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

Background Ustekinumab has been recently approved for the treatment of moderately to severe ulcerative colitis (UC). Data from the UNIFI clinical trial are encouraging; nevertheless, real-world assessment is needed. We assess the effectiveness, safety and pharmacokinetics of ustekinumab in a cohort of refractory UC patients. Methods Multicentre and observational study of UC patients who received ustekinumab for active disease. Values for Partial Mayo Score (PMS), endoscopic activity, C reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8, 24 and 52 weeks and at 18 and 24 months when was possible. Demographic and clinical data, previous treatments, adverse events (AEs), surgeries and hospitalizations were documented. Possible predictors of response were examined. Results One hundred and eight patients were analyzed (Table 1). Two patients only received the first IV dose. During follow-up, 58 patients (54%) required interval reduction (every 4 weeks (76%) and every 6 weeks (24%)) after a median of 22.3 weeks [11.6, 41.2]. Intravenous reinduction doses were administered to 20 (18.5%) after 27.7 weeks [6.64, 56.3]. Three patients required a maintenance therapy with IV administration. The clinical remission (PMS≤ 2) rates were 39.6%, 41%, 51% at 8, 24 and 52 weeks, respectively, and 61%, and 57.7% at 18 and 24 months, respectively. FC levels returned to normal ( Fewer previous anti-TNF agents and the loss of response to anti-TNF were associated with clinical response and with normalization of FC respectively. No variables at baseline (body mass index, serum albumin, and lymphocytes count) were associated with ustekinumab through levels. Of the 17 patients with endoscopy before and after treatment, 6 were in remission and 3 with mild activity. The AEs were recorded in 5 (4.6%) patients, 12 (11%) were hospitalized and 9 (8.3%) had surgery. A total of 23 patients (21%) discontinued ustekinumab over time, the persistence rates were 98%, 91%, 83% and 81% at 8, 24, 48 and 96 weeks respectively. Conclusion This is the first study to show the real-world long-term effectiveness, persistence, endoscopic improvement and safety of ustekinumab in a cohort of highly refractory UC patients. The clinical remission preceded the FC normalization. Ustekinumab through levels and their pharmacokinetic require further investigations.

Background Vedolizumab is one of the current treatments for patients with inflammatory bowel disease (IBD). The efficacy and safety, along with its gut specificity, make this drug an appealing therapeutic option for IBD patients with moderate to severe disease. However, as observed for other biologic treatments, a significant proportion of patients do not have an initial response to vedolizumab treatment. Currently, there is a lack of reliable predictive tools for vedolizumab treatment response, although this would help to alleviate the socioeconomic costs derived from this disease. For that reason, the primary aim of this study is to show putative transcriptional signatures associated with vedolizumab treatment response. Methods For the realization of this study, we used RNA-seq datasets from the Gene Expression Omnibus (GEO) database: GSE191328. This dataset includes samples from peripheral blood cells from responder and non-responder ulcerative colitis (UC) patients treated with vedolizumab and infliximab at baseline. Gene Set Enrichment Analysis (GSEA) was performed to compare the differential expression and the enrichment analysis was calculated using ssGSEA of the different groups under study. Results The analysis of the transcriptome of peripheral blood cells from responder (R) and non-responder (NR) vedolizumab-treated patients at baseline revealed interesting enrichment results. We found 20 gene sets positively enriched in NR versus R and only 9 gene sets negatively enriched in the same phenotypes. In order to find vedolizumab specific transcriptional signatures, we performed a similar analysis in samples from infliximab-treated patients. After that second round of analysis, we observed that around 50% of the enriched gene sets were similar for both biological treatments. Nevertheless, several interesting biological functions such as peroxisome function, reactive oxygen function or beta-catenin signalling are specifically enriched in NR patients to vedolizumab treatment. Conclusion Our data suggest that vedolizumab NR patients specifically show a transcriptional enrichment profile, which differs from vedolizumab R patients. Also, the comparative analysis with infliximab-treated patients reveals that those specific transcripts are modulated in response to this α4β7 integrin antibodies in peripheral blood cells. Therefore, we found a solid system to search for vedolizumab therapy predictive response markers using low invasive techniques.

Background The role of occupation is well established for different diseases. Nevertheless, there is a lack of information on the role of occupation on the onset of inflammatory bowel diseases. Many occupations entail the exposure of different toxic substances that may reach the bowel through different biological pathways (bloodstream or digestive tract) and act as possible triggers of such diseases, mainly Crohn′s disease and ulcerative colitis. The aim of this study is to identify if there is a role of occupation on the onset of IBD using a case-control study. Methods A prospective case-control, single-center study was designed. All Incident cases with any of the main IBD diseases (ulcerative colitis, Crohn’s disease and unclassified colitis) were consecutively included. Controls were patients selected from the consults and endoscopic room of the Digestive Unit of Clinical Hospital of Santiago de Compostela without any autoimmune chronic disease. Cases are patients with IBD disease diagnosed 3 or less months prior to the inclusion and over 18 years old. Cases and controls were recruited simultaneously and controls followed a sex and age frequency matching with cases. All participants were recruited from June 2020 to September 2022. A detailed questionnaire describing the occupations held and time of them was used. Blue-collar jobs have been defined as those entailing the highest risk occupational exposures and are also mentioned as manual workers. White-collar jobs are usually those with more office-related work, but also with teaching or health sector. To analyze the results, we used a logistic regression. A subgroup analysis was performed by each of the three diseases considered. Results 129 patients with incident IBD (73 with ulcerative colitis, 51 with Crohn’s disease and 5 with indeterminate colitis) and 114 controls were included. Comparing patients with IBD with controls, there were no statistically significant differences between type of work, working hours, contact with animals or physical activity at work. Among the patients with IBD, there were no differences in the number of flares between groups (blue collar workers vs. white collar (p>0.05), outside workers vs. indoor ones (p>0.05), sedentariness vs. moderate activity or high activity (p>0.05) or animal contact vs. no contact (p>0.05)). Taking into account only patients with current work activity, the results did not change. After stratifying results according to type of IBD, there were no statistically significant differences either (table 1). Conclusion In this study, differences between type of work, working hours, contact with animals or sedentariness were not associated with the risk of IBD nor with the activity of this disease.

