudamericano. Esta revisión trata de actualizar las novedades terapéuticas aparecidas en los últimos 5 años para inducción y mantenimiento en esta patología, incluyendo la aparición de nuevos fármacos antiácidos (inhibidores del ácido competitivos del potasio), la simplificación de los esquemas dietéticos, la aparición de nuevos corticoides deglutidos diseñados específicamente para el tratamiento tópico, así como la incorporación de fármacos biológicos al algoritmo terapéutico de la enfermedad. La dilatación endoscópica continúa siendo un complemento eficaz y seguro para la mejoría sintomática, en combinación con tratamientos antiinflamatorios de la enfermedad.

Background There is scarce information about Crohn’s disease (CD) affecting oesophagus, stomach and duodenum. The aim of the study was to describe phenotypic features, disease course and treatment response in these patients. Methods Patients with CD and upper involvement (oesophagus, stomach and/or duodenum) were included (upper CD=UCD). Extensive CD (ECD) was defined as concomitant distal involvement (jejunal, ileal and/or colonic). A multicentric, longitudinal and retrospective study was designed to evaluate disease characteristics at diagnosis and behaviour of UCD in patients >= 18 years between January 2000 and December 2019 with at least 1 year follow-up since diagnosis. All treatments for UCD diagnosis and reason to start them were recorded, as well as 14- and 52-week response. Incidence of malignancy was also evaluated. Descriptive statistics were applied for quantitative and qualitative variables. Exact Fisher test was used for comparison of proportions. Results 197 (0.9%) UCD among 21.670 patients with Crohn’s Disease (CD) from 28 Spanish centres were included with a median of 10.7 years follow-up (min 2.2– max 22.1). Nearly 55% were men: median age at CD diagnosis was 29 years whereas for UCD was 32 years, with a mean of 2 months between CD and UCD diagnosis (SD 0.4). Only 9 patients had isolated UCD, whereas the rest presented ECD. 97% were diagnosed by endoscopy, in 2/3 due to symptoms (epigastric pain and dyspepsia). Inflammatory phenotype was prevalent in UCD with aphthous ulcer as the main endoscopic lesion (42%). Isolated duodenal location was the most frequent, followed by the antrum. Systemic corticosteroids and thiopurines were the most used treatments after UCD diagnosis. Treatment response at 14- and 52-weeks is detailed in Figures 1 and 2. Treatment withdrawal due to UCD activity was seen in 2-11% of patients. Thiopurines was the most durable treatment (median 50 months, min 0–max 210) followed by infliximab and adalimumab. Ten patients presented phenotype change over time (90% from inflammatory to stricturing). 53% of patients underwent endoscopic control (44% due to symptoms). De novo metaplasia was detected in 3 patients, and low-grade visible dysplasia in one. Two patients developed neoplasia: 1 gastric MALT lymphoma and 1 oesophagus carcinoma 5.5 and 20 years after UCD diagnosis, respectively. Conclusion UCD in adult population is infrequent. Upper involvement does not have an impact on immunosuppressive treatment requirements, but extensive disease does, appreciating a similar response to treatments for proximal and distal disease, both in the short and medium term. Although rare, risk of malignancy in UCD exists.

Cow's milk protein is the main food trigger for eosinophilic oesophagitis (EoE) in children and adults and should be continuously avoided once identified as such.To evaluate tolerance of sterilised cow's milk (boiled instead of UHT processing) with regard to maintenance of EoE remission, health-related quality of life (HRQoL), nutritional intake and allergic sensitisation in patients of all ages with milk-triggered EoE METHODS: We prospectively recruited patients in whom cow's milk was demonstrated to trigger EoE after an empirical food elimination diet-based study. They were given 200 ml of sterilised cow's milk twice daily for 8 weeks. Endoscopic assessment, peak eosinophil counts, oesophageal-related symptoms, HRQoL, blood eosinophils, eosinophil cationic protein (ECP), skin prick test and serum total and specific immunoglobulin E (IgE) to major milk proteins were monitored before and after sterilised milk intake.Eighteen patients (13 male) in EoE remission underwent a sterilised milk challenge. Twelve maintained EoE remission (15 eos/hpf) while EoE recurred in the remainder. Endoscopic appearances deteriorated in non-tolerant patients. HRQoL scored well at baseline and was maintained among patients tolerant to sterilised milk, but deteriorated in reactive ones. No significant changes in blood eosinophil count, ECP, tryptase or total and milk-specific IgE serum levels were observed from baseline. However, cow's milk-specific IgE increased slightly in non-tolerant patients. Clinical and histological remission were maintained in patients who regularly consumed sterilised milk for 1 year.Sterilised milk did not trigger EoE in two-thirds of patients with documented milk-induced EoE, in either the short or long term.

