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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 Telemedicine is not consistently superior to standard care in the management of inflammatory bowel disease (IBD). Non-inferiority is an acceptable outcome if telemedicine improves the efficacy and efficiency of care. Owing to the positive results of the TECCU app (Telemonitoring of Crohn’s Disease [CD] and Ulcerative Colitis [Au]) in a pilot trial1, we aimed to evaluate the time in remission and quality of life (QoL) of IBD patients controlled by telemonitoring (G_TECCU), compared to standard care (G_Control) after 12 weeks. 1Del Hoyo J et al. J Med Internet Res. 2018;20(11):e11602. Methods A 2-arm randomized multicenter study with a non-inferiority design was performed in 29 IBD centers in Spain. Adult IBD patients who initiated therapy with immunosuppressant or biological agents for disease activity were included. Exclusion criteria were: patients with ileorectal/ileo-pouch anal anastomosis, stoma, active perianal disease, no Internet access. Time in remission was evaluated with Harvey-Bradshaw/Walmsley indexes (according to CD]/UC, respectively), fecal calprotectin (FC) and reactive C protein (RCP). QoL was assessed with IBDQ-9, medication adherence with Morisky-Green index and patient satisfaction with a questionnaire derived from CSQ-8. Results We included 157 patients, and 126 were analyzed after 12 weeks of follow-up. The demographic and clinical variables are listed in Table 1. The time in remission was not inferior in patients who used the TECCU app (mean 4.2 weeks [SD 3.8]) compared with patients who received standard care (mean 4.2 weeks [SD 3.2]; difference 0.03 [95%CI -1.21 to 1.27]; p=0.017) (Figure 1). In patients with UC, disease activity improved significantly in both TECCU (mean SCCAI improvement -3.60 [SD 3.25]; p= 0.001) and standard care groups (-3.89 [SD 4.56]; p=0.001;). In patients with CD, clinical activity also improved significantly in both groups (mean Harvey-Bradshaw improvement -1.65 [SD 2.51]; p=0.001 in TECCU; -2.24 [SD 4.15]; p=0.001 in standard care group). Similarly, FC and CRP values improved significantly in both groups (Figure 2). Considering QoL, the IBDQ-9 score improved significantly in TECCU (mean 11.29 [SD15.8]; p Conclusion In IBD patients who initiate biological agents or immunomodulators, TECCU app is not inferior to standard care to maintain remission in the short-term. Telemonitoring with TECCU app associated a higher improvement in medication adherence and an increase in QoL. Long-term results are needed to confirm it.

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

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

Background 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 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 Crohn′s disease (CD) is a progressive inflammatory bowel disease that can lead to complications such as strictures or penetrating disease, and ultimately surgery, representing a complex clinical challenge in the care of patients. We aimed to evaluate the influence of CD phenotype in the retention rate of ustekinumab in the Sustain study. Methods Retrospective, multicentre study (>60 sites) including patients with active CD [(Harvey-Bradshaw (HBI)>4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission. Disease characteristics were collected (date of diagnosis; location; behaviour: inflammatory, stenosing or penetrating; presence of perianal disease or extraintestinal manifestations; previous surgeries, etc.). The retention rates in patients on ustekinumab depending of their disease phenotype were evaluated by descriptive analysis and Kaplan-Meier survival curves. Survival curves were compared using the log-rank test. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring. Results 463 CD patients were included (Table 1). 87 patients (18.6%) had penetrating CD in our cohort. The probability of maintaining UST treatment was 91% at 6, 83% at 12, 76% at 18 and 73% at 24 months. Similar retention rates were observed in patients with inflammatory (77.6%), stricturing (76.4%) and penetrating (79%) disease behaviour (p>0.05). Figure 1. Conclusion Ustekinumab has shown to be equally effective in the treatment of inflammatory, stricturing and penetrating CD phenotype in Sustain, the largest study evaluating its use in CD in clinical practice, having the longest follow-up period reported to date.

