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Background The management of inflammatory bowel disease (IBD) has substantially changed in the last decades, both in relation to medical and surgical treatments. Aims Principal: To know the rate of surgery in a newly diagnosed IBD cohort within the first year after diagnosis. Secondary: To describe the type of surgeries and indications in this cohort, and to identify predictive factors for surgery (focused on intestinal resection) in these patients. Methods Prospective, population-based nationwide registry. Adult patients diagnosed with IBD -Crohn’s disease (CD) and ulcerative colitis (UC)- during 2017 in Spain were included and were followed-up for 1 year. Kaplan-Meier curves were used to calculate the rate of surgery. In patients with intestinal resections, only medical treatments before surgery were considered. Predictive factors for surgery were identified by Cox-regression analysis. Results 3,454 patients (1,647 CD and 1,807 UC) were included (table 1). The incidence rate for surgery was significantly higher among CD patients (figure 1). A total of 197 patients (6%) underwent surgery within the first 12 months: 126 (64%) intestinal resections, and 71 (36%) perianal surgeries. Fifty-seven percent of intestinal resections were urgent, and 43% elective. The main indications for intestinal resections were: intestinal obstruction in 37%, abscess/fistula in 27%, perforation/acute abdomen in 25%, and refractoriness to medical treatment in 18% of cases. A total of 174 CD patients (10.6%) underwent surgery ¾61% intestinal resections and 39% perianal. Twenty-three UC patients (1.3%) were operated on; the number of surgeries in UC was too low to identify predictive factors. In CD patients, to have been treated with thiopurines [Hazard ratio (HR)=0.2, 95% confidence interval (CI)=0.1–0.3) was associated with lower likelihood of intestinal resection. Disease behaviour at diagnosis [stricturing vs. inflammatory (HR=6.5, 95%CI=4–10) and fistulising vs. inflammatory (HR=13, 95%CI=9–21)] was associated with the risk of intestinal resection. Biologic treatment was not associated with the likelihood of intestinal resection (figure 2). Conclusion Six percent of IBD patients undergo surgery within the first year of diagnosis, being higher in CD (11%) than in UC (1.3%). Sixty percent of intestinal resections are urgent procedures. The risk of surgery is increased in CD patients with fistulising and stricturing behaviour. Thiopurine, but not biologic treatment, is associated with lower risk of surgery.

Background The urinary metabolome of patients with Crohn’s disease (CD) differs significantly from healthy subjects and, among other features, reflects the specific gut dysbiosis affecting these patients. However, most of the studies included established and treated CD patients. Our aim was to characterize the urinary metabolome of onset and treatment-naïve CD patients and to identify the metabolic profile related to the different CD clinical classifications. Methods Patients newly diagnosed with CD (n=131) were prospectively included. Control healthy subjects (HC, n=338) were recruited among the general population and matched for sex, age and BMI to the IBD subjects. Fasting urine was obtained before starting any treatment. Metabolomic analysis was performed by proton nuclear magnetic resonance (1H NMR). We performed a comparative assessment of the urinary metabolome profile using a linear regression model for each metabolite, including sex, age, BMI, and smoking habit as covariates to control for confounding. The different subgroup comparisons within CD were made as follows: (1) CD; (2) CD location (Montreal Classification): L1 (ileal) + L4 (ileal and upper-intestinal), L2 (colonic) and L3 (ileocolonic); (3) endoscopic CD activity: 0, 1, 2 and 3; and (4) CD phenotype: B1 (inflammatory), B2 (stricturing) and B3 (penetrating), versus HC. In addition, data analysis was carried out using partial least squares-discriminate analysis (PLS-DA) to determine class membership based on distinct metabolomic profile. Results The primary characteristics of the CD patients and HC are shown in Table 1. Several metabolites were identified to be differently abundant in each group (Table 2). These metabolites are involved in relevant processes related to energy and aminoacids metabolism, and also include gut-derived metabolites. The PLS-DA model separated patients within the different clinical subgroups (Figures 1–4). Figures 1–4(b) show the main metabolites involved in each group separation. Many of these metabolites are in accordance with the differential metabolites obtained using the univariate analysis (Table 2), showing the potential of this approach to group CD patients and to identify potential biomarkers. Conclusion Analysis of urinary metabolites can help to understand the etiopathological mechanisms in CD. It has the potential to provide a non-invasive means of diagnosing CD, and can differentiate between CD clinical expressions.