Background Fatigue is a significant predictor of worst health-related qualify of life in inflammatory bowel disease (IBD) patients. Nevertheless, the role of fatigue in IBD patients under infliximab (IFX) therapy has been poorly investigated. The aim of the study was to evaluate the potential factors associated with fatigue in patients under maintenance treatment with IFX. Methods A prospective observational cohort study was designed. All IBD patients aged 18 and over under maintenance treatment with intravenous (IV) infliximab were consecutively included at the infusion day. Patients completed 3 self administered questionnaires. Fatigue was assessed with the Fatigue Impact Scale (FIS), quality of life with the Inflammatory Bowel Disease Questionnaire-Short From (IBDQ-9) and anxiety and depression using the Hospital Anxiety and Depression scale (HAD). We considered the maximum total FIS as the highest fatigue perception. Disease activity was defined in Crohn’s disease as a Harvey-Bradshaw index >4, and in ulcerative colitis (UC) as a Partial Mayo index >2. Patient demographics and disease characteristics were also collected: age, sex, disease duration, smoking habit, type of IBD, extra-intestinal manifestations, clinical activity, prior surgery, obesity, anemia, treatments (steroids, immunosuppressants, anxiolytics, antidepressants) and presence of anxiety or depression. Multiple linear regression was used to identify the variables associated with the presence of fatigue. Results Ninety patients were consecutively included (49 female, median age 42 years, interquartile range 19). Sixty three patients (70%) had Crohn’s disease (46.8% fistulising and 25.8% stenosing behaviour) and twenty seven ulcerative colitis (30%). Nearly 27% were smokers, 35 (39%) presented anxiety and 18 (21%) depression. Approximately, 8% of the patients and 7% received treatment for anxiety and depression, respectively, but only 2/18 patients with current depression received antidepressants. Combotherapy was present in 41% of the patients and 75.6% were in clinical remission. Mean fatigue was 32.74 ± SD 17.27. The highest scores for fatigue were associated with female gender (B = 10.936; P= 0.009) and the presence of depression (B = 11.114; P = 0.029). Activity disease almost increased significantly the severity of the fatigue(B = 8.995; P= 0.063). The use of antidepressants not increased the risk (B = -4.995; P = 0.555). Patients with fatigue had significantly reduced the quality of life (r = -0.638; p < 0.001) (Figure 1). Conclusion Uncontrolled depression and female gender increased the risk of severe fatigue more than disease activity in patients under maintenance treatment with IFX. Fatigue is related to worst health-related qualify of life.

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 Pouchitis and other inflammatory disorders of the pouch (IDP), such as Crohn′s-like disease of the pouch (CDP), are frequent in patients operated for a previous diagnosis of ulcerative colitis. Many different therapies have been used, but the effectiveness of immunosupresants (IMM) has been poorly explored in this setting. Our aim was to evaluate the use, efficacy and safety of IMM in patients with pouchitis or another IDP. Methods Retrospective and multicentric study of a Spanish cohort of pouch-carrying patients with previous diagnosis of ulcerative colitis, and subsequent diagnosis of IDP, following ECCO diagnostic criteria. Patients who used IMM to treat these conditions were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission, and non-response as no improvement or worsening symptoms. Endoscopic response was evaluated when possible using modified pouchitis disease activity index (PDAI) endoscopic subscore. Adverse events were collected. We used descriptive statistics. Results In the overall cohort of 338 patients with IDP, 93 (27%) were treated with IMM. Of those, 57% males, median age 40 (20-71) ys, and 72% non-smokers. Colectomy was performed at a median age of 31 (18-63) ys and IPD was diagnosed 25 (1-235) months after ileostomy closure. IMM used were thiopurines (n=86), methotrexate (n=4), cyclosporine (n=2) and tacrolimus (n=1). IMM were used as monotherapy in 66 (71%) cases and were indicated as treatment of pouchitis (n=60, 65%), CDP (n=32, 34.4%) and cuffitis (n=1, 1%). Effectiveness was evaluated only for thiopurine monotherapy (n=62). After a median follow-up of 23 (1-234) months, clinical remission was achieved in 31%, clinical response in 31% and non-response in 38% (Figure 1). There were no differences in effectiveness between pouchitis and CDP (63.9% vs 57.7%, p= 0.62). Endoscopic response was evaluated in 19 (30.6%) cases. After a median of 9 months of follow-up median PDAI endoscopic subscore dropped from 3 (range 2-4) to 1 (range 0-3), (Figure 2). Adverse events related with treatment appeared in 28 patients (45%). Thiopurines were discontinued in 39 cases (63%) due to failure (17), toxicity (16) and long remission (6 cases). Conclusion In our cohort, thiopurines were used in 27% of patients with IDP, with long-term benefit (remission or response) in around two-thirds of them. This therapy could be one more option to manage these disorders.

