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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.

Background Crohn’s disease (CD) is an inflammatory bowel disease (IBD) of complex etiology that normally requires bowel resection. However, many patients suffer from post-operative recurrence (POR) within one year. Here, the inflammatory and bacterial influence of the affected intestine transforms the neighboring mesenteric tissue to creeping fat (CrF). The main objective has been to characterize the immune-metabolic profile of CrF according to the POR severity and compare them with mesenteric tissues from IBD-free controls (colorectal cancer and severe obesity). Methods POR severity was classified using the Rutgeerts index: non-recurrents (i0+i1, n=18; NR), mild-recurrents (i2, n=14; MR) and severe-recurrents (i3+i4, n=10; SR). The CrF were gathered from intestinal resections, and IBD-free mesenteric tissues were collected from intestinal resections for colorectal cancer (n=10) and bariatric surgery for severe obese patients (n=11). The total DNA was quantified using DABA assay, 105 cytokines were semiquantified by immune blotting and the fatty acid (FA) profile was quantified by GC-MS. Results The DNA analyses in the CrF showed a major cellularity demonstrating the hyperplasia. When compared to the control groups and to SR, the NR patients showed an increment of infection pro-resolutive cytokines (IFN-γ, MIF, BAFF), and, specially, an increase in both Th1 and Th2 cytokines (IL-18, IL-33). Here, there was also an increase in molecules related to angiogenesis (endoglin) and cellular adhesion (ICAM-1 and VCAM-1). On the other hand, the SR showed a higher level of pro-fibrotic PAI-1 and of the leukocyte homing inducer CCL5. Going into the FA, in comparison to the control groups, there was an increase in the saturated in front of a decrease in mono-unsaturated FA in all the CD groups. Regarding the polyunsaturated FAs, the CrF and the obese mesentery showed a general increase of the omega 6/omega 3 FA ratio when compared to colorectal cancer controls. Finally, both obese and NR CD patients had less short-chain FAs, specifically acetate and propionate, than the colorectal controls. Unexpectedly, the butyrate levels were very low in all the mesenteric tissues. Conclusion The CrF from NR CD patients show an infection resolutive profile regarding the controls and the SR. Instead, these lasts showed signs of chronic inflammation and a fibrotic profile. In general, CrF FA proportions suggests changes in cell signaling due to loss of cell membrane fluidity. In addition, the greater presence of omega-6 than omega-3 FA in the CrF and mesentery of obese patients could be related to the generation of potent proinflammatory lipid mediators. In contrast, the propionate and acetate decrease detected in NR CD patients could be protective against POR.

Background Main aim: To evaluate the retention rate of ustekinumab compared to vedolizumab in Crohn’s disease patients who failed anti-TNF therapy in clinical practice. Secondary aims: To compare the short-term and long-term effectiveness, and the safety of both treatments. Methods Crohn’s disease patients who had received either vedolizumab or ustekinumab after failure or intolerance to anti-TNF agents from ENEIDA registry were included. ENEIDA is a prospectively maintained database promoted by GETECCU. A total of 755 patients from 30 centres were included at time of data extraction. Clinical activity was classified based on Harvey-Bradshaw index both at short (during induction) and in the long-term. Kaplan-Meier curves, Cox regression models, inverse probability weighting and propensity matching score analyses were performed to compare both drugs and to identify predictive factors of treatment effectiveness and durability. Results 755 patients were included (195 in the vedolizumab cohort and 560 in the ustekinumab cohort). After a median of 20 months (IQR 7.4–30) of follow-up, the survival rate for ustekinumab therapy was higher than vedolizumab (Figure 1). The propensity matching score verified the differences between both therapies. The short-term proportion of patients on clinical remission, steroid-free remission and clinical response was also superior in the ustekinumab cohort (Figure 2). In the long-term, significant differences were observed 2 years after the beginning of the treatments, although no differences in clinical response and remission rates were detected in patients who achieved clinical response at week 16 between both cohorts. Vedolizumab was discontinued in 142 patients and ustekinumab in 185, mainly due to primary non-response (52% in the vedolizumab and 58% in the ustekinumab cohort) and loss of response (34% and 25%, respectively) despite the fact that 35% of the patients required intensification. The predictive factors associated to the discontinuation of the therapy are described in table 1. Adverse events were observed, overall, in 12% of the patients, without differences between both groups (Table 2). Following the discontinuation of the treatment with vedolizumab/ustekinumab, other biologic agents were prescribed in 56% of the patients, and 27% underwent surgery. Conclusion In clinical practice, a relatively high proportion of Crohn’s disease patients who received ustekinumab or vedolizumab for anti-TNF failure, maintained these drugs in the medium-long term, although ustekinumab retention rate was higher in comparison with vedolizumab.

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 The use of ustekinumab (UST) and vedolizumab (VDZ) as first line therapy for inflammatory bowel disease (IBD) is increasing due to safety reasons and contraindications of anti-TNFs. However, there are no studies evaluating their efficacy and safety in clinical practice under these circumstances. Thus, our aims were to describe bionaïve patients’ characteristics starting VDZ or UST and to evaluate treatment persistence of these drugs and their safety profile in this scenario. Methods Descriptive, retrospective and multicenter study based on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD –GETECCU). All IBD patients never exposed to biological agents who started VDZ or UST as first-line biological treatment were identified. Results Out of 29,450 IBD patients ever exposed to biological drugs included in the ENEIDA registry, 924 patients met the inclusion criteria. Of these, 366 (40%) started UST and 558 (60%) VDZ as first line biological therapy. UST group: 48% women, 90% Crohn's disease (43% ileal; 13% colic; 43.5% ileocolic; 31% upper gastrointestinal involvement; 25% stricturing behaviour; 12% penetrating, 18% perianal disease), 10% ulcerative colitis (74% extensive, 17% left-sided, 9% proctitis), 27% had extraintestinal manifestations (EIM). Median age at the beginning of UST was 57 years (IQR 57-70), 17% patients had a past history of malignancy and, 34% had associated comorbidities. UST indication was luminal activity except in 2% for perianal disease and 5% for EIM. At the end of follow-up (median 14 months [IQR 6-30]), 12 patients (3.3%) developed adverse effects (AEs) that led to treatment discontinuation in the majority of them (92%). VDZ group: 44% women, 42% Crohn's disease (44% ileal; 18% colic; 38% ileocolic; 25% upper gastrointestinal involvement; 28% stricturing behaviour; 13% penetrating; 7% perianal disease), 58% ulcerative colitis (50% extensive, 42% left-sided, 8% proctitis), 17% had EIM. The median age at the beginning was 61 years (IQR 48-71), 24% had past history of malignancy and, 34% associated comorbidities. The indication was exclusively luminal activity. At the end of follow-up (median 21 months [IQR 8-36]), 36 patients (6.5%) had AEs, that lead to treatment withdrawal in 67% of them (24 patients). Cumulative treatment persistence rates were 78%, 60% and 50% for VDZ and 85%, 75% and 66% for UST at 12, 24 and 36 months, respectively (P Conclusion In clinical practice, VDZ and UST are used first-line particularly in elderly patients with comorbidities. Both treatments have a good safety profile and a high persistence of treatment, being superior for ustekinumab.

Background Mesalazine is the most widely used maintenance therapy for ulcerative colitis (UC). The lowest effective dose recommended is 2g/day, although higher doses are often prescribed. Fecal calprotectin (FC) is a monitoring biomarker that correlates well with endoscopic remission and predicts clinical relapse. Our aim was to evaluate the suitability of mesalazine dose modification based on FC levels in asymptomatic UC patients. Methods Retrospective study in asymptomatic UC patients treated with oral mesalazine therapy which dose was modified in clinical practice according to FC levels between 2016-2022. Sustained clinical remission, clinical relapse and treatment escalation (increase in dose or introduction of rescue therapy) after dose change were assessed during follow-up. Results Mesalazine dose was reduced in 47 patients because of persistent low FC (mean 36ug/g; IQR 22-85); 51% extensive UC, median age of 55 years (IQR 43-63), median duration of clinical remission before dose-reduction 17 months (IQR 8-32) and mean baseline dose 3.2g/day (IQR 2-4). Mesalazine was reduced to 2g/day (IQR 0-2.4). A FC value >250 ug/g was observed at least once in 10% of subjects during follow-up. The cumulative probability of maintaining clinical remission after dose reduction was 90% and 82% at 12 and 24 months, respectively. Rescue therapy was used in 27%, 17% being corticosteroids. In 17 patients, mesalazine dose was increased due to high FC levels (mean 524ug/g; IQR 393-739); 47% extensive UC, median age 54 years (IQR 39-72), median duration of clinical remission before dose increase 16 months (IQR 11-33) and mean baseline dose 2.4g/day (IQR 1.5 -2.4). Dose was increased to 3.2g/day (IQR 3-4.4) and 58% presented FC Conclusion Mesalazine dose modification based on CF levels in asymptomatic patients with UC appears to be a safe strategy and is followed by a low probability of clinical recurrence in the mid-term.