Background Ustekinumab (UST) intensification during Crohn’s Disease (CD) treatment is becoming common in clinical practice. Little is known about early intensification maintenance regimens and their drug levels utility in discriminating CD-response and the need for further intensification. We aim to analyze UST levels’ evolution in an intensified maintenance regimen, their capacity to discriminate response according to inflammatory parameters and indicate the need for further intensification. Methods This is a retrospective study with 43 moderate/severe active CD patients (Harvey-Bradshaw Index [HBI] ≥4 and Fecal Calprotectin [FC] >250 µg/g) who received UST induction treatment (induction dose of 6mg/kg IV, plus dose of 90mg SC at week 8). Patients received maintenance treatment (90mg SC/8 weeks) and were followed for 52 weeks. They were classified according to the response obtained at the first year in responders (R), HBI 250µg/g; and intensification group (IG), partially responders that needed UST intensification to every 4 weeks. HBI, FC, C-Reactive Protein (CRP), and UST levels data were collected at baseline (w0), week 8 (w8), week 16 (w16), and 52 weeks (w52) of maintenance. IG was followed 12–26 weeks after intensification (aI). Results Half of the patients (48.8%) were male. Most of them (97.7%) have received previous anti-TNF-α treatment (53.49% ≥2 anti-TNF-α). Patients’ median age at the moment of starting UST was 51 (37.5, 58.5) years. Median disease duration was 11 (7.5, 23) years. Location of disease was ileal in 30% of patients and ileocolic in 53%. One-third of patients suffered perianal disease, and 41 % were smokers. The only demographic factor associated with non-response was ileocolic location. Table 1 shows the evolution of inflammatory parameters and UST levels according to the response. A Pearson correlation (r=0.62) between higher FC drop (baseline-w16) and higher drug levels at w16 was observed. The evolution of biological markers discriminates NR during induction; however, neither biological markers nor UST level can distinguish between R and those who will need intensification. R shows higher UST levels at w52 compared to IG. IG showed a significant increase of UST levels (mean of 5.39 points) and a substantial drop of FC and HBI (mean of 115.62 and 2.27 points, respectively) after intensification. Those patients reported clinical improvement; however, they could not reach a FC Conclusion FC drop-slope is associated with higher levels of UST at the end of induction. UST levels at w52 are useful for discriminating patients who will benefit from UST intensification every 4 weeks.

Background Despite the continuous adaptation of eHealth systems for patients with inflammatory bowel disease (IBD), a significant disconnection persists between users and developers. Since non-adherence remains high, it is necessary to better understand the patients’ perspectives on telemonitoring for IBD. The aim of this study was to adapt the TECCU app to the preferences and needs of IBD patients. Methods A qualitative study was carried out using successive focus groups of IBD patients. Meetings were audio-recorded and a thematic analysis approach was employed until data saturation was achieved. The first group included patients who had used the TECCU app in a pilot clinical trial, and subsequent meetings included patients with Crohn’s disease and ulcerative colitis recruited from the Spanish Confederation of patient associations. The information collected at each meeting guided consecutive changes to the platform. Results Data saturation was reached after 3 focus groups, involving a total of 18 patients. Three main themes emerged: (1) platform usability; (2) the communication process; and (3) contents of the platform. All participants indicated that TECCU is easy to use, permitting continuous and personalised feedback. Nevertheless, the platform was adapted according to the patients′ perspectives to foster a flexible follow-up and shared decision-making, using open and safe communication networks. Many participants appreciated the educational elements and the app was connected to reliable and continuously updated webpages. Conclusion IBD patients valued the usability and personalised monitoring offered by the TECCU App. Improvements in the messaging system and continuous updates of the educational contents were performed to address patients′ needs and favour their engagement.

Background Therapeutic drug monitoring (TDM) is used in inflammatory bowel disease to guide dosing of biologics to individualise drug exposure and optimise outcomes. In case of undetectable levels of Adalimumab (levels Methods Since October 13 to August 19, 758 TDM were performed in 260 patients treated with ADA. We selected the patients who had at least a level Results We identified 46 patients with undetectable levels; 12 were excluded. Thirty-four patients were included, 29 (85.3%) with Crohn’s disease and 5 (14.7%) with ulcerative colitis. Ten (29.4%) patients had combined treatment and 17 (50%) had previously received another anti-TNF. In 24 (70.6%) TDM was performed proactively. After detection of levels 5 μg/ml), 12 (60%) in the intensified-patient group and 2 (14.3%) in the group in whom the treatment was not modified. ADA was withdrawn in 13 patients (32.8%) after a mean time of 358 days (SD 258). The ADA maintenance rate (HR=3.88; 95% CI 1.2–12.4; p = 0.02) and the recovery ratio of ADA levels (HR = 6.75; 95% CI 1.1–39, 8; p = 0.03) was higher in the intensified group. Hypoalbuminemia was associated with an earlier withdrawal of ADA (p = 0.03) Conclusion The intensification of ADA in patients with IBD and undetectable plasma concentrations allows recovery of levels and maintenance of the drug in a high percentage of patients. The decision to withdraw treatment in patients with undetectable levels should be individualised.