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 Ileocolonoscopy is the gold standard to evaluate post-operative recurrence (POR) in Crohn's disease (CD) patients. Rutgeerts endoscopic score remains the gold standard in the evaluation of post-operative recurrence in CD. Intestinal ultrasound (IUS) is proposed as a non-invasive alternative to ileocolonoscopy for the diagnosis of POR, with a sensitivity of 94% and specificity of 84%. There are several IUS scores that evaluate CD disease activity such as SUS-CD (validated), IBUS-SAS and Simple US Score, which have not yet been studied in the diagnosis of POR. The aim of this study is to assess whether these ultrasound scores correlate with endoscopy in the diagnosis of PR. Methods A retrospective study was performed. Patients with CD who had undergone ileocecal resection, with both an ileocolonoscopy and intestinal ultrasound performed for the detection of POR were included. The time between tests was less than 6 months and there was no therapeutic change between tests. Endoscopic POR was evaluated with Rutgeers score (RS), considering POR RS ≥i2b. In IUS, were used: Simple US Score, SUS-CD and IBUS-SAS. Results Forty-five patients were included (female 48,89%, male 51,11%). The Montreal classification was: L1 n=22 (48,89%), L2=1 (2,22%), L3 n=22 (48,89%), B1 n=3 (6,67%), B2 24 (54,4%) and B3 n=18 (40%). 24 patients (53%) had no endoscopic POR, 6 (6%) had RS i2b and 15 (33.33%) had severe POR. The mean wall thickness measured by IUS was 4.39 mm (SD +/- 1.92) and 26 patients (57.77%) had hyperemia (Limberg score >1). The mean values for IUS scores were: Simple US Score 5.79 (SD +/- 2.81), SUS-CD 2.35 (SD +/- 1.62) and IBUS-SAS 34.04 (SD +/- 24.21). For the Simple US Score an area under the ROC curve (AUC) of 80.65% (95% CI 67.7 - 93.6) was obtained, with a score ≥5.4. The sensitivity (S) was 95.24% and specificity (E) 66.67%. IBUS-SAS presented an AUC of 87% (95% CI 76.98 - 97.02), a result ≥28 granted a S 90.48% and E 70.83%. The SUS-CD index had an AUC of 79% (95% CI 76.98 - 97.92), a result ≥3 presented S 90.48% and E 62.5%. Conclusion In our experience, IUS scores (IBUS-SAS, SUS-CD and Simple US Score) show a high sensitivity in the diagnosis of POR.

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 Fecal calprotectin (FC) has become a fundamental tool in the non-invasive monitorization of activity in patients with inflammatory bowel diseases (IBD). However, there is still debate over the choice of the optimal cut-off point for the different clinical settings. The aim of this study is to analyze whether the presence of pseudopolyps and their characteristics have an impact on the value of FC and should therefore be taken into account when deciding the optimal cutoff values. Methods A single-centered, retrospective analysis including data from patients with colonic Crohn′s disease or Ulcerative colitis who underwent colonoscopy for dysplasia screening at our center between 2018 and 2019. Patients that did not have a FC registered within 8 months from to the colonoscopy, or that did not maintain clinical remission between the colonoscopy and the measurement of the FC, were excluded. Patients that had activity in the colonoscopy (Mayo endoscopic score >0, SESCD >0) were also excluded. Results 73 patients were included. 26 (35.6%) of them had pseudopolyps in the colonoscopy. The median value of the FC was significantly different in patients with pseudopolyps (110.1 µg/g, CI 95% [48.6–171.5]) compared to those without them (52.5 µg/g, CI 95% [29.9–75.1]). In 11 (42.3%) of the patients with pseudopolyps, biopsies were taken, observing histological activity in 3 of them (27.3%) and no inflammatory activity in the other 8 (72.7%). We found that FC was higher in patients with inflammatory polyps (119.0 µg/g) in comparison to those without histological activity in their pseudopolyps (96.9 µg/g); however, these results were not statistically significant. The location of the pseudopolyps had no influence over the FC in our study. In addition, no correlation was found between the presence of polyps or diverticula and FC. Conclusion In our study, the presence of pseudopolyps is associated with significantly higher levels of FC. Moreover, our results suggest a tendency towards higher FC in patients who had active colitis in the histological samples of their pseudopolyps.

Background Whether to use biologic treatment for inflammatory bowel disease as monotherapy or in combination with immunosuppressives has been a matter of debate in the last years. We aimed to evaluate if immunosuppressants influenced the retention rate of ustekinumab in Sustain, the largest study evaluating its use in clinical practice, having the longest follow-up period reported to date. Methods Retrospective, multicentre study (>60 sites) including patients with active Crohn′s Disease (CD) [(Harvey-Bradshaw (HBI)>4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Data on concomitant immunomodulatory therapy (if any) with azathioprine, mercaptopurine, methotrexate or others at the start of ustekinumab treatment and during follow-up were documented. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission. The retention rate in patients on ustekinumab receiving or not immunosuppressive treatment was evaluated by descriptive analysis and Kaplan-Meier survival curves. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring. Results 463 CD patients were included. Prior CD treatments to ustekinumab were collected: the majority of patients received steroids, immunosuppressants and biologics. Figure 1 shows the percentage of patients on treatment with each type of drug and whether or not they continued to receive it when they started ustekinumab, in the case of steroids and immunosuppressants. Reasons for discontinuation of previous immunosuppressive treatments for CD were as follows: failure (37.5%), sustained remission (5.8%), adverse event (47.6%), medical decision (4%), other reasons (5.1%). During ustekinumab treatment, 163 patients (35.2%) received immunosuppressants (listed in figure 2). Sixty-six (14.3%) patients had their immunosuppressant withdrawn during treatment. Retention was observed in 77.9% of patients with concomitant immunosuppressive therapy versus 76.3% of patients without. There weren′t statistically significant differences between the two populations (p=0.712). Figure 3. The patient-year discontinuation rate for patients who didn′t receive concomitant immunosuppressants was 17.5 versus 18.9 in those who received them. Conclusion No effectiveness differences were seen by adding immunosuppressants to ustekinumab, reinforcing the low immunogenic profile of this drug and reducing the risk of additional side effects and toxicity.