Background Pouchitis and Crohn′s-like disease of the pouch (CDP) can be refractory to conventional therapy. Evidence of biological therapy has been rarely reported in large patient cohorts. We explored the use and effectiveness of these therapies and compared the success of a second biologic after antiTNF failure. Methods This is a retrospective RESERVO study of the Spanish cohort of GETECCU, that included patients operated for ulcerative colitis, with pouch construction, and subsequent diagnosis of pouchitis, CDP or cuffitis second ECCO diagnostic criteria1. Patients treated with antiTNF, Vedolizumab and/or Ustekinumab were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission and non-response as no change or worsening of these symptoms. We also compared the effectiveness of second biologic (antiTNF vs vedolizumab-ustekinumab) after antiTNF failure, using descriptive and comparative statistics. Results The cohort comprised 145 patients. Demographic and clinical characteristics are represented in Table 1. A total of 232 biologic therapies were indicated. Of the total cohort, 60 (41.3%), 21 (14.4%) and 6 (4.1%) used two, three and four lines, respectively. Biologics used were Infliximab (n=95), Adalimumab (n=69), Vedolizumab (n=35), Ustekinumab (n=26) and Golimumab (n=7). Therapy characteristics, clinical effectiveness, need for intensification, discontinuation, and therapy duration for each biological therapy are represented in Table 2. Global rates of clinical remission, response, non-response and loss of response to a first biologic were 21.8%, 27.5%, 21.1% and 29.6%. Female gender was the only factor associated with effectiveness to a first biologic in univariate analysis (OR 2.16, CI 1.08–4.32, p 0.027). There were no significant differences regarding efectiveness between type of pouch disorder (pouchitis vs CDP, 51.6 vs 47.6%, p 0.48) or biologic agents. Thirty-nine patients received a second biologic after prior antiTNF failure (28 a second antiTNF and 11 non-antiTNF: 6 Vedolizumab, 5 Ustekinumab). Basal characteristics in this subgroup showed no significant differences. Clinical response (21.4 vs 63.6%, p 0.02) and discontinuation therapy rates (82.2 vs 54.5 %, p 0.04) after 11 months showed a more favorable profile for non-antiTNF therapy. Conclusion Biologics represent an effective option in the management of pouchitis and Crohn′s like disease of the pouch. Despite our small sample size, non-antiTNF therapy could be the best option after antiTNF failure. 1Fernando Magro. J Crohns Colitis 2017; 11(6): 649–670.

Background Adalimumab (ADA) dose escalation from 40 mg SC every other week (EOW) to 40 mg weekly is approved for IBD patients with loss of response. A recently registered device containing 80 mg of ADA will allow an alternative dose escalation regimen with SC doses of 80 mg EOW. The ADASCAL study aimed to evaluate the preferences and satisfaction of patients with modifying the ADA regimen from 40 mg weekly to 80 mg EOW. Methods This multicentre cross-sectional study included patients with IBD in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW according to clinical practice. Patients who have received at least 4 doses of 80 mg EOW completed a 4-item self-questionnaire (a Likert-like 5-point scale for preferences, 2 closed questions for convenience, and a 100-point visual analogue scale [VAS] to evaluate patient’s preference for weekly or EOW ADA) (Figure 1); and the 14-item Treatment Satisfaction Questionnaire for medication (TSQM 1.4) that covers 4 domains: effectiveness, side effects, convenience, and overall satisfaction. Results Seventy-seven patients (64 CD, 13 UC; 67.5% men; mean age 48 years, SD 14.1) were included. The overall mean duration of exposure to ADA was 66 months (SD 34), with mean exposure to ADA 40 mg weekly of 40 months (SD 25), and mean exposure to ADA 80 mg EOW of 12 months (SD 5). At the time of the survey, 87.1% of CD patients and all UC patients were in clinical remission (Harvey-Bradshaw index ≤4 for CD, Partial Mayo score ≤1 for UC). According to the results of the questionnaires, 74% of the patients preferred the 80 mg EOW ADA regimen (59.7% had a strong preference and 14.3% had a slight preference) (Figure 1). Patients referred that ADA EOW regimen interferes less with daily activity and with travel plans. Most patients wanted to continue with ADA 80 mg EOW, as reflected by a mean VAS score of 84.7 (SD 24.1), where 0 indicated a choice for weekly ADA, 100 for ADA EOW, and 50 indifferent. Overall, 77% of patients preferred to continue with ADA EOW, 4% with ADA weekly, and 17% were indifferent. Attending physicians also reported a greater preference for the EOW ADA regimen (mean VAS score 93, SD 7.8). The mean global satisfaction according to the TSQM was 84.3% (SD 13.5), where 0 indicated extremely dissatisfied and 100 extremely satisfied. Patients reported very high TSQM scores for individual components: effectiveness 77.6% (SD 16.9), convenience 83.7% (SD 14.5), and side effects 86.1% (SD 23.4). Conclusion IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen. TSQM results indicated that patients had a high level of satisfaction with the current EOW regimen. Therefore, most patients wanted to continue with ADA 80 mg EOW.

Background Crohn’s disease (CD) is an inflammatory bowel disease with chronic course and exacerbations. Diagnosis and follow-up are based on clinical activity, biomarkers, ileocolonoscopy and imaging techniques. Intestinal ultrasound (IUS) has been shown to have high sensitivity and specificity analyzing inflammatory activity in CD. The aim of our study is to correlate IUS parameters with clinical activity and biomarkers in CD. Methods Retrospective, observational, single-center study was designed. Adult patients with CD who underwent IUS between September 2020 and May 2021 were included. Exclusion criteria was exclusive colonic involvement. Examination was done by ultrasound machine (Hitachi Ascendus) with low frequency curved-array (1–5 MHz) and high-frequency linear-array (5–13 MHz) transducers. Examination assessed bowel wall thickness, mesenteric fat hypertrophy, lymph nodes, hyperemia on color Doppler flow measured as Limberg index and length of affected segment (cm). Clinical activity score for CD was assessed by Harvey Bradshaw index (HBI). Biomarkers parameters studied were C-reactive protein (CRP) and faecal calprotectin (FC). Results are shown as percentages, median and interquartile range (IQR). Data were analysed using Spearman′s correlation analysis Results 121 patients were included (median age 45.6 years (IQR 33.4 – 59.6), 56.2% female). 78.5% had ileal disease and 21.5% ileocolonic involvement. At the time of IUS 17.4% of patients were not taking any maintenance treatment, 13.2% were on azathioprine, 48.8% on anti-TNF (61% adalimumab; 39% infliximab) and 8.3% on ustekinumab. 85.1% patients had HBI Conclusion Through this study, significant correlation between IUS and biomarkers was observed in CD. IUS has been shown to be useful for monitoring CD activity in order to optimize patients′ treatment.