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.

Background Recently, a subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) has been approved for inflammatory bowel disease (IBD). The aims of this study were to evaluate efficacy, safety, pharmacokinetics and patient experience following a switching to SC-IFX in patients who are in clinical remission on IV-IFX maintenance treatment. Methods Multicentre, descriptive, and observational study including Crohn’s disease (CD) and ulcerative colitis (UC) patients who were going to be changed from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD–GETECCU). All patients were on clinical and biological remission at least 24 weeks before changing. Demographic and disease data, clinical activity (Harvey-Bradshaw index for CD and mayo index for UC), analytical data (C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12 and 24 weeks. Results One hundred and fifty-five patients were included: 54 UC (35%) and 91 (65%) CD; 44% women and 56% men; age 45.5 years (32-55). IV-IFX was mainly administered due to active disease (72%) and perianal disease (7%) and during 32 months [range 14-56]. Pre-switch, 78 (50.3%) were on 8-weekly dosing of IV-IFX, 77 (49.7%) were with intensification dose and the half (50.3%) were on concomitant immunomodulatory therapy. SC-IFX was mainly switching by COVID-19 pandemic (60%), to increase through levels (15%) or patient request (25%). The majority of patients (140, 90%) remained with standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 and 240 mg every 2 weeks in 4) and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 and 120 mg every 4 weeks in 3). Clinical indices, CRP levels and FC remained unchanged (Figure). Median SC-IFX levels significantly increased from baseline of 4.5 μg/dl [range 2.6-9.2] to 14 μg/dl [range 9.5-16.2] at week 12 and 13.2 μg/dl [range 10.4-19.7] at week 24. No factors (immunossupresor, body mass index, disease location) were associated with the increase of IFX trough levels. During 24 weeks of follow-up, 16 of the 78 patients (20.5%) stopped immunosuppressant treatment. The adverse events were recorded in 9 patients (5.8%), 4 (2.6%) were hospitalized and 4 (2.6%) had surgery (one of them for perianal disease). Nine patients (5.8%) stopped SC-IFX (1 primary failure, 2 loss of response, 4 adverse events, 1 voluntarily, and 1 surgery). Conclusion The switch from IV to SC IFX maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance. However, the significance of higher drug levels with SC-IFX requires further exploration.

Background Oral corticosteroids remain as the first-line treatment for moderately active ulcerative colitis (UC). In controlled studies, they achieved clinical remission in 30-60% of patients at 30 days. In severe systemic diseases, intravenous bolus administration of methyl-prednisolone accelerates the clinical response and increases the therapeutic efficacy of corticosteroids. Aims To assess the additive effect of IV boluses of methyl-prednisolone in an outpatient Schedule on the remission rate of moderately active UC. Methods Randomized, controlled, open study. Inclusion criteria: 1) moderately active (complete May 6-10) distal or extensive UC; 2) never exposed to immunosuppressants or biologicals; 3) without corticosteroid therapy within the last 6 months. Randomization to oral prednisone 60mg/day (ORAL arm) or the same regimen preceded by intravenous boluses of 500mg methyl-prednisolone for 3 days (BOLUS arm). Primary endpoint: clinical and endoscopic remission at week 8 as defined by a complete Mayo score 1. Results are expressed in frequencies, medians and interquartile range. Results 75 patients (39 ORAL, 36 BOLUS) were included, 24% at diesease onset, 49% extensive UC, 68% were on maintenance with oral 5ASA, and 31% had ever received systemic corticosteroids. At baseline, complete Mayo score was 9 (7-9), with C-reactive protein 9.25 mg/L (3.85-20.17) and fecal calprotectin 1430 ug/g (501-2702), with no differences in the baseline clinical-epidemiological characteristics between both treatment arms. At 8 weeks, 37% of patients achieved clinical-endoscopic remission (47% BOLUS vs 28% ORAL; p=0.089), 52% mucosal healing -Mayo endoscopic subscore Conclusion The addition of three intravenous megaboluses at the beginning of a conventional regimen of oral prednisone achieves a non-significant increase in clinical-endoscopic remission rates at the end of corticosteroid treatment in patients with moderately active UC.

Background Real-world treatment of ulcerative colitis (UC) requires a patient-centric, holistic definition of ‘comprehensive remission' that goes beyond standard regulatory definitions. In an international initiative, we reviewed aspects of UC that affect patients and attempted to achieve consensus on which aspects should be considered in a definition of ‘comprehensive remission’, using a modified Delphi process. This initiative summarized expert consensus recommendations on aspects of UC that are important to patients and that affect their lives, how to measure and score these aspects, and objective markers of mucosal inflammation that are relevant to evaluate in remission, such as endoscopic and histological activity and inflammatory biomarkers. Methods The Delphi consensus panel comprised 10 physicians with expertise in UC and one patient advocate, and two additional physicians chaired the process. To inform the Delphi statements, we asked 18 patients about their experiences of living with UC in remission, asked panel members about their experience of treating patients and systematically reviewed associations between outcome measures in UC. Panel members voted on a 6-point Likert scale in three rounds of anonymous voting, the final round of which was preceded by a live discussion. Consensus was met if ≥ 67% of the panel agreed with the statement (4–6 on the 6-point Likert scale). Statements not meeting consensus in voting rounds 1 and 2 were revised and any not meeting consensus by the end of voting round 3 were discarded (Figure 1). Results The panel agreed that a definition of comprehensive remission should include aspects of UC that are currently measured in clinical trials (blood in stools, stool frequency, disease-related quality of life [QoL], endoscopic remission, histological inflammatory activity, inflammatory biomarkers and discontinuation of corticosteroids), but also additional patient-reported symptoms should be added. These were bowel urgency, abdominal pain, extra-intestinal manifestations, fatigue and sleep disturbance (Table 1). Suggestions for how the severity could be measured and thresholds for remission were agreed for each aspect, with the exception of extra-intestinal manifestations. Disease activity evaluated using ultrasound was voted as important to consider but was not recommended to be included in a measure of comprehensive remission at this stage. Conclusion We used a robust methodology to reach agreement and provide recommendations on the aspects of UC that can be used to define comprehensive remission and assessed in clinical practice. We plan to develop this as a combined measure which may also have applicability in clinical trials.