Background Chronic inflammatory diseases, including the Inflammatory Bowel Disease (IBD), show an increased risk in the development of atherosclerotic cardiovascular disease and coronary microvascular dysfunction at an early age. AntiTNF α have proven to be effective in reducing the cardiovascular risk in these malaises, nevertheless due to their mechanism of action, we cannot determine whether such efficacy is due to an adequate inflammation control or due to the specific cytokine blockade, which plays an important role in both the inflammation and the atherogenic process. Taking this into account, our hypothesis assesses whether using other anti-inflammatory therapies, such as Ustekinumab and Vedolizumab, would achieve a decrease in cardiovascular risk. Methods In this observational and retrospective study, we collected cardiovascular risk factors(CVRFs) in 46 patients, immediately before starting Ustekinumab or Vedolizumab and a year after, taking into account if patients were in clinical remission or not. The CVRFs included were: body mass index (BMI), arterial hypertension, triglycerides values, lipid profile, albumin and C-reactive protein. Results 46 patients were included, 33(71.74%) with Crohn and 13(28.26%) with Ulcerative Colitis. Of the total number of patients 25(54.35%) were treated with Ustekinumab and 21(45.65%) with Vedolizumab. During the follow-up, only one patient(0.02%) presented a new cardiovascular event. Paired student’s t-test were used for data analysis in both treatment groups, comparing the values of the different CVRFs at the baseline and after one year of treatment. When comparing these values according to clinical remission at one year, no statistically significant differences were observed for any of them. BMI and weight values were |24.49(DE 4.58) vs 24.93(DE 4.74) p=0,71| and |70.76kg(DE 13.86) vs 71.38kg(DE 13.33) p=0,85| respectively. As for hypertension, no relevant changes were observed, representing 15.22% of the population at the beginning and 17.39% after one year of treatment. The differences observed in blood glucose values were|86.23(81.87–90.6)mg/dL vs 89.87mg/dL(84.72–95.01) p=0,27|. Regarding the lipid profile, the total cholesterol values were 158.58mg/dL(DE 36.5) and 168.69mg/dL(DE 32.72) p=0.18. HDL at the beginning 44.67mg/dL(DE 11.69) and after one year 47.43mg/dL(DE 10.19) p=0.28 and triglycerides values of 126.65mg/dL(DE 56.38) and 133.5mg/dL(DE 60.95) p=0,61. Albumin levels|4.08g/dL(DE 0.39) vs 4.27g/dL(DE 0.27)|did show significant differences (p=0,01). Conclusion Patients treated with Vedolizumab or Ustekinumab do not present a significative reduction in the cardiovascular risk after one year regardless of clinical remission.

Background Clinical trials and real-life studies with Ustekinumab in Crohn’s disease show its good efficacy and safety profile. However, there are hardly any data on elderly patients, who are excluded from these clinical trials. Our aim is to evaluate these variables in real-life practice. Methods Retrospective analysis of patients from the prospectively maintained ENEIDA registry treated with Ustekinumab for Crohn’s disease. Elderly patients were selected as those over 60 years old at the start of treatment. They were compared with 2 randomised controls from the same centre, aged less than 60 years, matched for smoking habit. The degree of comorbidity was assessed using the Charlson’s index. Clinical and biochemical activity and effectiveness were defined based on Harvey-Bradshaw index and calprotectin and CRP levels at weeks 16, 32 and 54, when available. Results A total of 648 patients were analysed, 212 elderly (mean age 67 [63.6;72.8] years) and 436 young (mean age 41.6 [32.6;50.0] years). No differences were observed between both groups in baseline variables except for the degree of comorbidity, higher in elderly patients (1.00 [0.00;2.00] vs 0.00 [0.00;0.00], p Clinical response rate was similar in both groups at week 16 (70.5% vs 76.6%, p=0.199), week 32 (67.6% vs 70.2% p=0.104) and week 54 (74% vs 74.9%, p=0.326). Steroid-free remission and biochemical response also showed no differences throughout follow-up. The rate of adverse effects was similar in both groups (14.2% vs 11.2%, p=0.350) except for the occurrence of de novo neoplasms, which was higher in the elderly group (0.69% vs 4.25%, p=0.003). The rate of severe infections (7.08 vs 7.34, p=1.000), the need for surgery (16.5% vs 20.0%, p=0.345) and the need for hospital admission (21.7% vs 19.0%, p=0.489) did not differ. Persistence of UST treatment was similar in both groups (log Rank test p=0.91). Conclusion Ustekinumab achieved clinical response in almost three-quarters of elderly patients, similar to the younger population, with no increase in the rate of infections or other adverse effects, with the exception of de novo neoplasms.