Background Ulcerative proctitis may have a mild and less aggressive course, although evidence is scarce because these patients are excluded from participation in randomized controlled clinical trials. The aim is to identify clinical characteristics and complications associated with ulcerative proctitis refractory to conventional therapy. Methods Patients included in the prospectively maintained ENEIDA registry from GETECCU with ulcerative proctitis were included. Socio-demographic data were evaluated. We defined ulcerative proctitis based on ECCO guidelines and immunosuppression as the use of immunomodulators and/or biologics. Logistic regression was used to identify the independent factors associated with immunosuppressive therapy among the different socio-demographic data. Results From a total of 34.716 patients with ulcerative colitis, 6281 (18%) patients with ulcerative proctitis were identified. Mean age was 53 ±15 years and mean duration of illness was 12 ± 9 years. Surgery was necessary only in 2% of patients, 31 (0.5%) panprotocolectomy or subtotal colectomy. The clinical characteristics of the patients with and without immunosupressive therapy are summarized at table 1. A total of 3691 patients received oral 5-ASA (58.8%) and 4652 (74.1%) topic 5ASA. 636 (10.1%) were refractory to 5-ASA and corticosteroids, necessitating immunosuppression: 459 patients with azathioprine (7%), 28 with 6-mercaptopurine (0.4%), 49 with methothrexate (0.8%), 191 with infliximab (9%), 125 with adalimumab (2%), 50 with golimumab (0.8%), 57 with vedolizumab (0.9%), 6 with ustekinumab (0.1%) and 3 with tofacitinib (0.0). 316 (5%) patients needed one biologic therapy, 95 (1.5%) needed 2 biologics and 40 (0.6%) at least three different biologics. Longer duration of illness and use of corticosteroids were associated with higher risk of immunosuppression. Conclusion Good clinical outcomes were recorded in ulcerative proctitis, with only 10% of patients treated with immunosuppression therapy. The risk factors of immunosuppression were longer duration of illness and use of corticosteroids.

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 Despite the existence of specific recommendations, patients with inflammatory bowel disease (IBD) have shown low immunization rates. The aim of this study was to evaluate the adherence to vaccination recommendations by physicians to their IBD patients. Methods An online anonymous survey was sent to 8000 patients from a national patient association (ACCU-Spain). Three invitations were sent between October-December 2020. Questions were jointly designed by ACCU and GETECCU. Potential reasons for vaccination compliance were evaluated and analysed for different vaccines: age, gender, type of IBD, type of healthcare and treatments. Descriptive analyses and logistic regression were performed to identify factors associated with adherence to vaccination recommendations. Results 1302 patients with IBD responded to the survey (mean age 43 years [SD 12], 72% women). Forty percent of patients had ulcerative colitis, 58% Crohn’s disease and 2% indeterminate colitis. 91% of patients were treated in public facilities, 5% in a private setting and 4% in both. 41% of patients were treated with 5ASA, 35% with azathioprine/methotrexate, 50% with biologics and 8% with corticosteroids. Although [IRL1] [YZ2] physicians recommended vaccination, 45% were not adherent to papilloma virus vaccine, 18% to pneumococcus, 18% to hepatitis B vaccine, 16% to influenza and 12% to tetanus. The main reason for non-compliance to physician recommendation was considering that is not necessary (Table 1). Some factors associated to vaccine compliance are shown in Table 2. Conclusion Non-adherence to vaccination recommendations in IBD patients is frequent. Patients with immunosuppressive therapy show less compliance to the vaccination recommendations. The importance and benefits of vaccination needs to be explained to improve the adherence in IBD patients.

Background Lack of adherence in patients with inflammatory bowel disease (IBD) is a relevant problem in our clinical practice. Non-adherence to anti-TNF increases healthcare costs. The aim of this study was both to measure adherence and also to study the factors and consequences related to non-adherence in patients with IBD under maintenance treatment with infliximab (IFX). Methods A prospective, observational cohort study was designed and patients with IBD under treatment with IFX were consecutively included. Adherence was measured with pharmacy refills and Morisky Medication Adherence Scale-8 (MMAS-8). Patients were systematically asked about adherence and the mean displacement days, the accumulated delay, the mean delay and the medication possession ratio (MPR) were calculated. MPR was calculated by dividing the number of days supplied within the refill interval by the number of days in the actual refill interval over 24 months. Potencial risk factors for non-adherence were evaluated: age, gender, disease duration, site of disease, behaviour of Crohn’s disease (CD), smoking status, educational level, marital status, type of housing, extraintestinal manifestations, previous surgery, concomitant treatments, anxiety and depression. Relapse was defined as a Harvey Bradshaw score > 4 in CD and a partial Mayo > 2 in ulcerative colitis (UC). The Mann-Whitney Wilcoxon U Test was used to distinguish the intergroup differences. Correlations were evaluated with Spearman rank correlation coefficients. Results Ninety patients with mean age 46 years (range: 22–85) were included. 49 (54.4%) were women and 63 (70%) had CD. Anxiety occurred in 38.9% of patients and depression in 78.9%. Three quarters of the patients were in clinical remission at inclusion. After 24 months of follow-up, 82 (91.1%) had delayed some dose of treatment, 35 (38.9%) had delayed on at least 7 days some dose of treatment, and 11 (12.2%) had not received some of the scheduled doses. The MPR was 87% (range 46–100). Lack of adherence was related to loss of response to IFX in CD (p = 0.035), but not in UC (p=0.078). In UC, lack of adherence was related with anxiety (p=0.046). The Spearman’s correlation between older age and non-adherence was 0.53 (p=0.006) in UC and 0.1 (p=0.308) in CD. Conclusion Lack of adherence is related to loss of response to IFX in CD. Non-adherence to IFX is high and strongly associated with age in UC. Older patients with UC are more prone to lack of adherence.