Background The coexistence of immune-mediated diseases and non-pharmacological immunosuppression states are rare and might determine the natural history of the disease and therapeutic decisions of the physician. IBD guidelines recommend screening for human immunodeficiency virus (HIV) before starting immunosuppressive treatment, but data on the impact of HIV infection on IBD and its management in the era of biological drugs are scarce. Therefore, our aim was to describe IBD phenotype, immunosuppressive requirements, and prevalence of opportunistic infections (OI) in patients with IBD and coexistent HIV infection. Methods Case-control, retrospective, multicenter study including all IBD patients with available HIV serology on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD –GETECCU). IBD patients with positive HIV serology were selected (HIV+) and compared to HIV seronegative IBD patients (controls), matched 1:3 by year of IBD diagnosis, age, gender and type of IBD). Demographic, clinical IBD characteristics, therapeutic requirements, OI and IBD complications were registered. Results Eighty-eight HIV+ IBD patients and 264 controls were included. In the whole cohort, 81% were men, 56.8% had ulcerative colitis (UC), 36.4% Crohns’ disease (CD) and 6.8% IBD unclassified. Median age at IBD diagnosis was 38 years (IQR 30-47), median age at HIV infection diagnosis was 36 years (IQR 30-42), 46.3% being were firstly diagnosed of IBD. Among UC patients, HIV+ had a lower proportion of extensive disease (24.5% vs 44.8%; P=0.002), and a higher proportion of proctitis (38.8% vs. 16.6%; P=0.002) than controls, without differences on disease proximal progression (7.7% vs 7.9%). Among CD patients, HIV+ presented a higher proportion of colonic involvement than controls (40.6% vs 12,6%, P=0.002) and lower penetrating behavior (10.7% vs 25%; ns). HIV+ had a lower proportion of extraintestinal manifestations (10.7% vs 25.4%; P=0.005). Although it was not statistically significant, a trend towards a lower proportion of hospitalizations (25.6% vs 35.3%) and IBD complications (6.3% vs. 9.2%) in HIV+ was observed. Regarding IBD therapeutic requirements, immunosuppressant (40.5% vs 58.7%; P=0.003) and biological drugs (28.3% vs 42.8%; P=0.020) were used less frequently among HIV+ than among controls. Conversely, HIV+ had a higher rate of OI (38.3% vs 17.8%; P Conclusion The coexistence of IBD and HIV infection seems to be associated with a less aggressive IBD phenotype and a lower use of immunosuppressants and biologicals but with a remarkable rate of OI.

Background Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. Aims Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. Methods IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey‐Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. Results A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4–37.5). Conclusion Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Background Treatment with thiopurines in patients with Inflammatory Bowel Disease (IBD) may be associated with different adverse effects, including acute pancreatitis. Our aims were to evaluate the clinical presentation, severity and management of acute pancreatitis related to thiopurines in patients with IBD. Methods IBD patients with acute pancreatitis secondary to treatment with thiopurines for IBD were identified from the prospectively maintained ENEIDA registry of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU). We included those patients who met the Atlanta diagnostic criteria and had an imaging test that ruled out biliary origin of pancreatitis. Investigators at each participating centre provided additional information on pancreatitis clinical evolution and management. Results We included 290 patients with pancreatitis in 34 centres; 54% were women, 84% had Crohn’s disease and 56% were smokers. Five (1.7%) had had pancreatitis before, but no patient met criteria for chronic pancreatitis. The median age at pancreatitis was 36 years (IQR 27-50). In 94% of cases, pancreatitis occurred after the first thiopurine drug. Azathioprine was the thiopurine used in 97% of cases (median dose 2.3 mg/kg/day (IQR 2-2.5)), and 6% were treated with mercaptopurine (1.5 mg/kg/day (IQR 1-1.5)). Pancreatitis was diagnosed after a median of 23 days (IQR 14-35) since the start of the treatment with thiopurines. 81% required hospitalization for pancreatitis for a median of 5 days (IQR 4-7). Four (1.4%) were severe pancreatitis, 16 (5.5%) moderate, and the rest mild, according to the Atlanta classification. No epidemiological or treatment factors were associated with the severity of pancreatitis. Thiopurine was withdrawn in all patients upon diagnosis of pancreatitis. After 2 months (IQR 1-28) of pancreatitis, 16 patients (5.5%) received thiopurines again (5 the same, 11 a different thiopurine), suffering a new episode of pancreatitis in 12 (75%) after a median of 12 days (IQR 5-34). Pancreatitis occurred in all smokers that were treated again with thiopurines (n=7), compared to 5 of the 9 (56%) non-smokers or former smokers (p=0.04, RR 1.8; 95% CI 1.1-3.2). Conclusion Acute pancreatitis secondary to treatment with thiopurines is mild in most patients, usually appearing during the first month of treatment. The reintroduction of thiopurines, although feasible in some cases, is not recommended due to the high risk of developing a new pancreatitis, especially in smokers.

Background Corticosteroids (Cs) remain the first-line therapy for moderate-to-severe flares in patients with inflammatory bowel disease (IBD), both Crohn’s disease (CD) and ulcerative colitis (UC). On the other hand, their use has been associated to multiple adverse events (AEs) in randomized controlled trials and registries. Nevertheless, recent studies have repeatedly observed that the use of Cs has not decreased in spite of the increasing availability of biological agents and new small molecules licensed for IBD. The impact of Cs therapy on patients’ quality of life (QoL) and the patients’ perception on Cs have not been properly assessed in IBD. The purpose of this study was to assess the impact of a standard Cs course on the patients’ QoL and their satisfaction with treatment. Methods A prospective, longitudinal and observational study was conducted in adult IBD. All subjects received the same standard Cs regimen: starting dose of 1mg/kg/day (maximum 60mg/day) and tapering after 14 days with 10mg per week until reach 20mg/day, thereafter reduction was 5mg per week. QoL was assessed by the IBDQ-9 questionnaire at baseline, week 4 and at the end of Cs. Treatment satisfaction was assessed by the TSQM1.4 questionnaire at week 4 and at the end of Cs. Results Sixty-three patients were included in the study (54% CD and 43% UC; mean age 38.5±14.9 years; 46%females). Cs therapy failed in 41% of cases (active disease upon Cs discontinuation or need for rescue therapy). AEs attributable to Cs were reported in 84.1%, the most frequent were dermatologic (acne and moon face) (60.3%), hypokalemia (44.8%) and poor quality of sleep (40%). Serious AEs were reported in 20,6%, mostly mild or moderate infections that resolved without sequelae. IBDQ-9 scores increased 12.4 and 13.5 points at 4 weeks and at the end of Cs, respectively (p Conclusion A standard Cs course significantly increases the QoL of patients with IBD. Furthermore, a high satisfaction with treatment was perceived by patients.

Background Our aim was to evaluate the effectiveness and safety of tofacitinib in ulcerative colitis (UC) in real life. Methods Patients from the prospectively maintained ENEIDA registry treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 4, 8 and 16. The last-observation-carried-forward method was used in patients that stopped tofacitinib before the time-points for clinical assessment. Variables associated with short-term remission at week 8 were identified by logistic regression analysis. The cumulative retention rate and the cumulative incidence of relapse over time were assessed by survival curves. Cox-regression analysis was performed to identify predictive factors of tofacitinib discontinuation or relapse over time. Data quality was assessed by remote monitoring. Results 113 patients were included (Table 1 and Figure 1) and exposed to tofacitinib a median of 44 (interquartile range = 30–66) weeks. Response and remission at week 8 were 60% and 31%, respectively (Figure 2). In multivariate analysis, higher PMS at week 4 [odds ratio (OR)=0.2; 95% confidence interval (CI) = 0.1–0.4] was the only variable associated with the likeliness of achieving remission at week 8. Higher PMS at week 4 (OR = 0.5; 95% CI = 0.3–0.7) and higher PMS at week 8 (OR = 0.2; 95% CI = 0.1–0.5) were associated with lower probability of achieving remission at week 16. Twenty per cent of those without remission at week 4, and 12% of those without remission at week 8, achieved remission at week 16. A total of 45 patients (40%) discontinued tofacitinib over time (Figure 3); the discontinuation rate was 34% and 46% at 24 and 52 weeks, respectively. PMS at week 8 was the only factor associated with tofacitinib discontinuation [Hazard ratio (HR) = 1.5; 95% CI = 1.3–1.6)]. A total of 33 patients had remission at week 8; from them, 65% relapsed 52 weeks after achieving remission; 9 patients increased the dose to 10 mg /12 h and 5 reached remission again. No factors associated with relapse over time were identified. Eighteen patients had adverse events (4 hypercholesterolaemia, 2 herpes zoster, 3 infections, 2 dyspnoea, 1 neoplasia, 1 lymphopenia, 1 headache, 1 hypertriglyceridaemia and 4 others). No thromboembolic events were reported. Conclusion Tofacitinib is relatively effective in UC patients in real practice even in a highly refractory cohort. Only 10% of the patients without remission at week 8 reached remission at week 16. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure. Over 60% of patients that achieve remission, relapse over time. Safety was consistent with the known profile of tofacitinib