Background: A novel budesonide orodispersible tablet (BOT) has been proven effective in adult patients with active eosinophilic oesophagitis (EoE) in a 6-week placebo-controlled trial (EOS-1). Aims: To report the efficacy of an open-label induction treatment with BOT in a large prospective cohort of EoE patients within the EOS-2 study. Methods: Patients with clinico-histological active EoE were treated with BOT 1 mg BID for 6 weeks. The primary endpoint was clinico-histological remission (≤2 points on numerical rating scales [0–10] each for dysphagia and odynophagia, and peak eosinophil count

The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease.Adult patients with CD-related fistulae who received at least one biologic agent for this condition from the prospectively-maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic or periostomal fistulae. The primary endpoint was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses.A total of 760 patients from 53 hospitals (673 receiving anti-TNFs, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (IQR, 26-102), 240 patients required surgery, with surgery rates of 32%, 41%, 24% among those under anti-TNF, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, while non-smokers, and combination therapy with an immunomodulator reduced this risk.Biologic therapy is beneficial in approximately three quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one third still undergo surgery due to refractory disease. Some patient and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Background Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis. Methods We conducted a three-part, phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (Part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo (Part B) up to week 24. Eligible patients who completed Part A or Part B continued the trial in Part C, in which those who completed Part A received dupilumab at a weekly dose of 300 mg up to week 52 (the Part A-C group); Part C that included the eligible patients from Part B is ongoing. The two primary end points at week 24 were histologic remission (≤6 eosinophils per high-power field) and the change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score (range, 0 to 84, with higher values indicating more frequent or more severe dysphagia). Results In Part A, histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo (difference, 55 percentage points; 95% confidence interval [CI], 40 to 71; P

ObjectiveTo evaluate the use, effectiveness and safety ofHelicobacter pyloriempirical rescue therapy in third and subsequent treatment lines in Europe.DesignInternational, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis.ResultsOverall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained ConclusionEmpirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update.Trial registration numberNCT02328131.

Background & Aims: There are no studies or recommendations on optimal monitoring strategies for patients with eosinophilic esophagitis (EoE). Our objective was to develop guidance on how to monitor patients with EoE in routine clinical practice, on the basis of available clinical evidence and expert opinion. Methods: A multidisciplinary, international group of EoE experts identified the following important 3 questions during several consensus meetings: why, by what means, and when to monitor patients with EoE. A steering committee was named, and 3 teams were formed to review literature and to formulate statements for each topic. In a Delphi survey, a level of agreement of ?75% was defined as threshold value for acceptance. In a final conference, results were presented, critical points and comments on the statements were discussed, and statements were rephrased/rewritten if necessary. Results: Eighteen EoE experts (14 adult and pediatric gastroenterologists, 2 pathologists and 2 allergists) with a median of 21.7 years in clinical practice, mostly academic or university-based, completed the Delphi survey, which included 11 statements and a proposed algorithm for monitoring patients with EoE. Each statement attained ?75% agreement. Participants discussed and debated mostly about the statement concerning surveillance intervals for EoE patients with stable disease. Conclusions: It was concluded that effective maintenance treatment probably reduces the development of EoE complications, and regular, structured, and, under certain conditions, individualized clinical follow-up is recommended to assess disease activity while opening a window to monitoring side effects, adjusting therapy, and encouraging adherence to treatment. Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings.