Background Thiopurines (TP) are widely used in monotherapy in patients with ulcerative colitis (UC), mainly for the maintenance of remission in case of corticodependence or corticoresistance after cyclosporine use. However, these are drugs with significant side effects, especially in the long term. The optimal duration of treatment with TP remains unknown, so it is important to determine the risk factors for relapse in order to identify the group of patients in which treatment can be withdrawn. Methods A retrospective study was performed. Patients with UC in remission, in maintenance treatment with TP, who had discontinued the drug due to either maintained remission or the onset of adverse effects were included. Results 26 patients were included, 1 with proctitis, 9 with left colitis and 16 with pancolitis. 24 (92.31%) were treated with azathioprine and 2 (7.69%) with mercaptopurine. The mean treatment time with TP was 68.09 months (standard deviation 56.65). 11 patients (42.31%) discontinued TP due to adverse effects and the remaining patients (57.69%) discontinued it by medical decision because they were in prolonged remission. After withdrawal of TP, 92.34% of patients continued treatment with mesalazine and the remaining 7.69% without concomitant treatment. During follow-up, 10 patients (38.4%) relapsed and 16 patients (61.53%) had no relapse until the end of follow-up. The mean time from TP withdrawal to the onset of relapse was 69.15 months (standard deviation 52.53). Of the 10 patients who presented a flare, 5 (50%) were controlled by optimizing the dose of mesalazine, 4 (40%) required the addition of oral corticosteroids and 1 (10%) required biologics. No significant differences were found when comparing the time to relapse if the reason for discontinuation of TP was having had an adverse effect (65.05 months) or maintained remission (79.79 months) (p=0.42). No statistically significant differences were found in time to relapse when comparing time on TP treatment, presence of concomitant treatment with mesalazine or active smoking. Conclusion One third of patients relapsed after TP withdrawal. Discontinuation of TP in patients with UC in remission should be individualized according to the patient’s risk factors, the indication and the duration of treatment.

Background Colonic neoplastic risk is increased in long-standing colitis. Chromoendoscopy (CE) is the recommended screening method. Narrow band imaging (NBI) is potentially a more convenient alternative. Few studies have explored the diagnostic yield of second generation NBI (Olympus 190 series) versus chromoendoscopy. Methods NBICromo (NCT04403997) is an ongoing prospective randomized controlled trial in which patients with clinical indication for CE (>8 years of disease, left-side or extensive colitis, colonic Crohn′s disease with >2 colonic segments affected or associated primary esclerosing cholangitis) are randomized on 1:1 ratio to CE with methylene blue 0,1% or NBI. All procedures are done with Olympus HQ190 endoscopes by endoscopists with experience in IBD. Biopsies are taken from all visible lesions. Primary objective is to compare the total number of neoplastic lesions detected in each group. Secondary objectives are to compare the procedure time, the number of biopsies taken,and the accuracy of optical characterization of the lesions. The study has been approved by the Hospital Ethics Committee and patient informed consents were obtained. Estimated sample size for the study is 175 patients, and recruitment is currently ongoing. An interim analysis was conducted with the first 75 randomized patients to exclude futility due to slowed recruitment caused by covid-19 pandemic. Results 75 patients were randomized, 34 to CE and 41 to NBI. 10 patients were excluded due to presence of inflammation or poor bowel preparation in the colonoscopy. 65 patients were analyzed per protocol, 31 in the CE arm and 34 in the NBI arm. Mean age was 57±13 years, 46.15% were male and 53.85% female. Mean disease duration was 17.1 ± 8.3 years. No significant differences were found between groups in basal characteristics. 123 lesions were detected. 77 with CE and 46 with NBI, of these 34 (27,6%) were neoplastic (14 neoplastic lesions were found in NBI group and 19 in CE group p=0.1. Neoplastic lesions were found in 13 patients in CE group (41,9%) and 7 patients with NBI (20,5%) p=0.06. Total withdrawal time (including staining and/or therapeutics) was significantly shorter in the NBI group (17.6 ±9.8 vs 30.5 ± 16.5 min p AE were 1 mild post resection bleeding and 1 mild fever, both in the CE group p=0.07. Conclusion In this interim analysis there are no significant differences in dysplasia detection between CE and NBI, although more sample size is needed. NBI could be a more convenient alternative to CE, with significant shorter and more simple procedures. The ongoing clinical trial will be completed.

Resumen La presencia de actividad de la enfermedad inflamatoria intestinal durante la gestacion puede afectar el curso del embarazo. Por ello el mejor consejo es que la concepcion se produzca cuando la enfermedad este en remision. Ante un brote de actividad durante el embarazo, es necesario iniciar tratamiento lo mas rapido posible para inducir la remision y asi evitar cualquier complicacion. Presentamos el caso de una mujer, que estando en tratamiento con adalimumab queda embarazada, y que presenta un brote de la enfermedad que precisa de intensificacion del tratamiento hasta finalizar la gestacion. El final del embarazo asi como el parto se desarrollan sin complicaciones maternas ni fetales.