Background Spanish inflammatory bowel disease (IBD) group (GETECCU) mission is to promote healthcare, teaching and research of excellence. Our vision is to establish standards of quality of care and generate a mark of excellence and reliability for IBD patients and the different agents involved in all its processes. The aim of this study was evaluate the impact of a program for certification of IBD units (CUE program). Methods Identification of quality indicator for certification of IBD Units was based on CUE Delphy methodology that finally selected 53 quality indicators (12 structure, 37 process and 4 results), which were subjected to a normalisation process (Calvet X et al. JCC 2014; 8: 240–51). This process consisted of face-to-face protocoled meetings with a committee of experts that proceeded to defined/justified the use of each indicator considering objectiveness and the measure of compliance. Applications for certification in the program are made voluntarily through the GETECCU secretariat. From GETECCU, the candidate units are counselled through a consulting round before an audit drill and finally, the formal audit carried out by an independent certifying agency. This audit consists of the review of all selected indicators and includes a review of 40 random medical records. If 80–90% compliance is achieved, the qualification of ‘advanced’ is obtained and the unit is re-certified in 2 years. If it exceeds 90%, the rating is ‘excellence’ and the unit has to be re-certified in 3 years. An anonymous survey was conducted among certified units to assess satisfaction with the program Results The CUE program started in 2017. As of November 2019, there are 53 IBD units adhered to the certification nationwide program, of which 42 have already been audited and 40 certified. Twenty-three units achieved the qualification of excellence (56%), 17 achieved an advanced qualification and 5% had not passed the certification. The remaining 11 are currently in the process of being audited. After an IBD Unit achieve the certification an act of official delivery is carried out with the presence of patient associations, public care authorities and the board of GETECCU. Results are published in the State Official Gazette. Survey main results were the average perceived improvement, averaged as 8.5, out of 10. The most important aspect of improvement is data recording followed by health and patient satisfaction results Conclusion The establishment of quality standards certification programmes in multidisciplinary units improves the quality of care offered to IBD patients. The acceptance among the health community for adherence to these projects is very high despite being voluntary. The support of patient associations and managers is essential to value these types of projects

Background There are limited data of long-term ustekinumab administered according to the doses recommended in the UNITI studies. The objective of this study was to assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn’s disease (CD) (LONG-CROHNUSK Study). Methods Multicentre study of CD patients starting ustekinumab at the recommended dose based on weight ~6 mg/kg IV week 0, 90 mg SC week 8 and maintenance 90 mg SC every 8 or 12 weeks and with 1 year of follow-up. Values for 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), surgeries and hospitalisations were documented. Potential predictors of clinical and endoscopic remission were examined. Results Four hundred and seven patients were analysed (Table 1). For the maintenance dose, ustekinumab 90 mg was administered SC every 12, 8 and 4 weeks in 56 (14%), 318 (84.5%) and 7 (1.5%) patients, respectively. An interval reduction was applied for 118 patients (29%). Before 52 weeks, treatment discontinuation occurred in 71 patients (17%). 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 ( Conclusion This is the first study to show the real-world long-term effectiveness, endoscopic improvement and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

Background The prevalence of hepatitis C virus infection (HCV) in patients with inflammatory bowel disease (IBD) ranges from 1–6%. Direct-acting antivirals (DAAs), with cure rates >90%, represent a radical change from interferon-based therapies. The ECCO guidelines (Kucharzik JCC 2021) warns about the risk of IBD reactivation due to the effect of DAAs, but HCV management in this situation is uncertain given the lack of evidence. AIMS: To evaluate: 1) Effectiveness and safety of DAAs in IBD; 2) Interaction of DAAs with IBD drugs, particularly immunosuppressants and/or biologics. Methods Multicenter retrospective study of patients with IBD and HCV treated with DAAs identified on the ENEIDA registry (January 2011-February 2021). Variables evaluated: age, gender, location, extent, phenotype and activity of IBD, treatments, anti-HCV and viral load, DAA treatment and duration, fibrosis and hepatic decompensations, adverse effects (AE) and interactions. Results We included 79 patients with IBD and HCV treated with DAAs (47 sofosbuvir, 28 ledipasvir, 7 daclatasvir, 8 velpatasvir, 1 simeprevir, 16 paritaprevir+ritonavir+ombitasvir, 14 dasabuvir, 3 grazoprevir+elbasvir, 13 glecaprevir+pibrentasvir). Clinical and demographic characteristics: mean age (years) 54+/-12.66SD; 62% male, 77.2% genotype 1, 32.6% advanced fibrosis (none Child B-C). A 78.5% (n=62) received IBD treatment (39 salicylates, 20 azathioprine, 1 methotrexate, 4 corticosteroids, 10 antiTNF, 2 vedolizumab, 2 ustekinumab, 1 apheresis). A 17.7% (n=14) had active IBD (64.3% remained unchanged, 21.4% improved and 14.3% worsened) and 82.3% (n=65) were inactive at the onset of ADD. Of these, 9.2% (n=6) developed mild-moderate activity (4 mild and 2 moderate). In 85% (n=67) no treatment changes were made, in 9% (n=7) it was intensified and in 6% (n=5) it was de-intensified. Adherence to DAAs and sustained virologic response was obtained in 96.2% (n=76). A total of 7 (8.9%) AE were notified, of which 5 were possibly/probably related to DAAs (100% mild) and 2 were unrelated (1 azathioprine withdrawal due to pancytopenia). The AE were unrelated with the presence of inflammatory activity, type of IBD, liver fibrosis, use of immunosuppressants, biologics, or with any DAA regimen. Conclusion This is the first reported series of IBD patients infected with HCV and treated with DAAs, we showed that DAA are effective and safe. They do not trigger IBD flare-ups, nor have more AE than in patients without IBD. Moreover, they do not have clinically significant pharmacological interactions with immunosuppressants and/or biologics. Thus, the eradication of HCV with DAA in IBD patients must be the same of the HCV infected patients without IBD, based on EASL recommendations.

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 Previous studies comparing inflammatory bowel disease(IBD) features between migrant and native patients have shown clinical phenotype differences. To date, no study has focused on IBD immigrants(MP) in Spain. The aim of this study was to explore the features of MP in Spain and to compare age of disease onset, IBD phenotype and therapeutic requirements with native-born IBD patients(NP). Methods This was an observational, multicentric and case-control study of the nationwide ENEIDA registry. We selected all IBD patients who were born outside of Spain and compared with a control cohort of NP. All included patients were diagnosed with IBD before 2015. Results A total of 13,524 patients were included(1864 MP and 11660 NP).The most prevalent ethnic migrant group was Caucasian(771, 41%), followed by Latin American(572, 31%) and Arabian(341,18%), whereas Asian represented only 6%. Table 1 summarizes the demographic and phenotypic features. 71% of MP were diagnosed with IBD in Spain. There was not a gender predisposition to IBD in the overall migrant group, however more female UC MP were detected compared to UC NP(52 % vs 45%, p Conclusion In the largest cohort of migrant IBD patients in Spain, immigrants were younger, had a shorter disease duration and required a higher use of biologics than natives, pointing phenotypic differences in this population and a universal access to the healthcare system all over the country.

Background Older age has been confirmed as a risk factor for severe clinical presentation of SARS-CoV-2 disease (COVID-19). The prevalence of confirmed SARS-CoV-2 infection in Catalonia among people over 60 years is 6.6%. Biological agents have not been associated with a higher incidence nor a worse prognosis of COVID-19. However, the role of immunosuppressants (IMS) on this issue is still to be elucidated. Moreover, there are scarce data related about COVID-19 in inflammatory bowel disease (IBD) patients under IMS, and none focusing in elderly IBD. Our aim was to describe and to compare the incidence and severity of COVID-19 in patients over 65 years of age with IBD, particularly in relation to the use of IMS. Methods We performed a retrospective cohort study including IBD patients over 65 years since January 2020, from two referral centres in the Barcelona metropolitan area (Catalonia, Spain). Patients were grouped in two cohorts regarding the use or not of IMS (thiopurines or methotrexate). Patients on biological treatment were excluded. We identified those cases with confirmed infection with SARS-CoV-2 (positive PCR) during the period from 1st of March 2020 (the beginning of the pandemic in Catalonia) to 1st March 2021 (the beginning of vaccination in the elderly). Demographic data, IBD comorbidities, concomitant non-IBD related treatments, and SARS-CoV-2 infection outcomes were recorded. Results Four-hundred and eighteen elderly IBD patients were included. The median age was 74 years (IQR 69–78), 52% were male; 70% had ulcerative colitis, 28% Crohn’s disease and 2% IBD unclassified, 62% had arterial hypertension, 22% diabetes mellitus, 22% cardiovascular disease, 15% chronic obstructive pulmonary disease, 10% chronic renal disease, 5% were active smokers. There were no differences regarding comorbidities and non-IBD treatments between the two study groups. From the whole cohort, 89 (21.3%) patients were on IMS (86 with thiopurines, 3 with methotrexate). The median time on IMS was 121 months (IQR 60–162). During the study period, 32 patients (7.7%) had confirmed SARS-CoV-2 infection (7 of whom were on IST; 7.6% not on IMS vs. 7.9% on IMS, P=0.933). Seventeen (53%) patients required hospital admittance (4% not IMS vs. 4.5% on IMS; P=0.818); 4 of them developed COVID-19 related complications (3 patients not on IMS vs. 1 on IMS), and 7 (22%) patients died (6 not on IMS vs. 1 patient on IMS). Conclusion The rate of SARS-CoV-2 infection among elderly IBD patients is quite similar to that reported in the elderly background population. In elderly IBD patients, SARS-CoV-2 infection was associated with a high admission rate and mortality, regardless of the use of IMS.