Background & aims: Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Methods: Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (K index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. Results: 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p < 0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (kappa = 0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Conclusions: Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Background Few data are available on the efficacy of methotrexate (MTX) in ulcerative colitis (UC). Aim To evaluate the efficacy and safety of MTX in UC patients. Patients and methods UC patients who had been treated with MTX were identified from the databases of 8 Spanish IBD referral hospitals. Patients were included in the study if they received MTX for steroid dependency or steroid refractoriness. Therapeutic success was defined as the absence of UC-related symptoms, complete steroid withdrawal and no requirement of rescue therapies within the first 6months after starting MTX. Results Forty patients were included, 70% treated for steroid dependency and 27% for steroid refractoriness. Thiopurines had been previously attempted in 87.5% of patients. The median dose of MTX used for induction was 25mg (IIQ 17.5–25) weekly given parenterally in 82.5% of cases. Eighty-five percent of patients were on steroids when MTX was started. Forty-five percent of patients met criteria for therapeutic success. Initial treatment failures were mainly due to inefficacy (50%) or intolerance (36%). After a median follow-up of 28months (IQR 22–47), 38% of patients with initial therapeutic success required new steroid courses, 22% started biological therapy, and only 1 patient required colectomy. The cumulative probability of maintaining steroid-free clinical remission was 60%, 48%, and 35% at 6, 12, and 24months after starting MTX, respectively. Eleven patients (27.5%) experienced adverse events, leading to MTX discontinuation in only 8 of them. Conclusions MTX appears to be effective to maintain clinical remission in UC, at least in the short-term, with an acceptable safety profile.

Background Epidemiological studies have shown a greater prevalence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) among first-degree relatives of patients diagnosed of these diseases. However, it is not known whether relatives of patients with IBD have a greater prevalence of IBS than the general population. Aims To analyse the prevalence of IBS among first-degree relatives by consanguinity (parents, siblings and offspring) and affinity (spouses) of patients with IBD. Materials and methods A prevalence study was conducted identifying 490 relatives of 91 patients with IBD. Of these, 404 met inclusion criteria; and 360 (response rate: 89.1%) answered the questionnaires. Subjects were invited to participate in the study through index cases (patients with IBD). The following variables were collected: age, sex, history of digestive diseases, kinship and cohabitation with the index case. The relatives completed a questionnaire to identify those who met Rome I and Rome II criteria for IBS. Results The overall prevalence of IBS among the first-degree relatives of patients with IBD was 49.4% and 10% according to Rome I and Rome II criteria respectively. IBS prevalence was higher in first-degree blood relatives than in spouses of patients (Rome I: 53.1% vs 29.1%, p=0.001; Rome II: 10.8% vs 5.4%, NS). No differences were found in IBS prevalence depending on whether relatives were living with the index case or not. Conclusion IBS prevalence in first-degree relatives of patients with IBD is elevated. It is significantly greater in blood relatives, which suggests involvement of genetic and psychological factors rather than environmental factors.

Treatment with antitumor necrosis factor-alpha (anti-TNF-α) offers a significant improvement in several immune-based diseases, including Crohn's disease (CD) and psoriasis. Different cutaneous side effects have been described for anti-TNF-α therapy such as psoriasis. Previous reports showed that inhibition of TNF-α can induce over expression of cutaneous IFN-α, which in turn caused a predisposition to psoriasis. We report a 31-year-old woman with extensive CD and perianal lesions, without response to conventional treatment. She paradoxically developed a cutaneous eruption with psoriasiform morphology and distribution during treatment with both anti-TNF-α approved in Europe for CD, infliximab and adalimumab. These lesions cleared after topical application of corticosteroids and cessation of the anti-TNF-α treatment. Due to uneffectiveness of pharmacological treatment on disease, the patient had to undergo surgery. TNF-induced psoriasis in patients with CD is rare and has been previously documented with infliximab or adalimumab. The reason for this apparently paradoxical effect of the therapy is still unclear. This is the first case of psoriasis induced first by infliximab and later by adalimumab in the same CD patient. We would like to review and to draw attention about psoriasis as a cutaneous side effect with anti-TNF-α treatments.