Background The combination of anti-TNF drugs with thiopurinic (TPH) drugs in the treatment of IBD, has shown greater clinical efficacy, serum drug levels in therapeutic range in a higher proportion of patients, and less antibody formation, than monotherapy with anti-TNF. However, the dose of the TPH drug in combined treatments has not been clearly established. Some authors consider that this dose could be lower than that used in monotherapy (2.5 mg/kg/day). Methods A retrospective study was performed, selecting all patients with the diagnosis of IBD in follow-up at the Hospital La Paz, from 2006 to 2018, who were on combined treatment with azathioprine (AZA) and Anti-TNF. 91 patients were recruited for treatment with infliximab (IF) and 52 for treatment with adalimumab (AD). Two groups were established for both IF and AD, one with the standard dose (2–2.5 mg/kg) and one with a lower dose (less than 2 mg/kg). The main objectives are to evaluate the clinical and pharmacokinetic response: through the measurement of the levels of the biological drug and the formation of anti-drug antibodies (ADA). As secondary variables, PCR and faecal calprotectin are determined Results In the AD group, there are no statistically significant differences in remission rates, response without remission, or failure depending on the dose of TPH (adequate or low). There are no differences between PCR and calproctectin levels among patients with optimal doses of TPH and low doses. The last determinations of mean AD levels were not significantly different between groups. No ADA formation was detected. In the IF group, there is no statistically significant difference in remission, response or failure rates depending on the dose of TPH. There are no differences between the levels of PCR and faecal calprotectin, nor in the formation of ADA; nor in the last two determinations of mean IF levels among patients with optimal doses of thiopurines vs. lower doses. If we consider pharmacokinetic failure (infliximab levels < 1000 μg/ml and/or ADA), there were also no statistically significant differences. Conclusion Consistent with the findings of other studies, there are no differences in the pharmacokinetic characteristics or in the responses of patients depending on the dose of azathioprine. The use of a lower dose of AZA can provide a better tolerance of the drug, a better safety profile, and lower economic cost.

Background The ‘treat to target’ strategy for managing patients with Crohn’s disease (CD) requires simple, reliable and non-invasive monitoring tools. Bowel ultrasound is an emerging technology that could be useful in this field. The aim of our study is to determine whether bowel ultrasound is a useful tool to assess activity in CD and if its results correlate with long-term evolution of the disease. Methods Patients who had a bowel ultrasound for clinical practice between February 2013 and October 2018 in our centre were retrospectively included. Evolution of patients was assessed at follow-up based on the presence of echographic signs of activity and therapeutic changes solely based on echographic features. Results 277 CD patients were included, of which 51% (142 patients) are women with a mean age at diagnosis of CD 35.3 years old (18.7 SD). The median follow-up time was 24 months (range 5–73 months). Among patients included, echographic signs of inflammatory activity were identified in 166 patients (60%). Out of these, 116 patients (70%) received treatment step-up based on the results of ultrasound. It was observed that out of the 161 patients (58%) in which of the attending physician did not modify treatment after performing ultrasound, only 43 had activity on ultrasound (26.7%). Also among patients whose treatment was scaled, 100% had echographic activity. These differences reached statistical significance (p < 0.0001). Among patients with echographic activity, disease evolution was worse than in those without activity, presenting less time to the next disease flare. Thus median disease-free survival (without flares) after performing ultrasound was 18 months when ultrasonographic activity identified (although in most patients (70%) treatment was scaled) vs. 47 months in patients without ultrasound activity, with statistically significant differences (p < 0.0001). Conclusion Intestinal ultrasound is a technique capable of detecting inflammatory activity in patients with Crohn’s disease and the presence of ultrasound activity is a risk factor for a subsequent activity flare and/or clinical relapse.

Resumen Hasta un 30% de los pacientes con enfermedad de Crohn son refractarios a corticoides, precisando la introduccion de tratamientos inmunosupresores o biologicos o cirugia. Debemos realizar un adecuado diagnostico diferencial conociendo que multiples infecciones pueden mimetizar la clinica de la enfermedad inflamatoria intestinal y su diagnostico no siempre es sencillo. Se presenta un caso de un paciente con una enfermedad de Crohn ileocolica, sin factores de riesgo epidemiologico, refractario a tratamiento corticoideo por una sobreinfeccion por Entamoeba histolytica.