Background The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice. Aims Primary: to evaluate the durability of ustekinumab treatment in UC patients in clinical practice. Secondary: to assess the short-term response (at week 16) and the long-term effectiveness (at maximum follow-up) and to assess the safety of ustekinumab in clinical practice. Methods Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Results 95 patients were included (table 1). At week 16, 53% of patients had clinical response (including 35% of patients in remission) (figure 1). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with clinical remission. Long-term remission is represented in figure 2. 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72 (figure 3); primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusion Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

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 Crohn’s disease (CD) is a chronic inflammatory bowel disease that normally requires bowel surgical resection due to intra-abdominal inflammatory complications such as fistulae and stenosis. However, 90% of patients that underwent surgery and did not receive prophylaxis, suffer from postsurgical endoscopic recurrence within one year. Methods The objective of this study is to understand the de novo postsurgical lesion formation in order to stablish a potential mechanism of action and its derived predictive signals to devise preventive strategies. To achieve it, transcriptome analyses of the inflamed and macroscopically unaffected zone of the ileocecal resection from 20 patients from a hospital cohort and 10 controls were performed. Patients were classified for early postsurgical recurrence by means of Rutgeerts index (i0 Results The transcriptome results showed there were no differences neither between i0, i1 and i2a (anastomotic lesions) nor when comparing i2b (non-anastomotic lesions) vs ≥i3. However, when comparing i0+i1+i2a vs. i2b+i3+i4 there were differently expressed genes highlighting ADIPOQ in the inflamed zone and the FXR/FGF19 axis in the unaffected zone. When replicating the results in the corroborative cohort, we identified FXR and other xenobiotic nuclear receptors as the genes differentially expressed in i2a vs i2b, i3 and/or i4, mainly in the macroscopically unaffected zone. Specifically, the differentially expressed genes were: MOGAT2, PXR, FXR and AHR (i2a vs i4), PPARα and FXR (i2a vs i3), TMIGD1, PPARα, FXR and AHR (i2a vs i3+i4) and FXR (i2a vs i2b+i3+i4). Conclusion Nuclear receptor FXR is activated in the ileum by bile acids action and it is key in the lipid metabolism regulation and in the bile acids production by means of FGF19. Moreover, ileal FXR, as well as other xenobiotic nuclear receptors, actively participates in the enhancement of the intestinal barrier function and in the innate immunity regulation. In conclusion, the results obtained in this study suggest a link between bowel xenobiotic metabolism and the de novo lesion formation in previously unaffected areas in the postsurgical recurrence in CD.

Background The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. With these premises, the aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic; the outcomes among those under immunosuppressants/biologics for IBD; the risk factors for contracting the infection and poor outcomes; and the impact of the infection after three-month follow-up. Methods Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results A total of 484 patients with COVID-19 from 63 centres were included: 247 Crohn’s disease, 223 ulcerative colitis and 14 unclassified colitis; median age 52 years (IQR: 42–61), 48% women and 44% ≥1 comorbidity. Diagnosis was made by PCR: 63% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 16 patients died from COVID-19 (mortality:3.3%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Male gender (OR 1.56; 95%CI:1–2.4, p=0.05), ≥40 years of age (OR 2.55; 95% CI:1.4–4.8; p=0.004), Charlson score ≥1 (OR 2.1; 95% CI:1.3–3.5; p=0.004), and systemic steroids Conclusion IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients. The use of aminosalicylates and the risk of a worse outcome deserves a deeper analysis. Funded by the Carlos III Health Institute (COV20 / 00227).

Background Some genetic polymorphisms (present in less than 30% of patients) and environmental factors, such as tobacco exposure, have been identified to increase the susceptibility for developing inflammatory bowel disease (IBD), but it is suspected that there may be other still unknown environmental or epidemiological factors. In this sense, some studies suggested an increased incidence of IBD in individuals undergoing bariatric surgery (BS) for morbid obesity (MO). We aimed to assess whether BS or MO are associated with an increased risk of developing IBD. Methods All individuals resident in Catalonia (7.7 million inhabitants in 2021) with a diagnosis of obesity or MO within the period 2005–2020 were identified from the Catalan Public Health System Database. Children under the age of 18 and those diagnosed with IBD prior to the diagnosis of obesity or MO were excluded. Individuals BS and those with a new diagnosis of IBD were identified, and the likelihood of developing IBD was analyzed by Kaplan-Meier survival analysis. A Cox regression multivariable analysis was performed to assess independent risk factors for the development of IBD, Crohn’s disease (CD) and ulcerative colitis (UC). Results Three cohorts were identified: 94,473 individuals with MO; 1,009,256 with obesity; and 14,698 who underwent BS during the study period. A total of 4,277 new diagnoses of IBD were identified, of which 78 among individuals who underwent BS prior to IBD diagnosis (0.84 cases per 1000 person-years), 409 among individuals with OM but without BS (0.90 cases per 1000 person-years), and 3,790 in obese individuals (0.60 cases per 1000 person-years). The likelihood of developing IBD was significantly higher in patients with MO as compared with obese patients (HR 1.46; 95%CI 1.32–1.62). These differences were maintained when the likelihood of developing CD or UC were assessed separately. In the multivariable logistic regression analysis, MO (HR 1,68; CI95% 1.41–1.99), female gender (HR 1.17; 95%CI 1.05–1.31) and active smoking (HR 1.62; 95%CI 1.43–1.84) were associated with an increased risk of CD. In UC, MO (HR 1,36; 95%CI 1.19–1.55) and BS (HR 2.62; 95%CI 1.34–2.11) were independent risk factors, whereas female gender (HR 0.86; 95%CI 0.79–0.93) was an independent protective factor. Conclusion MO is an independent risk factor for the development of IBD, for both CD and UC, whereas BS seems to increase the risk only for UC.

Background Oral corticosteroids remain the treatment of choice for moderately active flares of ulcerative colitis (UC). In early controlled studies, oral corticosteroids achieved clinical remission rates of, 30–60% at, 30 days. Some small prospective studies observed that the administration of high-dose intravenous bolus of methyl-prednisolone accelerated their therapeutic action and increased the rate of clinical response. We aimed to evaluate if the outpatient administration of intravenous, high-dose, methyl-prednisolone bolus increases the efficacy of a conventional course of oral prednisone in moderately active UC. Methods Prospective, multicentre, controlled, randomized, open-label study comparing the therapeutic efficacy of a standard oral prednisone schedule with the same schedule preceded by a three-day regimen of high-dose intravenous bolus of methyl-prednisolone. Inclusion criteria were: Moderately active, left-sided/extensive UC (total Mayo score, 6–10), with no prior exposure to immunosuppressants or biologics, and no corticosteroid treatment in the last, 6 months. Patients were randomized to oral prednisone, 60mg/day (ORAL group) or the same schedule preceded by intravenous bolus of, 500mg of methyl-prednisolone for three consecutive days (BOLUS group), stratified by the baseline use of oral, 5ASA and UC onset. Early clinical response was defined as the reduction of the baseline partial Mayo Score (pMS) by at least three points with at least a decrease by, 1 point in rectal bleeding and with an absolute value of, 0 or, 1, seven days after starting treatment (EUDRA CT:, 2016-001170-15)(Clinicaltrials.gov: NCT02921555) Results In all, 71 patients (38 ORAL, 33 BOLUS) were included. At baseline, the median pMS was, 6 (IQR, 5–7). In, 21% of the patients, the index flare was the onset of UC and, 68% had never received systemic corticosteroids for UC. There were no differences in baseline clinical and demographic features between the two study groups. At day, 7, the proportion of patients fulfilling early clinical response criteria was similar in both groups (BOLUS, 63% vs. ORAL, 58%; p = 0.6), but a significantly greater reduction in pMS at day, 3 (-3.4. vs -1.7; p Conclusion The addition of three high-dose intravenous bolus of methyl-prednisolone to a standard schedule of oral corticosteroids achieves a faster and more intense response in the short-term in moderately active flares of UC, but it does not increase the clinical response rate at seven days. The impact of these effects on the medium-term outcomes is still to be assessed.