Background The prevalence of penetrating disease in Crohn’s disease (CD) increases progressively over time, and evidence on the medical treatment of this complication is limited. The aim of this study was to evaluate the efficacy of biologic agents in CD complicated with internal fistulising disease. Methods A retrospective analysis of all adult patients from the ENEIDA registry (>68,000 patients) with CD who received at least one biologic agent -anti-TNF, ustekinumab or vedolizumab- for penetrating disease was performed. Exclusion criteria comprised treatment for perianal disease, enterocutaneous, anastomotic or periostomal fistula tracts. The main outcomes were fistula-related surgery and fistula closure on cross-sectional imaging. Preestablished secondary outcomes included the rate of abdominal abscess, the need for percutaneous drainage, the changes in the number of fistula tracts, fistula closure rates, and the safety profile.The baseline characteristics were analyzed by means of descriptive statistics and were compared by non-parametric tests. Predictive factors associated with surgery and fistula closure were evaluated by a multivariable logistic regression and survival analyses. Results A total of 710 patients (median age 38 years [IQR, 28-48], 59% male, 55% L3) receiving 791 biologic treatments were included at 53 sites (701 anti-TNF, 71 ustekinumab, and 19 vedolizumab). Patients had a median of 1 (range 1-5) fistula tracts, 49% of them entero-enteric followed by entero-colic (28%). After a median follow-up of 59 months (IQR, 27-105), 244 patients (31%) required surgery due to internal fistulising complications after 8.5 months (IQR, 3-24). Patients with ileocolonic disease (OR 1.99 [1.22-3.23]), entero-urinary fistulas (OR 2.35 [1.17-4.73]), or with a stricture distal to the fistula (OR 2.1 [1.31-3.36]) showed a higher risk of surgery, with no differences between biologic drugs (Figure 1). Combination therapy reduced the risk of surgery (HR 0.58 [0.37-0.90]). Fistula closure was observed in 24% of patients after a median of 15 months (IQR, 7.5-27). Patients with a lower number of fistula tracts showed a higher probability of closure (OR 1.72 [1.09-2.7]). Conclusion A high proportion of patients with internal fistulizing CD benefit from biologic treatment after a median of 5 years. During this follow-up, around two thirds of patients are free of surgery and one in every four patients achieves fistula closure.

Background Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

Background Crohn’s disease (CD) can develop fistulizing complications at any time during the disease course. Enterocutaneous fistulas (ECF) are disabling lesions with a significant impact on quality of life. The aim of this study was to describe the characteristics and natural history of ECF complicating CD, and to analyze its medical and/or surgical management. Methods A retrospective analysis of all adult patients with fistulizing CD with at least one episode of ECF from the ENEIDA registry (over 68,000 patients) was performed. ECF were defined as a communication between the gastrointestinal tract and the skin producing leakage of luminal contents. Additional data describing the ECF and its medical or surgical management were gathered. The main endpoint was any ECF-related surgical intervention. Fistula closure was defined as the absence of drainage, with no new abscess or surgery for at least 6 months. A comparison of the characteristics and outcomes after the availability of biologic agents (Jan/2000) was also performed. The baseline characteristics were analyzed by means of descriptive statistics and were compared by non-parametric tests. Factors associated with surgery were further evaluated in a binary multivariable regression and survival analysis. Results A total of 301 ECF in 286 patients from 46 hospitals diagnosed between Jan/1970-Sept/2020 were included (median age 34 years (IQR, 27–46); 59% male; 67% L3). ECF had a median of 1 external opening (range 1–10), 59% with concomitant internal fistulas, and usually involved the ileum (67%) or colon (23%). After 146 months (IQR, 69–233) of follow-up, 37% received thiopurines, 40% anti-TNF, 6% ustekinumab and 2% vedolizumab. Surgery was performed in 208 patients (69%) after a median of 4 months (IQR, 1.4–12). Fistula closure was achieved in 253 patients (84%) after 30 months (IQR, 4–84), mostly after surgery (54%) and in one third after medical therapy. Fistula recurrence was uncommon (11%) after closure. Patient and fistula characteristics were significantly different after the availability of biologics. In fact, anti-TNF biologics and thiopurines reduced surgery risk (HR 0.5; 0.38–0.67; HR 0.64; 0.47–0.86, respectively). The surgery rate in the biologic era tends to be lower than before (OR 0.63;0.33–1.09) while timing is similar. Closure rates are also comparable, but it was obtained more frequently after medical therapy once biologicals were available (OR 2.21; 1.13–4.29). Conclusion ECF complicating CD entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A number of patients can benefit from medical therapy and achieve fistula closure.

Background Patients with colon Inflammatory Bowel Disease (IBD) have a higher risk of colorectal cancer (CRC) than general population. Current guidelines establish endoscopic surveillance recommendations; however, epidemiological studies show poor compliance. The main aim of our study was to analyse adherence to endoscopic surveillance guidelines. Secondary aim was to evaluate the prevalence and time-to advanced lesions or CRC. Methods Retrospective multicentre study of patients with IBD followed-up in the participating centres between 2005 and 2020, who were diagnosed of IBD between 2005 and 2008, with criteria for CRC surveillance. Patients with CRC before IBD diagnosis were excluded. The ECCO 2013–2017 guidelines were used to evaluate adherence. Adenomatous lesions with >25% of villous component, >1cm or with high-grade dysplasia or serrated lesions >1cm or with any degree of dysplasia were considered advanced lesions. Software used for all analysis was R in its 3.6.1 version. Normality was checked with the Shapiro-Wilks test. Mean comparison was carried out using t-Student test while normality assumptions held true, otherwise, Mann-Whitney test. Time-to advanced lesions or CRC event between patients that had adherence to ECCO guidelines versus those who did not was performed through Kaplan-Meier and Log-rank test. P-values below 0.05 were considered significant. Results A total of 1004 (713 Ulcerative Colitis, 252 Crohn’s disease and 39 Indeterminate Colitis; 52% male) patients from 25 centres were recruited with a median age of 36 (26–47) years. 87% of all patients were included in the endoscopic surveillance programme. The main reasons for non-inclusion were the absence of indication by the physician (38%) and the presence of inflammatory activity (37%). Adherence to the first or subsequent surveillance colonoscopies was 45% and 61%, respectively, with a total adherence rate of 32%. Prevalence of advanced lesions or CRC was 4% and 7 cases of CRC were detected. Time-to-detection of these lesions since IBD diagnosis was significantly longer in non-adherent patients (13.4 + 1.3 vs13.04 + 1.7; p Conclusion Adherence to ECCO guidelines for endoscopic surveillance is low in this Southern European population. A higher and earlier detection of advanced lesions or CRC was identified in the adherent group. The results of this study highlight the need to improve compliance with the recommendations to obtain better outcomes.