Background:Musculoskeletal manifestations (MEM) are frequent extraintestinal symptoms in patients suffering from inflammatory bowel disease (IBD), affecting up to 40% of them. Tumor necrosis factor inhibitors (TNFi) are effective in both IBD and IBD-related spondylarthritis (SpA). Additionally, vedolizumab (VDZ), an α4β7 integrin inhibitor with selective action on intestinal tissue, has been recently proposed as 1st line treatment on TNFi refractory IBD. The effectiveness of VDZ in MEM has not been properly evaluated but even exacerbation of previously diagnosed SpA has been described.Objectives:The main objective is to analyse the occurrence of articular exacerbations in patients with IBD-related SpA treated with VDZ. The secondary objective is to analyse the new-onset MEM in IBD patients treated with VDZ.Methods:Descriptive study of a retrospective cohort of every adult with IBD (Crohn’s disease -CD- and ulcerative colitis -UC-) patients starting treatment with VDZ in a tertiary hospital. All data were collected as a collaboration between the Rheumatology and Gastroenterology Departments, through revision of the clinical history and databases from both departments. In patients previously diagnosed of SpA exacerbation was assessed, defined as a clinical worsening causing a treatment modification. The patients with new-onset MEM were classified as: i) nonspecific arthralgia (NsA), not suggestive of SpA; and ii) SpA according to ASAS criteria. A statistical analysis was performed using frequency chartsResults:A total of 61 patients were included, 55.7% women and with an mean (SD) age of 50 (17) years. The proportion of UC and CD was similar (49% and 51%, respectively). Among the patients studied, 12 (19.7%) had a diagnosis of IBD-related SpA and 3 (25%) of them suffered articular exacerbation of SpA within 3,5 and 6 months of treatment. On the other hand, 9 (14.7%) patients showed new-onset MEM, 3 (33%) of them showed symptoms and clinical and/or radiological findings compatible with axial SpA. In 2 of the cases a treatment with a cDMARD was used and the other one required a combination therapy between iTNF and VDZ. The remaining 6 (67%) patients were classified as NsA and inflammatory arthritis was discarded. Table 1 shows the demographic and clinical characteristics of patients included in the analysis.Table 1.Demographic, clinical characteristics and symptoms onset in patients included in the study.Total (n=61)Diagnosed SpA (n=12New-Onset MEM (n=9)Stable (n=9)Exacerbation (n=3New-onset SpA (n=3)NsA (n=6)Age (years), mean ± SD50 ± 1755 ± 1950 ± 7.538 ± 1350 ± 14Gener (female), n (%)34 (55.7%)6 (66.7%)3 (100%)1 (33.3%)3 (50%)BMI (Kg/m2), mean ± SD24.7 ± 4.327.5 ± 5.528.3 ± 3.930.2 ± 0.524.3 ± 4.6Smoking habit (smokers), n (%)11 (18%)1 (11.1%)0 (0%)2 (66.7%)0 (0%)CD diagnosis, n (%)31 (50.8%)2 (22.2%)1 (33.3%)3 (100%)2 (33.3%)UC diagnosis, n (%)30 (49.2%)7 (77.8%)2 (66.7%)0 (0%)4 (66.7%)IBD follow-up, (years) mean ± SD11 ± 9.610.6 ± 102 (1-29) *12 ± 6.89.8 ± 4.6bDMARD naïve, n (%)7 (11.5%)2 (22.2%)0 (0%)0 (0%)0 (0%)*shown as median (range).Conclusion:Switching TNFi treatment to VDZ in patients with IBD-related SpA was found to be associated with articular exacerbation of SpA in 1 out of 4 patients within the first 5 months. New-onset MEM is also observed in up to 15% of patients with IBD treated with VDZ. A multidisciplinary assessment of these patients is necessary in order to achieve a proper management of their diseases.Disclosure of Interests:Pablo Rodríguez-Merlos: None declared, MARIA ANGELES RUIZ- RAMIREZ: None declared, Chamaida Plasencia: None declared, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, Cristina Suarez-Ferrer: None declared, Eduardo Martin-Arranz: None declared, Maria Dolores Martín Arranz: None declared, Diana Peiteado: None declared, Gemma Bonilla: None declared, María Sánchez Azofra: None declared, Joaquín Poza Cordón: None declared, Karen Nathalie Franco Gomez: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz

Background After the appearance of new biologics are more treatment options for first and second-line individualising according to the characteristics of each patient. The efficacy of a second anti-TNF is lower than the initial treatment so a more efficient strategy could change the therapeutic target. Methods We included patients with an established diagnosis of Crohn’s disease who were on second-line biological treatment (ustekinumab or anti-TNF) after failure of a first anti-TNF (adalimumab or infliximab) treatment. Only patients in whom the indication was the ‘induction of remission of inflammatory activity’ so those patients in whom the indication was different from the intestinal activity (intestinal manifestations, perianal disease etc.) were selected were not considered valid for analysis. Patients who had undergone intestinal resection alone were included in the study if the indication of second-line biologic treatment was already established and no recurrence prophylaxis thereof. Results A total of 56 patients with an established diagnosis of Crohn’s disease stable tracking unit EII La Paz Hospital who were treated with second-line ustekinumab (21 patients, 37.5%) or anti-TNF (35 patients were included, 62.5%) for remission induction. Baseline characteristics of patients and their IBD are summarised in Table 1. The duration of biological treatment at the time of analysis was 1.48 years (SD: 1.2) for ustekinumab group and 3.55 years (SD 3.3) for the anti-TNF group. Ustekinumab group in 16/21 (76.2%) achieved clinical remission, 3/21 (14.3%) had no response while achieving remission (note that in one patient occurred exitus otherwise cause adenocarcinoma páncreas- unable to properly assess drug response), 2/21 patients (9.5%) did not answer. In the group of anti-TNF, 15/35 patients (42.8%) achieved clinical remission, 12/35 patients (34.3%) had response without remission, 8/35 patients (22.9%) No response. These differences between groups reached statistical significance (p = 0.015). Among patients who achieved a response / clinical remission included those wherein assessed by endoscopy identifying intestinal activity no statistically significant differences between groups vs. anti-TNF ustekinumab both SESCD (average 2 vs. 6.3 p = 0, 39) to the Ruttgerts in (mean 2.5 vs. 2, p = 0.67) postsurgical stage. Regarding the response/biological remission found no significant differences in CRP between ustekinumab and anti-TNF (4.55 vs. 5.79, p = 0.68) or with fecal calprotectin (276.25 vs. 268.82, p = 0.94). Conclusion In our experience, the second-line treatment with ustekinumab after the failure of a first anti-TNF has better remission rates and response to treatment with a second anti-TNF.