Long-standing inflammation leads to esophageal remodeling with stricture formation in patients with eosinophilic esophagitis (EoE). The ability of proton pump inhibitors (PPI) to reverse endoscopic features of fibrosis is still unknown.To investigate the effect of a short course of PPI treatment in reducing endoscopic findings indicative of esophageal fibrosis in EoE patients.Cross-sectional analysis of the EoE CONNECT registry. Patients who received PPI to induce EoE remission were evaluated. Endoscopic features were graded using the EoE Endoscopic Reference Score (EREFS), with rings and strictures indicating fibrosis. Results were compared to those from patients treated with swallowed topic corticosteroids (STC).Clinico-histological remission was achieved in 83/166 adult patients treated with PPI (50%) and in 65/79 (82%) treated with STC; among responders, 60 (36%) and 57 (72%) patients respectively achieved deep histological remission (5 eosinophils/hpf). At baseline, mean±SD EREFS was lower in patients treated with PPI compared to those who received STC (p 0.001). Short term treatment significantly reduced EREFS scores in patients treated either with PPI or STC as well as rings and strictures. Among patients treated with PPI, deep histological remission (5 eosinophils/hpf) provided further reduction in total EREFS score.Effective PPI therapy for EoE significantly reduced endoscopic esophageal fibrosis in the short term.

Background Swallowed topical corticosteroids (STC) are a first-line treatment for eosinophilic esophagitis (EoE) but are not uniformly effective. Dupilumab (DPL), a fully human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 inflammation. In Parts A and B of the phase 3 LIBERTY-EoE-TREET (NCT03633617) study, weekly DPL 300mg improved clinical, symptomatic, histologic, and endoscopic aspects of EoE and was generally well tolerated in adult and adolescent patients (pts) with EoE. Purpose To assess the efficacy of weekly DPL 300mg vs placebo (PBO) at Week 24 in pts from Parts A and B with/without prior history of STC use, and from Part B with/without a history of inadequate response, intolerance, or contraindication to STCs. Method Pts who received STCs for EoE within 8 weeks prior to baseline were excluded from the study. Co-primary endpoints at Week 24 were the proportion achieving peak eosinophil count (PEC) ≤6/high-power field (hpf) and the absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Other secondary endpoints at Week 24 included: % change in PEC; absolute change in Histologic Scoring System (HSS) grade and stage scores and Endoscopic Reference Score (EREFS); % change in DSQ score. Result(s) At baseline, in Parts A and B combined, 84/122 (69%) and 87/118 (74%) of DPL- and PBO-treated pts had history of STC use. For pts treated with DPL vs PBO PEC≤6/hpf was achieved by 59.5% vs 3.4% of pts with, and 57.9% vs 12.9% without, prior STC use. Difference vs PBO (95% CI) in the absolute change in DSQ score was −13.27 (−18.03, −8.50) vs −5.21 (−12.41, 2.00) for pts with/without prior STC use. Difference vs PBO (95% CI) for pts with/without prior STC use were: % change in PEC −80.76 (−97.77, −63.75)/−84.87 (−112.16, −57.58); absolute change in EoE-HSS grade −0.77 (−0.87, −0.66)/−0.57 (−0.77, −0.38) and stage −0.77 (−0.87, −0.66)/−0.55 (−0.73, −0.36); absolute change in EREFS −3.86 (−4.70, −3.02)/−2.59 (−4.16, −1.02); % change in DSQ −34.5 (−47.75, −21.22)/-14.9 (−35.21, 5.36). DPL was generally well tolerated in the intent-to-treat population; the most common TEAEs for DPL/PBO were injection-site reactions (37.7/33.3%). In Part B, 38/80 (48%) and 39/79 (49%) of DPL- and PBO-treated pts had inadequate response/intolerance/contraindication to STCs. For DPL vs PBO PEC≤6/hpf was achieved by 55.3% vs 7.7% with, and 61.9% vs 5.0% of pts without, inadequate response/intolerance/contraindication to STC. Difference vs PBO (95% CI) for absolute change in DSQ score was −11.55 (−19.06, −4.04)/−7.08 (−13.75, −0.42) for pts with/without inadequate response/intolerance/contraindication to STCs. Conclusion(s) Conclusion: Regardless of prior STC use, in this pooled analysis from Part A and Part B of the EoE TREET Phase 3 Study, weekly DPL 300mg demonstrated substantial improvements in clinical, histologic, and endoscopic study endpoints at Week 24 in adults and adolescents with EoE. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest A. Bredenoord Shareholder of: SST, Grant / Research support from: Bayer, Nutricia, SST, Consultant of: Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, Dr Falk, EsoCap, Gossamer Bio, Laborie, Medtronic, RB Pharma, Regeneron Pharmaceuticals, Inc., Robarts Clinical Trials, E. Dellon Grant / Research support from: Research funding; Adare Pharma Solutions, Allakos, GSK, Meritage Pharma, Miraca Life Sciences, Nutricia, Receptos/BMS, Regeneron Pharmaceuticals, Inc., Shire. Educational grant; Allakos, Banner Pharmaceuticals, Holoclara, Consultant of: Abbott, Adare Pharma Solutions, Aimmune Therapeutics, Alivio Therapeutics, Allakos, Arena Pharmaceuticals, AstraZeneca, Banner Pharmaceuticals, Biorasi, Calypso Biotech, Enumeral, EsoCap, Gossamer Bio, GSK, Receptos/BMS, Regeneron Pharmaceuticals, Inc., Robarts Clinical Trials, Salix Pharmaceuticals, Shire/Takeda, A. Lucendo Grant / Research support from: Dr Falk, Regeneron Pharmaceuticals, Inc., Consultant of: Dr Falk, EsoCap, M. Collins Grant / Research support from: Receptos/BMS, Regeneron Pharmaceuticals, Inc., Shire, Consultant of: Allakos, AstraZeneca, BMS, EsoCap, Regeneron Pharmaceuticals, Inc., Shire, A. Khodzhayev Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., X. Sun Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., K. Patel Employee of: Sanofi, B. Beazley Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., A. Shabbir Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc.

Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard. Therapeutic endoscopy in patients with adverse events of EoE may also be required. In particular, dilation may be essential to treat and attenuate progression of the disease in select patients to minimize further fibrosis and stricture formation. Using a modified Delphi consensus process, a group of 20 expert clinicians and investigators in EoE were assembled to provide guidance for the use of endoscopy in EoE. Through an iterative process, the group achieved consensus on 20 statements yielding comprehensive advice on tissue-sampling standards, gross assessment of disease activity, use and performance of endoscopic dilation, and monitoring of disease, despite an absence of high-quality evidence. Key areas of controversy were identified when discussions yielded an inability to reach agreement on the merit of a statement. We expect that with ongoing research, higher-quality evidence will be obtained to enable creation of a guideline for these issues. We further anticipate that forthcoming expert-generated and agreed-on statements will provide valuable practice advice on the role and use of endoscopy in patients with EoE.

Background The safety of ustekinumab in pregnant patients with inflammatory bowel disease (IBD) and in their offspring has been barely studied. Aims Primary: To know the risk of serious adverse events (SAEs) in women exposed to ustekinumab during pregnancy and in their offspring. Secondary: To assess the risk of complications of the mothers and their offspring. To describe the patterns of use of ustekinumab during pregnancy in these patients Methods Patients with IBD exposed to ustekinumab during pregnancy from DUMBO registry of GETECCU were included. DUMBO is a prospective, observational and multicentre registry, which enrols pregnant women with IBD over 5 years in 70 centres in Spain. The registry was kicked off in September 2019. SAE definition was based on “Clinical Safety Data Management: Definitions and Standards for Expedited Reporting by European Medicines Agency”. Study protocol is summarized in figure 1. Results 49 pregnant patients have been exposed to ustekinumab during pregnancy so far (table 1). All pregnancies were singleton. Two patients were lost of follow-up (1st and 2nd trimester) but had uneventful pregnancies up-to last visit. There were 2 miscarriages (4%) at 1st trimester of gestation, 34 newborns and 11 pregnancies that were still on-going at the time of this analysis. All patients were on ustekinumab at conception (57% of them 90 mg/8 weeks). A total of 12 patients (24%) withdrawn ustekinumab during pregnancy: 1 (8%) due to disease flare, 1 (8%) underwent surgery due to intestinal obstruction, 2 (17%) due to patient’s choice (at 1st and 2nd trimester), and 8 (67%) due to clinicians’ decision (1 at 1st, 5 at 2nd and 2 at 3rd trimesters). No patient flared up after ustekinumab discontinuation. 10 (20%) patients had SAEs: 2 miscarriages, 1 intestinal infection, 1 subcorionic hematoma, 3 preterm birth, 1 intestinal obstruction and perforation (underwent surgery), 1 preeclapmsia, and 1 stoma obstruction. A total of 34 women gave birth after a median of 39 weeks gestation [interquartile range (IQR)=38–40], 3 (9%) preterm births, 55% by caesarean section (82% obstetric reasons and 18% perianal fistulae). Of the 34 newborns, 53% were female, median birth weight was 3,110 g (IQR=2,820–3,325), 3 (9%) low-birth weight, and 50% were breastfed exclusively. Median babies’ follow-up was 12 months (IQR=7–16). During follow-up, 3 children (9%) had severe infections (2 urinary infections, and 1 bronchiolitis by respiratory syncytial virus). In addition, 4 (13%) children were hospitalized: 1 cardiorespiratory arrest, 1 prematurity, 1 jaundice, and 1 vesicoureteral reflux Conclusion Ustekinumab seems to be safe during pregnancy in patients with IBD and their offspring.