Background Vedolizumab is one of the current treatments for patients with Inflammatory Bowel Disease (IBD). The efficacy and safety, together with its gut specificity, make this drug an appealing therapeutic option for IBD patients with moderate to severe disease. However, as observed for other biologic treatments, a significant proportion of patients do not have an initial response to vedolizumab treatment. Currently, there is a lack of reliable biomarkers for vedolizumab treatment response, although this would help to palliate the socioeconomic costs derived from this disease. For that reason, the primary aim of this study is to establish the basis for the search of transcriptional factors associated with vedolizumab treatment response. Methods For the realization of this study, we collected blood samples from responder and non-responder Ulcerative Colitis (UC) patients treated with vedolizumab. The clinical response was measured using the Partial Mayo Score. The frequencies of different immune system populations were analysed by flow cytometry. Moreover, we measured the transcriptional levels of several genes in peripheral blood mononuclear cells (PBMC) by RT-qPCR. These experimental procedures were performed at baseline (T0) and after 14 weeks of follow-up (T14). Results We enrolled nine patients with an average age of 46.25±11.71, of which seven were previously treated with anti-TNF therapy. Our results show a specific pattern in responder and non-responder patients in the percentages of different innate and adaptive immune cell populations at T0 versus T14. Similarly, we observed a significant reduction in the expression of some chemokines (i.e., CCL25) and pro-resolutive factors (i.e., ANNEXIN A1) at T14 versus T0 in PBMCs from vedolizumab responder patients, which was not observed in non-responder patients. Conclusion Our data suggest that the frequencies of certain immune populations are associated with the response to vedolizumab treatment. In the same way, we found that specific transcripts are modulated in response to this α4β7 integrin antibodies in PBMCs. Therefore, we found a solid system to search for vedolizumab therapy response markers using low invasive techniques.

Background Inflammatory Bowel Disease (IBD) is a multifactorial pathology with an increasing incidence. There are environmental factors, many unknown, that participate in its development. There is no study having assessed a possible relationship with residential radon exposure, which is very high in the study area. The aim of this study was to analyze if residential radon concentration measured at a municipal level is associated with a higher incidence of IBD and its characteristics (clinical or demographic). Methods We performed an ecological study where we included all incident cases of IBD in the area of Santiago de Compostela between January and December 2017 in order to estimate municipal incidence rates. Radon levels at a municipal level were obtained from the Galician Radon Map and correlated with demographic factors and type of IBD. We used the Spearman’s correlation coefficient to test the existence of any association. Results 96 patients were included, 63 (65.6%) with Ulcerative Colitis, 29 (30.25) with Crohn’s Disease and 4 (4.2%) with indeterminate colitis. Median age was 41 (IQR: 33.5 to 56 years), and 50.0% were women. The incidence rate per 100.000 inhabitants-year in the study area was 21.6 cases. The median radon concentration was 104.9Bq/m3 (IQR: 91.0 to 154.6), without statistically significant differences in function of the location of the house (rural vs. urban) nor the type of edification (flat vs house), p >0.05. There were no statistically significant differences on the type of IBD developed (ulcerative colitis, Crohn’s disease or indeterminate colitis) regarding radon levels either (p>0.05). There were no statistically significant differences (p>0.05) between radon and sex of IBD cases. No correlation between radon levels and age of the individuals was observed (Spearman’s rho = -0.13, p-value 0.2), nor radon levels variation by age groups (p>0.05). There was no correlation between radon concentration and cumulative incidence of IBD at municipal level (Spearman’s rho = 0.13, p-value 0.5), as it is shown in figure 1. Conclusion In the area of Santiago de Compostela there is a higher incidence of IBD in comparison with previous studies taking western countries as reference. It is possible that some environmental risk factors, could be responsible of this difference. In this study we have not found any correlation with municipal average radon concentration and incidence of IBD or any of its types.

Background Despite the existence of specific recommendations, patients with Inflammatory Bowel Disease (IBD) have shown low immunization rates. The aim of this study was to evaluate the management of vaccines in clinical practice in IBD from the perspective of physicians and patients. Methods An online anonymous survey was sent to 8000 patients from a national patient association (ACCU-Spain) and 1000 members of the Spanish IBD Working Group (GETECCU). Three invitations were sent between October-December 2020. Forty questions were jointly designed by ACCU and GETECCU in two different surveys for physicians and patients. Descriptive analyses were performed, comparing physician’s and patient’s responses by standard statistical analyses Results 144 physicians and 1302 patients responded to the surveys (overall mean age of 43 years (SD 9.5). 65% of physicians managed more than 200 patients and 80% had >5 years of experience. Most physicians (99%) were concerned about vaccines in IBD patients in their clinical practice, and 63% of them considered vaccines very important. Only 3.5% of physicians recommended live vaccines for their IBD patients with immunosuppressive treatments. One third of physicians did not recommend HPV vaccine. In spite of 69% of physicians recommending influenza vaccine during pregnancy, only 7.2% of pregnant patients indicated that they had received advice on influenza vaccination on their pregnancy (p Conclusion Deficiencies in knowledge regarding vaccination of IBD patients can be frequent. The perspective of physicians and patients is different, with physicians perceiving more recommendations related to vaccines than patients were recommended.