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.

Infliximab (IFX) is a valid treatment for Crohn’s disease (CD), but a relevant percentage of patients do not benefit from this therapy. In the Japanese population, the response to IFX was associated with markers in the TNF receptor superfamily 1A ( TNFRSF1A ) and 1B ( TNFRSF1B ) genes. We aimed to replicate the association previously described in the Japanese population and to ascertain the role of TNF receptors as modulators of the response to IFX. We studied 297 white Spanish CD patients with a known response to IFX: 238 responders and 59 primary nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed: rs767455 in TNFRSF1A and rs1061622 , rs1061624 , and rs3397 in TNFRSF1B . Comparisons between groups were performed with chi-square tests or the Fisher’s exact test. Different features (sex, age, disease duration, smoking among others) were evaluated as possible confounding factors. No significant association was found between the studied TNFRSF1A polymorphisms and response to IFX. In the TNFRSF1B gene, the haplotype rs1061624_A-rs3397_T was significantly increased in nonresponders: p = 0.015, OR = 1.78, 95% CI 1.09–2.90; and an increased frequency of rs1061622_G carriers was observed in patients with remission: p = 0.033 vs nonresponders and p = 0.023 vs patients with a partial response. Our results support a role of TNFRSF1B gene variants in the response to IFX in CD patients.

Resumen La purpura trombocitopenica idiopatica es una manifestacion extraintestinal poco frecuente de la enfermedad inflamatoria intestinal, y sobre todo es rara en la enfermedad de Crohn, donde presenta ciertas peculiaridades respecto a su clinica habitual, de tal manera que ocurre con mas frecuencia cuando la enfermedad de Crohn es de predominio colonico, suele aparecer un tiempo despues del diagnostico de esta y, ademas, complica el curso clinico de ambas enfermedades. En este trabajo se presenta un caso de enfermedad de Crohn asociada a purpura trombocitopenica idiopatica, en una mujer de 14 anos en la que la purpura trombocitopenica idiopatica se inicio de forma simultanea a la enfermedad de Crohn, con mala evolucion clinica y resistencia a los tratamientos habituales de ambas enfermedades.

Background Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. Aim To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. Methods We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. Results In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). Conclusion These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers.

Globular amyloidosis is a very infrequent amyloidosis subtype, characterized by the deposition of rounded bodies of protein, occasionally perivascular instead of the usual linear deposits. The most frequently affected organ is the liver, although other organs can also been involved. To date, only eight cases (1-3) of globular amyloidosis of the gastrointestinal tract have been described. Clinical meaning of this morphologic variation of amyloidosis is unknown.

Acute tumour lysis syndrome (TLS) is a catastrophic complication of the treatment of certain neoplastic disorders. It most commonly occurs in association with hematologic malignancies and appears a few hours to a few days after initiation of specific chemotherapy, as the result from the release of intracellular components into the bloodstream due to abrupt malignant cell death. Acute spontaneous TLS is rare, and it has been described in leukemia and lymphoma and in some patients with solid tumors prior to institution of therapy. The syndrome is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia, and acute oliguric or anuric renal failure due to uric acid precipitation within the tubules (acute uric acid nephropathy) and to calcium phosphate deposition in the renal parenchyma and vessels.We report a case of acute spontaneous TLS in a patient with Crohn s disease treated with immunosuppressive drugs, who developed a plasmocytoma, in which serum uric acid concentration attained exceptionally high levels (44 mg/dL). The patient underwent acute oliguric renal failure, which required treatment with hyperhydration, urine alkalinization, urate oxidase and hemodialysis, with a fatal evolution.In conclusion, the present case report has several peculiarities: that of being one of the rare examples of spontaneous TLS, that of showing an exceptionally severe hyperuricemia, probably the highest ever reported in the literature, and that of the possible increased risk of tumours in patients with Crohn s disease taking inmunosuppressives and/or TNF antagonists.