Background Treatment with thiopurines may be associated with different adverse effects, including acute pancreatitis. Risk factors for developing pancreatitis due to thiopurines in patients with Inflammatory Bowel Disease (IBD) are not clearly identified, with underlying genetic predisposition being a possible cause. Our aim was to evaluate predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. Methods IBD patients treated with thiopurines were identified from the prospectively maintained ENEIDA registry of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU). We included as cases those patients who met the Atlanta diagnostic criteria for pancreatitis and had an imaging test that ruled out biliary origin. We included as controls those patients without pancreatitis after at least two years of treatment with thiopurines. Blood samples were collected, and DNA was extracted from leukocytes for all participants and, subsequently, pooled samples were sequenced. Sequencing of a panel of genes (CASR, CEL, CDLN2, CFTR, CPA1, CTRC, PRSS1, and SPINK1) was carried out in the NextSeq500 platform. Variants detected were classified as pathogenic, variants of unknown significance, and benign according to the American College of Medical Genetics and Genomics (ACMGG) guidelines. Results Ninety-five cases and 105 controls were enrolled, 57% were women. Pancreatitis was diagnosed at a median age of 39±13 years old. No patient had previous history of chronic or acute pancreatitis. There were no differences between thiopurine-treated patients with and without pancreatitis in age, sex, and age at IBD onset. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). Of these 35 variants (12 in cases and 18 in controls), 6 were classified as pathogenic (1 in cases and 5 in controls), belonging to the CEL and CFTR genes, and 30 as variants of uncertain significance (21 in cases and 22 in controls). There were no significant differences between the groups of cases and controls, both in totals and by genes. None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes. None of the analysed samples with pancreatitis carried a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes. One of them was in the CDLN gene in a single patient with pancreatitis, and 3 variants in the CPA1 gene in 5 control individuals. Conclusion In patients with IBD, there is no predisposition to thiopurine-induced pancreatitis associated with genes known to cause pancreatitis.

Background Some patients with Inflammatory Bowel Disease (IBD) who are treated with anti-TNFα therapy develop a drug-induced psoriasis (IP) as an adverse event. There are some therapeutic approaches, being more frequent to change the biologic therapy to ustekinumab, effective and approved for the treatment of both entities. This could be the best option, but available data are lacking and it could increase the risk of IBD relapse. Our aim is to assess the management of anti-TNF IP in IBD, and the subsequent evolution of both diseases in a large nationwide cohort of patients. Methods Retrospective, observational multicenter study from the prospectively maintained Spanish ENEIDA registry. Participants were patients with IBD and anti-TNFα IP. At baseline, psoriasis severity was classified as mild, moderate or severe, and remission was defined as the resolution of skin lesions, clinical response as an improvement without complete resolution, and no response as the absence of improvement. IBD clinical activity was defined based on Harvey-Bradshaw Index and Partial Mayo Score. All items were evaluated when available at baseline and 16, 32 and 54 weeks. Results Anti-TNFα IP was reported in 234 patients (CD: 185, UC: 46, unclassified IBD: 3). SWAP strategy was chosen in 76 patients (32.5%), most of them to ustekinumab (90.8%), 71 (30.3%) patients continued anti-TNF, 49 (20.9%) discontinued it, and in 38 (16.2%) a switch to a second anti-TNF was made. The decision to continue or not anti-TNF was associated to psoriasis severity (p Conclusion Evaluating IBD activity and psoriasis severity is essential before modifying IBD treatment due to IP. Continuing anti-TNF treatment in mild psoriasis cases, and considering SWAP to ustekinumab in moderate-severe ones, could be a suitable strategy.