Background: Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD). Aim: To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD. Methods: Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset). Results: One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). Conclusions: Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC.

Background Methotrexate (MTX) is currently used in steroid-dependent patients with moderate-to-severe Crohn’s disease (CD) when thiopurines have failed or are contraindicated. Although its efficacy has been proved for both induction and maintenance of remission, its use is limited due to the rate of associated adverse events. Polymorphisms in the folate pathway might predict the efficacy and toxicity of MTX. Our aims were to evaluate the predictive value of these polymorphisms of MTX efficacy and safety in CD. Methods Patients from ENEIDA registry of GETECCU who were treated with MTX on monotherapy and of whom genomic DNA was available, were identified. Clinical efficacy and MTX-related toxicity were collected, and 10 variants from ATIC, DHFR, MTHFR, RFC1, ABCB1 and ABCC3 genes were genotyped with TaqMan assays. Results One hundred and twenty nine patients were included, 55% were female and 31% active smokers. MTX was used as first and second-line therapy in 10% and 60% of patients, respectively, at a mean dose of 22 mg and for a median time of 14 months. Thirty-seven per cent of patients achieved clinical remission, whereas 34% were non-responders (MTX failure). Forty patients (30%) developed MTX-related toxicity, with nausea and vomiting, myelotoxicity and hepatotoxicity as the most frequent adverse events (37%, 15% and 15%, respectively). MTX was discontineud in 19% of the patients due to toxicity. In the multivariable analysis, patients with the AA genotype for the rs408626 DHFR variant was predictive of a higher efficacy as compared to the G allele carriers (RR 0.372, p=0.026), and smoking was associated with a higher risk of MTX therapy failure (RR 2.676, p=0.015). Moreover, the CC genotype for the rs1476413 MTHFR variant and the TT genotype for the rs4793665 ABCC3 variant were independently associated with a higher risk of MTX toxicity (RR 2.357, p=0.038 and RR 2.368, p=0.044, respectively). Conclusion Genetic polymorphisms related to the folate pathway (mainly the variant rs408626 of DHFR, rs1476413 of MTHFR and rs4793665 of ABCC3) seem to impact on MTX efficacy and toxicity in CD. Smoking could also influence MTX efficacy.

Resumen Las manifestaciones extraintestinales en general y, de entre ellas, las articulares en particular, suponen un problema frecuente en los pacientes con enfermedad inflamatoria intestinal. De hecho, la relacion entre ambas entidades parece estrecha y cada vez hay mas datos que indican que el intestino desempena un importante papel en la patogenia de las espondiloartritis. La asociacion de la enfermedad inflamatoria intestinal con algun tipo de espondiloartritis supone un escenario clinico complejo. Se hace necesario, por tanto, que gastroenterologos y reumatologos puedan trabajar juntos y establecer una comunicacion fluida que permita a cada paciente recibir el tratamiento mas adecuado para cada situacion concreta. El objetivo de esta revision es el de establecer unas recomendaciones sobre el tratamiento de los pacientes con enfermedad inflamatoria intestinal y espondiloartritis asociada, en cada uno de los distintos escenarios clinicos.

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.

Background Ustekinumab has shown promising results in ulcerative colitis (UC) in the development program (UNIFI) that should be confirmed in clinical practice. Our aim was to evaluate the effectiveness and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry that received at least 1 dose of ustekinumab intravenously due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 8 and 16. The last-observation-carried-forward method was used in patients that stopped ustekinumab treatment before week 8 or 16. Variables associated with short-term remission were identified by logistic regression analysis. Data quality was assessed by remote monitoring. Results Forty-seven patients were included (Table 1); all of them had been previously exposed to biologic agents (70% to >2): 100% to anti-TNF and 83% to vedolizumab. A total of 26% had been exposed to tofacitinib. Seventeen patients (36%) had response at week 8 [3 of them (6%) had remission]; 16 patients (34%) had response at week 16 [5 of them (11%) had remission] (Figure 1). There was a statistically significant decrease in C-reactive protein (CRP) concentration during the induction only in patients with a response at week 16 (Figure 2). The proportion of patients with CRP elevated at baseline and at week 8 was higher among non-responders at week 16 (Table 2). In the multivariate analysis, higher PMS at week 8 [odds ratio (OR) = 0.5; 95% confidence interval (CI) = 0.3–0.9)] and CRP over the upper normal limit at week 8 (OR = 0.1; 95% CI = 0.01–0.8) were associated with lower probability of response at week 16; steroids during induction increased the probability of response at week 16 (OR = 8; 95% CI = 1–71). Of patients without response at week 8, only 7% achieved response at week 16. Seventeen out of 31 patients continued ustekinumab beyond week 16, despite being non-responders. Of these 17 patients, 4 reached remission after the third dose, 1 after the fifth and 1 after the seventh one. There were 2 infections, one of them with fatal consequences (in a patient under steroids and tacrolimus due to renal transplant). Conclusion Ustekinumab shows benefit in some UC patients in real practice, even in a very refractory cohort in which the drug was prescribed as last resort. Patient status at week 8 seems to be a good predictor of response after the induction. Safety was consistent with the known profile of ustekinumab.

Background INFEII registry (ClinicalTrials.gov: NCT02904590) is a prospective study promoted by GETECCU to determine the incidence and risk factors of infection in an inception cohort of IBD patients. Despite preventive measures and recommendations of scientific societies, TB remains a problem in patients with IBD treated with immunosuppressants (IMM) and biologics. AIMS To asses: (1) the screening of TB performed at the time of inclusion of a patient in the INFEII registry, (2) the incidence of latent TB; and (3) compliance with national and European recommendations. Methods A longitudinal prospective study of incident cases with IBD, initiated in October 2016 and with a planned follow-up of 5 years. In September 2019, INFEII registry had 1241 patients from 28 centres throughout Spain. The study protocol determines the mandatory fulfilment of TB screening in every patient, leaving to the centre the freedom of decision on what procedures to perform. Guidelines recommend a mandatory study before starting immunosuppression, especially with biological treatment, using the combination of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) or at least one TST with a booster test1,2. Results Of the 1241 patients 233 (19%) had no screening, 494 (40%) had one [TST 158, IGRA 299, thorax-X-ray 37], 288 (23%) two [TST + IGRA 87, IGRA + thorax-X-ray 130, TST + thorax-X-ray 30, TST + booster 41], 128 (10%) three [TST + IGRA + thorax-X-ray 65, TST + booster + IGRA 23, TST + booster + thorax-X-ray 40] and 98 (7.9%) the four tests [TST + booster + IGRA + thorax-X-ray]. 486 patients (48%) receive pharmacological immunosuppression (172 IMMS, 195 biologics, 119 COMBO) and from them 198 (41%) followed the guidelines recommendation (131 TST and IGRA and 118 TST-booster), 245 (50%) had some method for TB screening [TST 43, IGRA 112, thorax-X-ray 15, IGRA + thorax-X-ray 57, TST + thorax-X-ray 18] and 43 patients (8.8%) had no screening. With the baseline screening, latent TB was detected in 134 patients (13%), 63 (47%) receiving anti-TB chemotherapy. In patients initiating immunosuppression, latent TB was detected in 35 cases [of which 28 received prophylaxis but 7 under IMM did not]. Active TB was detected in 4 cases: 2 during baseline screening, one without screening and one with negative screening (negative TST and IGRA, without booster receiving biological treatment). Conclusion Despite TB in IBD is a relevant problem, there is ample room for improvement for the implementation of mandatory minimum screening recommendations, even in prospective protocolised projects. References