at least one additional ICR. Therefore a group of patients with repeatedly performed ICR (ICR > 1) and a group with only one ICR (ICR = 1) were defined. Mean time until first ICR significantly varied between the groups, being 6.58 years in the ICR = 1 group and 4.80 years in the ICR > 1 group (Figure 1). Mean time to second ICR was 6.1 years. RFs for a second ICR determined in univariate analysis are shown in Figure 2. Non stricturing, non penetrating disease and IMT within 1 year after ICR were significant protective factors, while penetrating behaviour and ileal location were significant risk factors. In the multivariate logistic regression, only ileal disease (OR 3.07 [1.22;7.72], p = 0.02) was a significant RF. IMT at time of or within one year after first ICR (OR 0.23 [0.07;0.79], p < 0.01) presented as significant protective factors in the logistic regression.

surgery was 40.4% at one year and 59.3% at two years with a median time to surgery of 22 months (range 0.5 84 months). Patients who were steroid refractory, or dependent, prior to starting tacrolimus were more likely to have surgery (P= 0.006), while patients who were able to achieve or maintain a clinical response with tacrolimus by 90-days were less likely (P= 0.004). Conclusions: Tacrolimus is able to induce a clinical response in a third and remission in a fifth of medically refractory IBD patients at one year. A 90 day therapeutic trial is worthwhile in difficult to treat patients.

Results: Chronic DSS colitis induced persistent thickening of the muscularis propria (MP) with infiltration of vimentin+ cells in the chronic phase but not in acute colitis. Moreover, a mucosal healing response was associated with more cycles and recovery. Myofibroblasts (vimentin+ a-SMA+) were present in the submucosa (SM) in the chronic phase and not in the acute model. Differential deposition of collagen I and III was observed: collagen I was present in the SM around vimentin+ cells. Collagen III deposition in the SM started in the acute phase, further increased in chronic colitis with infiltration of collagen III between smooth muscle cells of the MP, to intestinal stricture formation in CD. During prolonged recovery there was a decrease in collagen III. Tenascin expression was scant in control colon but was clearly present in the mucosa and SM in the acute phase in individual cells. A linear deposition of tenascin around the crypts was also seen as expected in acute colitis. The linear deposition in the mucosa and submucosal spots persisted after 2 cycles of DSS, correlating with persisting tissue damage. The expression of tenascin decreased after 3 cycles and more so after additional recovery, in association with the disappearance of tissue damage. Conclusions: The connective tissue changes observed in chronic murine colitis induced by repeated cycles of DSS reflects tissue remodeling as seen in CD. The technical ease and reproducibility of the DSS model and ability to induce it in mice of a common inbred strain makes it an attractive model to study the connective tissue changes occurring in IBD.

P090 Restoration of health in patients with inflammatory bowel disease and mucosal healing F. Casellas Jorda1 *, M. Barreiro-de Acosta2, M. Iglesias2, V. Robles1, P. Nos3, M. Aguas4, S. Riestra5, R. De Francisco5, M. Papo6, N. Borruel1. 1Hospital Vall D’Hebron, Barcelona, Spain, 2University Hospital, Santiago De Compostela, Spain, 3La Fe Hospital, Instituto De Investigacion Sanitaria, Valencia, Spain, 4La Fe Hospital, Valencia, Spain, 5Hospital Universitario Central De Asturias, Inflammatory Bowel Disease Unit, Oviedo, Spain, 6Hospital Joan XXIII, Tarragona, Spain

ileocolonoscopy at diagnosis. Of the 276 patients not receiving an ileocolonoscopy at diagnosis, 80 did in follow-up. CD pts underwent significantly more ileocolonscopies at diagnosis, compared to UC pts (44% vs 17%, p < 0.001) and IBDU pts (44% vs 4.5%, p = 0.001). Reasons for follow-up endoscopy were: relapse of symptoms (76%), evaluating treatment effect and/or disease extension (22%) and cancer surveillance (2.4%). In 71% of the follow-up endoscopies active inflammation was seen, however this led to treatment intensification in only 65%. Conclusions: Endoscopies is an often used tool in IBD patients, although only 29% patients received an ileocolonoscopy at diagnosis. Fourty-five percent of the endoscopies performed at follow-up led to treatment intensification, but in over one third of endoscopies showing inflammation, no adjustments were made.