Background An increased risk of lymphoma has been described in patients with Inflammatory Bowel Disease (IBD). The aims of our study were to determine the clinical presentation of lymphoma, previous exposure to immunosuppressive and biologic therapies, and the management and evolution of lymphomas in patients with IBD. Methods IBD patients with diagnosis of lymphoma from October 2006 to June 2021 were identified from the prospectively maintained ENEIDA registry of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU). Investigators at each participating centre provided additional information on lymphomas. Results We identified 52 patients with lymphoma in 18 centres following 21,740 patients with IBD (2.4 cases of lymphoma/1,000 patients with IBD; 95% CI 1.8-3.1). 35 were men (67%) and 27 (52%) had Ulcerative Colitis. Non-Hodgkin lymphoma was the most common lymphoma (65%). The median age at diagnosis of lymphoma was 59 years old (IQR 48-67). 31 patients (60%) received thiopurines, and 20 (38%) an anti-TNF drug (one of them had not received thiopurines) before lymphoma diagnosis. Age at diagnosis of lymphoma was lower in those patients treated with thiopurines (53 ± 17 years old) and anti-TNF drugs (47 ± 17 years old) than in those patients not treated with thiopurines nor anti-TNF drugs before the diagnosis of lymphoma (63 ± 12 years old; p Conclusion Most IBD patients with lymphoma had been treated with thiopurines and/or anti-TNF agents before lymphoma diagnosis, and these patients were younger at diagnosis of lymphoma than those not treated with these drugs. IBD treatment was usually changed after a diagnosis of lymphoma. Relapse and mortality of lymphoma were not related to the use and duration of thiopurines or biologic therapies.

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON® Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard 13C-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients ≥18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naïve, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT < 0.90, positive ≥ 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON® Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection.

The stool antigen test (SAT) represents an attractive alternative for detection of

To evaluate the use, effectiveness and safety ofInternational, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis.Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed90% of cases. Overall effectiveness remained90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%.Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update.NCT02328131.

Dietary and pharmacological (proton pump inhibitors, swallowed topical corticosteroids) therapies are effective for induction of clinical and histological remission of eosinophilic esophagitis. However, data evaluating their long-term efficacy and safety is limited.Since eosinophilic esophagitis is chronic, clinical, endoscopic, and histological features usually recur when successful treatments are stopped. In untreated patients, persistent esophageal eosinophilic inflammation may progress to fibrostenosis over time, giving place to strictures and narrow-caliber esophagi. This article comprehensively reviews available data on long-term maintenance of eosinophilic esophagitis with pharmacological and dietary treatment. It also discusses limitations re: available literature and outlines data gaps on adherence to therapy and monitoring disease activity in the long-term.Evidence indicates that long-term maintenance therapy may decrease the risk of esophageal stricture, food bolus impaction, and need for dilation in patients with eosinophilic esophagitis. Further knowledge on eosinophilic esophagitis phenotypes is needed to ascertain who will benefit best from sustained therapy. Unanswered questions include an adequate definition for sustained remission, best strategies for maintenance drugs and diets, enhancement of treatment adherence, and proper monitoring for long-term surveillance.

Purpose of review The aim of this review is to highlight recent advances in dietary therapy for eosinophilic esophagitis (EoE). Recent findings An empiric elimination diet step-up strategy is now well established as the initial approach for dietary treatment. The most common food triggers are by far cow's milk, followed by wheat and egg. Legumes seem to be important solely in Spain and other Mediterranean countries, where they are regularly consumed. Retrospective efficacy data on cow's milk elimination diet in children vary from 25 to 65%. The recently described esophageal prick test did not detect local reaction to the most common food triggers described for EoE. Summary Within the step-up approach, the specific food group or groups to be first eliminated and whether if it will depend on the geographical setting and food consumption habits remain unknown. Prospective studies on cow's milk elimination diet in children and adults are definitely warranted. Better food allergy testing, identifying specific antigens involved in each food group, should be developed for an individualized therapy. As for disease prevention, we undoubtedly need to understand why foods we have been consuming since the Neolithic age have caused EoE just over the past few decades.