Background Thiopurine (TP) withdrawal in patients with Crohn’s disease (CD) in clinical remission (CR) is controversial. Our aim was to describe the evolution of CD patients in CR who discontinued TP prescribed to maintain a remission previously achieved with medical treatment, and to detect predictors of reactivation after withdrawal. Methods Multicentric observational retrospective study including CD patients in RC under TP treatment, who electively discontinued TP. Relapse was defined as the need to start any specific treatment for CD, including surgery. Informed consent was obtained from the inclusion in the Eneida database. Results We included 78 patients (52.6% females, age 45(19–77) years) of whom 57 presented an inflammatory, 12 a stricturing and 9 a penetrating behaviour; 31 patients had terminal ileum involvement, 9 colonic, 36 ilecolonic, and 2 ileocolonic plus upper gastrointestinal involvement, whilst 17 also had perianal disease. Mean disease duration was 13.47 (3.02–35.02) years. 48.7% had never smoked whilst 24.4% were active smokers. TP was started to maintain remission previously achieved with medical therapies in 78 patients (100%). Median azathioprine dose was 2.11 (1.3–2.6) mg/kg/d, and of 6-mercaptopurine (6MP) 1.44 (1–2) mg/kg/day. The median duration of TP treatment was 52.79 (3–268) months and of steroid-free remission 49.41 (1–177) months. Reasons for TP withdrawal were: patient choice/request in 20 (25.6%), physician proposal in 28 (25.7%), drug-related adverse events in 19 (24.4%) and miscellaneous in 11 (14.1%). By the time of TP discontinuation, median CRP was 5.08 mg/l (0.1–157.9), fecal calprotectin(FC) 282.38 µg/g (2.4-4430) and a mean 0.45 (0–4) in Harvey–Bradshaw Index (HBI); those who relapsed presented median CRP of 15.31 mg/l (0.1–125.31), fecal calprotectin (FC) 462.22 µg/g (90–1240) and a mean 5.46 (0–15) in HBI. These differences were statistically significant. During a 5.08 (0.12–13.05) years follow-up, 38 (48.1%) patients relapsed, with treatment duration being the only factor associated to risk of relapse (Or = 0.659 IC95 0.43–0.98, p = 0.04) in the multivariant analysis (IMAGE1). Conclusion Thiopurine withdrawal in the context of sustained remission in CD is associated with relapse in almost half of the patients after a median follow-up of 5 years. Thiopurine treatment duration of shorter than 5 years was shown to carry greater risk for relapse.

Background Three anti-TNFs (one intravenous and two subcutaneous) are licensed for the treatment of ulcerative colitis (UC). However, it is not known if the efficacy of a second anti-TNF changes on whether it is intravenous or subcutaneous; this could justify the indication of biological agents with a different mechanism of action in second line. The aim of this study was to compare the efficacy of a second subcutaneous or intravenous anti-TNF in UC. Methods Patients from the prospectively maintained ENEIDA registry treated with consecutively intravenous and subcutaneous anti-TNF, who were naïve to biological agents, were identified. Patients were classified according to the administration route of the first anti-TNF in: IVi (intravenous initially) or SCi (subcutaneous initially). Patients treated for extraintestinal manifestations or pouchitis were excluded. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS) at baseline, 14 and 52 weeks. Loss of response, dose-escalation and treatment discontinuation were also assessed. Results 372 UC patients were included (270 IVi and 102 SCi). Both cohorts were similar in clinical-epidemiological characteristics, except for a higher proportion of patients with moderate-to-severe clinical activity at the beginning of the first anti-TNF in the IVi group (82% vs. 71%; p = 0.017) and at the beginning of the second anti-TNF (62% vs. 74%; p = 0.04). Clinical response and remission rates at week 14 for the second anti-TNF were 41% and 29% in IVi vs. 47% and 25% in SCi, respectively (p = ns). At week 52, clinical response/remission rates of the second anti-TNF were 37%/32% in IVi vs. 40%/29% in SCi (p = ns). A higher response rate at 14 weeks with the second anti-TNF was detected in the SCi group (40% vs. 68%; p = 0.012) when the reason for withdrawal of the first anti-TNF was secondary loss of response. The cumulative persistence of the second anti-TNF treatment in IVi and SCi were 55% and 54% after 1 year, and 41% and 40% after 2 years, respectively (p = ns). The SCi group had lower rates of dose-escalation with the second anti-TNF than IVi (34% and 29% in SCi vs. 57% and 49% in EVi, at 12 and 24 months, respectively -p = 0.004-). Dose-escalation of the first anti-TNF and moderate-to-severe clinical activity at the beginning of the second anti-TNF were associated with a lower probability of remission with the second anti-TNF in the short- and long-term. Conclusion The efficacy of infliximab after failure/intolerance of a subcutaneous anti-TNF is similar to that of subcutaneous anti-TNFs after infliximab failure/intolerance.

Background Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases, these drugs are contraindicated or have previously failed. Vedolizumab was licensed for CD some years ago but scarce data on its efficacy for the prevention of POR is available. Methods All CD patients in whom vedolizumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD, GETECCU). We evaluated the rates of Endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score >i1 and advanced endoscopic POR by >i2. Results Twenty-three patients were included; vedolizumab was started after a median time of 23 days (IIQ21-73). Concomitant immunosuppressants were used in 17%; 18% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 13% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. Thirty-four per cent had been exposed to vedolizumab prior to the index surgery (26% within the last 6 months). The median time of follow-up on ustekinumab was 26 months (IQR 11–31). Eighty-three per cent of patients had at least one endoscopic assessment within 18 months after surgery: 40 % had endoscopic POR and 15% advanced endoscopic POR. Additionally, 22% presented clinical POR at the discretion of the treating physician and 9% developed surgical POR. Conclusion In a small clinical practice cohort, vedolizumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR.

Immunosuppressant therapies (IMTs; thiopurines, anti-tumor necrosis factor agents) may influence the immunologic control of cancer and might facilitate the spread and recurrence of cancer. This study assesses the impact of the use of IMTs on the development of incident cancers (recurrent or new) in patients with inflammatory bowel disease (IBD) and a history of malignancy.Patients with IBD included in the ENEIDA registry with a history of cancer without being exposed to IMTs were identified and retrospectively reviewed and compared regarding further treatment with IMTs or not by means of a log-rank test.Overall, 520 patients with previous extracolonic cancer naive to IMTs before the diagnosis of cancer were identified. Of these, 146 were subsequently treated with IMTs (exposed), whereas 374 were not (nonexposed). The proportion of patients with incident cancers was similar in both exposed (16%) and nonexposed (18%) patients (P = 0.53); however, there was more than a 10-year difference in the age at index cancer between these 2 groups. Cancer-free survival was 99%, 98%, and 97% at 1, 2, and 5 years in exposed patients, and 97%, 96%, and 92% at 1, 2, and 5 years in non-exposed patients, respectively (P = 0.03). No differences in incident cancer rates were observed between exposed and nonexposed patients when including only those who were exposed within the first 5 years after cancer diagnosis.In patients with IBD and a history of cancer not related to immunosuppression, the use of IMTs is not associated with an increased risk of new or recurrent cancers even when IMTs are started early after cancer diagnosis.