Acute tumour lysis syndrome (TLS) is a catastrophic complication of the treatment of certain neoplastic disorders. It most commonly occurs in association with hematologic malignancies and appears a few hours to a few days after initiation of specific chemotherapy, as the result from the release of intracellular components into the bloodstream due to abrupt malignant cell death. Acute spontaneous TLS is rare, and it has been described in leukemia and lymphoma and in some patients with solid tumors prior to institution of therapy. The syndrome is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia, and acute oliguric or anuric renal failure due to uric acid precipitation within the tubules (acute uric acid nephropathy) and to calcium phosphate deposition in the renal parenchyma and vessels.We report a case of acute spontaneous TLS in a patient with Crohn s disease treated with immunosuppressive drugs, who developed a plasmocytoma, in which serum uric acid concentration attained exceptionally high levels (44 mg/dL). The patient underwent acute oliguric renal failure, which required treatment with hyperhydration, urine alkalinization, urate oxidase and hemodialysis, with a fatal evolution.In conclusion, the present case report has several peculiarities: that of being one of the rare examples of spontaneous TLS, that of showing an exceptionally severe hyperuricemia, probably the highest ever reported in the literature, and that of the possible increased risk of tumours in patients with Crohn s disease taking inmunosuppressives and/or TNF antagonists.

Idiopathic thrombocytopenic purpura is an infrequent extraintestinal manifestation of inflammatory bowel disease. It is particularly rare in association with Crohn's disease. In these cases it presents certain peculiarities with respect to its normal clinical features, occurring more frequently when Crohn's disease is mainly colonic and usually appearing after the diagnosis of Crohn's disease has been made. Moreover, it usually complicates the clinical course of both diseases. We present a case of idiopathic thrombocytopenic purpura in a 14-year-old girl in whom the two diseases first presented simultaneously. The clinical course was poor and both diseases were refractory to habitual treatment.

Background: Scheduled infliximab infusions are effective inducing and maintaining remission in IBD. Compliance with the schedule is important to avoid infusional reactions and loss of response. The aim of this report is to assess the compliance to this treatment in our Unit. Methods: All infliximab infusions received in the IBD Day Care Centre of our hospital since its opening in March 2007 were recorded. Treatment schedule consists in an induction phase 0, 2, 6 weeks and maintenance every 8 weeks. Treatment intensification was prescribed following medical criteria. Infusion delay was defined when the interval between two maintenance doses exceeded 63 days (9 weeks) or when infusion was delayed more than 5 days from calculated date in the induction phase. Intervals when treatment was stopped due to pregnancy, “drug holidays” by medical criteria, etc were excluded. We define “non-adherent patient” when at least three doses and 25% of the total are delayed. Results: 128 patients received 1508 infliximab infusions in our hospital from March 2007 to October 2011. Mean number of infusions was 11.78 (SD 8.9). 60 patients (46.9%) were male and 68 (53.1%) female. The indication was Crohn’s disease in 98 patients (76.5%) and ulcerative colitis in 30 (23.4%). Age at start of the therapy was 39 years (SD 14.6 range 15 77). 74 patients (57.81%) had some dose delayed, being 1.73 the mean number of infusion delayed (SD 2.4). Mean delay was 11.97 days (SD 16.4 median 7 days). Only 19 (14.84%) patients had at least one interval between doses greater than 12 weeks. 13 patients were defined as non-adherent (10,15%) 8 male (53.3%) and 5 female. The type of disease was Crohn in 9 cases (69.2%) and ulcerative colitis in 4 (30.8%). Differences between adherent (AP) and non-adherent patients (NAP) were analyzed: there is no difference in gender or type of disease. Statistically significant differences were found in mean age at start of the therapy (39.44 SD 14.6 AP vs 25.67 SD 5.6 NAP, p < 0.001), number of doses received 11.78 SD 8.9 AP vs 19.15 SD 7.9, NAP p < 0.001), and time on therapy (202.25 SD 9.6 AP vs 99.3 SD 94.9 NAP, p < 0.001). There is no difference in treatment intensification need between both groups; 24 of 115 patients (20.8%) in adherent vs 3 of 13 (23%) in non-adherent (p =NS). Conclusions: Our patients have a good scheduled doses compliance on infliximab therapy in our Unit, even after years of treatment. Risk factors for poor compliance are young patients and need of prolonged therapy. P368 Routine practice of iron infusion therapy in IBD T. Iqbal1 *, G. Rogler2, C. Hoffman3, J. Stein4. 1University Hospital Birmingham, Gastroenterology, Birmingham, United Kingdom, 2University Hospital Zurich, Klinik fur Gastroenterologie und Hepatologie Department fur Innere Medizin, Zurich, Switzerland, 3Vifor Pharma Ltd., Glattbrugg, Switzerland, 4Interdisciplinary Crohn Colitis Centre Rhein Main, Frankfurt, Germany