Background Extra-intestinal manifestations (EIM) are frequently reported in inflammatory bowel diseases (IBD). Although the efficacy of TNF inhibitors is well documented, data regarding the effect of vedolizumab (VDZ) and ustekinumab (UST) are limited. Theoretically, the advantage of VDZ, i.e. gut-selectivity, may reduce the efficacy on EIM while the systemic effect of UST may be of benefit. Therefore, we evaluated the differences in new onset and evolution of EIM during both treatments. Methods An international multicentric retrospective study was performed on IBD patients who started VDZ or UST between May 2010 and December 2020. EIM were assessed at baseline and during follow-up. Arthropathy was defined as joint inflammation (arthritis/sacroiliitis) and arthralgia as articular pain without confirmed inflammation. Skin EIM included erythema nodosum (EN), pyoderma gangrenosum (PG) and Sweet syndrome. Ocular EIM included (epi)scleritis and uveitis. Uni- and multivariate analyses were performed. Results In total 856 patients were included: 528 treated with VDZ and 328 with UST. At baseline, arthropathy was more prevalent in UST treated patients (12.2% vs 7.2%; p=0.037; Table 1). No differences in rates of new onset (Fig 1) or evolution of pre-existing arthropathies could be identified between VDZ and UST. In multivariate analyses new onset arthropathy was not associated with smoking, IBD type, sex nor studied biological. In 5 out of 48 (10.4%) VDZ patients and 2 of 46 (4.3%) UST patients with either pre-existing or new arthropathy, treatment was stopped due to articular disease (difference not significant). In contrast, new arthralgia onset within 1 year of follow-up was significantly associated with VDZ treatment (OR 2.1 (1.1–4.0); p=0.022; Fig 1). Arthralgia was the reason to stop treatment in 2 of 87 (2.3%) VDZ patients and never in UST patients. Beside joint EIM, 2 patients developed EN, 1 PG and 1 episcleritis during VDZ treatment. Under UST treatment 1 patient developed EN. No patients developed new Sweet syndrome, scleritis nor uveitis. Conclusion No differences in the rate of new arthropathy onset were observed between VDZ and UST. In contrast, VDZ treatment did increase the risk of new onset arthralgia.

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 Approximately one half of the patients with Crohn’s disease (CD) develop intestinal strictures during their lifetime. The effectiveness of currently approved drugs in fibrosis-predominant lesions is very limited. Our aim was to determine the effectiveness of anti-TNF therapy in CD complicated by symptomatic intestinal strictures in a real-world setting. Methods We included adult patients with symptomatic stricturing CD receiving their first-line anti-TNF therapy. Strictures were defined as constant luminal narrowing with pre-stenotic dilatation. We excluded those patients with previous anti-TNF exposure, surgery or endoscopic therapy of the stenosis. The effectiveness of the anti-TNF was defined as a composite outcome combining the persistence of the treatment and without dose or frequency intensification, with no new immunomodulators, surgery or endoscopic therapy during follow-up. A multivariate Cox regression was performed and the final multivariate model was determined using a backward procedure. Results A total of 262 patients from 32 sites were included (141 received infliximab and 121 adalimumab). The median number of stenosis per patient was 1 (range 1–9). The treatment was effective in 81% and 59% of patients after 6 and 12 months, respectively, while this outcome was fulfilled by 21% after a median of 40 months (IQR, 19–85). During follow-up, anti-TNF therapy required a dose or frequency adjustment in 39% of patients, 12% required a new immunomodulator or endoscopic therapy in 4%. The proportion of subjects requiring surgery was 15% and 21% after 1 and 2 years, respectively, with an overall rate of surgery of 32%. Infliximab was associated with a higher rate of surgery as compared with adalimumab (OR 1.78; 95% CI, 1,025-3,09). A shorter time since the diagnosis of CD or the stricture and the initiation of anti-TNF therapy was associated with a greater effectiveness at 6 and 12 months (HR 0.99 95% CI 0.99–1, p = 0.045; HR 0.99 95% CI 0.99–0.99, p = 0.015; HR 0.98 95% CI 0.96–0.99, p = 0.024; HR 0.99 95% CI 0.98–1.0, p = 0.046; respectively). In the survival analysis, younger age, lower albumin levels at baseline, strictures being located in the descending colon, concomitant use of mesalamine and the presence of ulcers or lymphadenopathy at the stricture were associated with lower effectiveness. The anti-TNF agent was discontinued in 131 patients (50%), and 88 subjects (34%) required a switch to a new biologic. Conclusion Anti-TNF agents are effective in approximately 20% of patients with CD complicated with symptomatic strictures. Early introduction of anti-TNF therapy improves the effectiveness in the short term in these patients. Some clinical and radiological predictors can identify patients with a lower probability of response.

Background Ulcerative colitis (UC) is a chronic, progressive and disabling disease with a complex pathology of unknown aetiology influenced by genetic, environmental and microbiota factors that lead to an immunological and inflammatory response in the colon. Janus Activated Kinase (JAK) family plays a key role in modulating the adaptive and innate inflammatory response. The JAK/STAT pathway involvement in UC has been demonstrated in both animal models and human studies. Thus, overexpressed JAK-3 has been detected in the intestine of patients with UC, suggesting a key role in their pathophysiology and the inhibition of TYK-2 in animal models resulted in an improvement of the disease, which would explain its implication in the inflammatory process. We hypothesise here that there could be an activation of JAK-3 and TYK-2 signalling pathways in UC patients. Thus, we aimed to detect the activation of both signalling pathways by means of western-blot studies in UC patient samples Methods A prospective, observational single-centre study was designed. Inclusion criteria were adult patients with endoscopic active UC (more than Mayo-0) confirmed in a programmed colonoscopy. All patients signed informed consent. Samples were obtained from overstock of routine biopsies in the more severe segment affected of the large bowel. Tissues were homogenised and processed in order to obtain cell lysates by employing RIPA buffer and ultrasounds. The degree of activation of the JAK-3 and TYK-2 pathways was measured by detecting the phosphorylation of both targets as well as of STAT1, STAT3, STAT4, STAT5 and STAT6 through western blot by employing specific antibodies for total and phosphorylated proteins. Results 19 UC patients were consecutively included. Mean age was 46 years old. 53% were female, 47% were extensive colitis (E3) and 53% left-side colitis (E2). Regarding endoscopic activity, 26% had Mayo-1, 53% Mayo-2, and 21% Mayo-3. Immunoreactive bands for both phosphorylated JAK-3 and TYK-2 were detected in the biopsies from UC patients, evidencing that colonic inflammation leads to an activation of both targets. The study of STATs phosphorylation showed immunoreactive bands for phosphorylated forms of STAT1, STAT3, STAT4, STAT5 and STAT6 confirming the activation of both signalling-pathways in these patients (Figure 1). Conclusion The developed translational workflows involving basic/clinical research confirm the activation of both JAK-3 and TYK-2-dependent signalling pathways in UC patients, validating both kinases as targets for treating UC. The developed methodology allows studying the target engagement for future JAK-3/ TYK-2 inhibitors employed in clinical trials.