Background and Aims Steroid-refractoriness is a common and unpredictable phenomenon in ulcerative colitis [UC], but there are no conclusive studies on the molecular functions involved. We aimed to assess the mechanism of action related to steroid failure by integrating transcriptomic data from UC patients, and updated molecular data on UC and glucocorticoids. Methods MicroRNA [miRNA] and mRNA expression were evaluated by sequencing and microarrays, respectively, from rectal biopsies of patients with moderately-to-severe active UC, obtained before and on the third day of steroid treatment. The differential results were integrated into the mathematical models generated by a systems biology approach. Results This computational approach identified 18 proteins that stand out either by being associated with the mechanism of action or by providing a means to classify the patients according to steroid response. Their biological functions have been linked to inflammation, glucocorticoid-induced transcription and angiogenesis. All the selected proteins except ANP32E [a chaperone which has been linked to the exchange of H2A.z histone and promotes glucocorticoid receptor-induced transcription] had previously been related to UC and/or glucocorticoid-induced biological actions. Western blot and immunofluorescence assays confirmed the implication of this chaperone in steroid failure in patients with active UC. Conclusions A systems biology approach allowed us to identify a comprehensive mechanism of action of steroid-refractoriness, highlighting the key role of steroid-induced transcription and the potential implication of ANP32E in this phenomenon.

Background : In patients with Crohn's disease (CD), endoscopic recurrence precedes clinical recurrence after ileocolonic resection. Guidelines recommend ileocolonoscopy within the first year after surgery. The study examined endoscopic monitoring and treatment decisions in CD patients in a real-world setting. Methods : The Practicrohn study involved adult patients from 26 Spanish hospitals who underwent ileocolonic resection with anastomosis from 2007 to 2010. Medical records data were collected retrospectively from diagnosis to index surgery and up to 5 years after surgery. Results : Of 314 analyzed patients, 262 (83%) underwent endoscopic evaluation, but only 30% (n = 95) had planned endoscopy as part of follow-up within the first year after surgery. An upward trend was observed in the proportion of endoscopies performed or planned within the first year after surgery across the selection period. More patients with than without endoscopic recurrence in the first year after surgery had a medication change, mainly for endoscopic activity in the absence of clinical symptoms (54 vs 13%; p = 0.02). Conclusions : Between 2007 and 2010, endoscopic monitoring of patients within the first year after CD-related surgery was less than adequate based on current standards, but showed improvement. Medication changes were in general agreement with current guideline recommendations. This work was presented as a poster (number P686) by M. Barreiro-de Acosta et al. at ECCO (European Crohn's and Colitis Organisation) '18 in Vienna, Austria, 14-17 February 2018.

Background: In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA). Aims: To evaluate health-related quality of life (HRQoL) in APPRECIA trial. Methods: HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52. Results: Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p < 0.001 and p = 0.006 for all comparisons, respectively). There were no differences between treatment arms in mean change in SIBDQ-9 and EQ-5D at weeks 24 and 52 vs baseline. Only patients without endoscopic recurrence had significant improvement in SIBDQ-9 (p < 0.001) and EQ-5D (p < 0.001) at week 52. At week 52, there was a high to moderate negative correlation between CDAI score with SIBDQ-9 score( Pearson's r: -0.768) and with EQ-5D index (r: -0.644). Conclusion: HRQoL improved after intestinal resection in CD, irrespective of the postoperative therapyused (ADA or AZA). Outcomes in HRQoL were associated with prevention of endoscopic recurrence, sinceimprovements in HRQoL were only significant in patients with endoscopic remission at 1 year. (c) 2019 Editrice Gastroenterologica Italiana S. r. l. Published by Elsevier Ltd. All rights reserved.

Resumen Introduccion La proctitis ulcerosa (PU) constituye un cuarto de los casos de colitis ulcerosa (CU), con caracteristicas clinicas, evolutivas y terapeuticas diferenciales. Nuestro objetivo fue describir la utilizacion de recursos terapeuticos y sanitarios en pacientes con PU en remision clinica. Material y metodos Estudio observacional retrospectivo en el que se incluyo a pacientes con PU en seguimiento en nuestro centro dentro del periodo 1989-2014. Se registraron las caracteristicas y evolucion clinicas, los tratamientos utilizados y las diferentes galenicas para el mantenimiento de la remision de la enfermedad. Resultados Se incluyo a 101 pacientes con PU, con una mediana de seguimiento de 8 anos (IIC: 3-14). El tratamiento de mantenimiento mas utilizado fue la mesalazina topica (89%), mayoritariamente en forma de supositorios. Un 55% de los pacientes siguieron en algun momento mesalazina oral. El 33% siguieron tratamiento combinado con mesalazina oral y topica, el 12% utilizaron corticoides topicos para el mantenimiento y solo el 3% requirieron tiopurinas. El 10% de los pacientes consultaron alguna vez al Servicio de Urgencias y solo el 4% requirio ingreso hospitalario por actividad de la PU durante el seguimiento. Ninguno de ellos preciso colectomia. Conclusiones La mesalazina topica constituye la terapia de mantenimiento mas empleada en la PU en nuestra practica clinica, lo que indica una buena aceptacion por parte de los pacientes y un elevado grado de confianza por los medicos prescriptores. La PU se asocia a una baja utilizacion de recursos sanitarios, pero serian necesarios estudios de su impacto en la calidad de vida.

Background Crohn disease (CD) and Ulcerative colitis (UC) are characterised by episodes of exacerbations and remissions. Monitoring disease activity based on intestinal lesion is mandatory prior to any change in the therapeutic strategy. Colonoscopy is the gold standard technique to monitor the disease activity in IBD patients, but it is usually discarded because of costs and risk issues. The concentration of Faecal Calprotectin (FC) is widely used as a non-invasive marker of inflammation of the intestinal mucosa, allowing the assessment of the disease activity. Recently, different studies have demonstrated that certain microbial species, part of intestinal microbiota which can be detected in stool samples, are capable of correlating with disease activity in CD and UC patients. The purpose of this study was to analyse the correlation between these microbial indicators and the FC to monitor the disease activity in CD and UC patients. Methods FC levels were used to define inflammatory disease activity, the predetermined cut-off of 250 μg/g of faeces was used, higher values indicated an active inflammation and lower values indicated disease in remission. Two cohorts consisting of 61 patients of CD (25 with active inflammation and 36 with remission) and 90 of UC (42 with active inflammation and 48 with remission) were recruited by the Gastroenterology department of 4 Catalan hospitals. A sample of faeces was collected from each patient. FC and the following markers were quantified by qPCR: Faecalibacterium prausnitzii (Fpra), Escherichia coli (Eco), Akkermansia muciniphila (Akk), Ruminococcus sp. (Rum), Bacteroidetes (Bac) and Methanobrevibacter smithii (Msm) for each sample. Results The bacterial markers presented different behaviour depending on the disease analysed. The abundances of Eco and Bac were higher in CD with active inflammation compared with CD with remission. In contrast, no significant differences were found for Fpra, Akk, Rum, and Msm. Besides, a significant positive correlation between Eco abundance and FC levels (0.280, p = 0.029) and a significant negative correlation between Msm and FC levels (−0.299, p = 0.021) were observed. According UC patients, while the abundance of Eco was higher in patients with active inflammation, the abundance of Rum was significantly less abundant. No significant differences were found for Fpra, Akk, Bac, and Msm. Moreover, we also observed a significant negative correlation between Rum and FC levels (−0.308, p = 0.003, respectively). Conclusion The abundance of Eco and Msm in CD patients and the abundance of Rum in UC patients correlate to FC in order to determine inflammatory disease activity. So, these markers can also be an accurate discriminator of active disease in CD and UC patients.

Background Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases these drugs are contraindicated or have previously failed. Recently, ustekinumab was licensed for CD but no data on its efficacy in the prevention of POR is still available. Methods All CD patients in whom ustekinumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a prospectively maintained database of the Spanish Working Group in IBD –GETECCU-). We evaluated the rates of endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score >i1 and advanced endoscopic POR by >i2. Results Thirty patients were included; ustekinumab was started after a median time of 60 days (IIQ 31–90). Concomitant immunosuppressants were used in 17%, 27% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 23% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. In total, 36% of them had more than one risk factor. 50% had been exposed to ustekinumab prior to the index surgery (46% within the last 6 months). The median time of follow-up on ustekinumab was 17 months (IQR 11–21). Fifty-six per cent of patients had at least one endoscopic assessment within 18 months after surgery: 58% had endoscopic POR and 23% advanced endoscopic POR. Additionally, 13% presented clinical POR at the discretion of the treating physician and none developed surgical POR. Conclusion In a small clinical practice cohort, ustekinumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR. Unfortunately, the lack of early endoscopic monitoring is still frequent despite the recommendations from guidelines.