Background There is no evidence about the time that it is reasonable to wait until starting Vedolizumab (VDZ) or Ustekinumab (UST) in case of loss of response to anti-TNF therapy. The aim of our study was to evaluate whether the time between the change from any anti-TNF drug to VDZ or UST had an influence on the risk of treatment failure and the rate of adverse events or severe infections. Methods A retrospective, observational single-centre study was designed. Inclusion criteria were all adult patients with moderate-to-severe IBD who started treatment with VDZ or UST due to loss of response to anti-TNF (Infliximab or Adalimumab). Exclusion criteria were patients who had received treatment for different indications such as prevention of recurrence or extra-intestinal manifestations. Patients that changed directly from VDZ to UST or from UST to VDZ were also excluded. We defined two groups of periods based on the interval of time between the last dose of anti-TNF and the first dose of VDZ or UST: Group A: early (≤30 days), Group B: late (31–60 days). Patients that had a waiting time of over 60 days were also excluded. Treatment failure after the initiation of VDZ or UST was defined as the need for dose intensification, surgical resection, therapy removal for ineffectiveness or adverse reaction. The existence of infections was also evaluated. Results are shown as percentages, median, range and Hazard Ratio (CI 95%). Fisher test and Cox Regression analysis were also performed. Results 46 patients (45.6% CD) were consecutively included (mean age 47.6 years). 17 had initially been treated with Infliximab and 29 with Adalimumab. Thirty patients were changed to VDZ and 16 to UST. Twenty-three patients were included in Group A and 23 in Group B. Treatment failure was observed in 20 patients: 9/23 in group A and 11/23 in group B with a mean follow-up of 323 days (range 152–432). The duration of the interval of time between stopping anti-TNF and starting VDZ or UST was not associated with increased risk of treatment failure (p = 0.25) with a median of time until loss of response of 252 days (range 98–432 days) in Group A and 168 days (range 131–418 days) in group B (Figure 1). No differences were found between patients with CD or UC (p = 0.23) and no differences were found in starting with VDZ or UST. There was 1 adverse event that forced a stopping of treatment in group A. No infections that required hospitalisation were observed. Conclusion The interval of time between anti-TNF and VDZ or UST had no influence on the rates of treatment failure, adverse events or infections in our cohort.

Background: Predicting relapse in Crohn’s disease (CD) patients by measuring non-invasive biomarkers could allow for early changes of treatment. Data are scarce regarding the usefulness of monitoring with calprotectin to predict relapse. The aim of the study was to evaluate the predictive value of a rapid test of fecal calprotectin to predict for flares in CD patients under maintenance treatment with adalimumab (ADA). Methods: A prospective, observationalcohort study was designed. Inclusion criteria were CD patients in clinical remission for at least six months under a continuous standard dose of 40mg/eow ADA therapy. Fresh faecal calprotectin was measured using a rapid test (Quantum blue®) on the day of the first ADA injection. Quantum blue ®is a rapid test for measuring calprotectin in less than half an hour. Clinical examination was performed during the following 4 months. Relapse was defined as a Harvey Bradshaw score >4. Results are shown as mean±SD and compared by the U-Mann Whitney test. ROC analysis was performed and the diagnostic accuracy was calculated. Results: Thirty patients were included (mean age 40 years, 56.7% female). After the four months follow-up, twentyone (70.0%) patients remained in clinical remission and nine (30.0%) have had a relapse. Fecal calprotectin concentration at inclusion was significantly higher in those patients who relapsed during the follow-up (803±514mg/g) than in those who maintained in remission (95±104mg/g) (p < 0.005). The optimal cut-off of fecal calprotectin to predict remission was 204mg/g according to the ROC analysis. The area under the ROC curve was 0.97 (p < 0.005). Sensitivity, specificity, positive and negative predictive value of fecal calprotectin to predict relapse were 100%, 85.7%, 74.1% and 100%, respectively. Levels of calprotectin were correlated with levels of C-reactive protein (r = 0.51, P< 0.005). After multiple linear regression, we observed that if we made adjustments with other relevant sociodemographic and clinical variables, calprotectin and older age were the most important risk factors for the presence of relapse. Conclusions: In CD patients under ADA maintenance therapy, fecal calprotectin levels allow predicting relapse over the following months with a high accuracy. Low fecal calprotectin levels exclude relapse within at least the following four months, whereas high levels are associated with relapse in three out of each four patients.

medical notes and the internal electronic results system to assess these two conditions. Results: The prevalence of IBD and PD within the UK population is said to be 225/100,000 (UC 150/100,000 + CrD 75/100,000) and 140/100,000, respectively. The L&D catchment area covers 330,000 and so one would have expected approximately 742 IBD and 462 PD patients, respectively. The databases had 2783 IBD patients (median age = 79) and 350 PD patients (median age = 51) listed. Probability analysis would suggest we should expected 1 patient to have concomitant PD and IBD, however, we found 6 subjects with the concomitant conditions. This translates into 0.2% of IBD patients having PD and 1.72% of PD patients having IBD.