Endoscopic Relapse Research Articles

P622 Efficacy of probiotics in inflammatory bowel disease: systematic review and meta-analysis

Abstract Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. We performed a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. Methods: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). Results: The search identified 12,251 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission = 0.86; 95% CI 0.68–1.08). Figure 1. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus placebo in inducing remission in active UC, or in preventing relapse in quiescent UC. However, when only trials of VSL#3 were considered there appeared to be a benefit (RR =0.74; 95% CI 0.63–0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR =1.02 (95% CI 0.85 to 1.23). Figure 2. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus 5-aminosalicylates in Inducing remission in active UC, or in preventing relapse in quiescent UC. There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing endoscopic or clinical relapse of CD after surgically induced remission. Figure 3. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus placebo in inducing remission in active CD, or in preventing relapse in quiescent CD. Conclusions: VSL#3 appears to be effective in inducing remission in active UC, and probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. However, the efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.

Analysis of risk factors - especially different types of plexitis - for postoperative relapse in Crohn's disease.

AIMTo evaluate the presence of submucosal and myenteric plexitis and its role in predicting postoperative recurrence.METHODSData from all patients who underwent Crohn’s disease (CD)-related resection at the University of Szeged, Hungary between 2004 and 2014 were analyzed retrospectively. Demographic data, smoking habits, previous resection, treatment before and after surgery, resection margins, neural fiber hyperplasia, submucosal and myenteric plexitis were evaluated as possible predictors of postoperative recurrence. Histological samples were analyzed blinded to the postoperative outcome and the clinical history of the patient. Plexitis was evaluated based on the appearance of the most severely inflamed ganglion or nerve bundle. Patients underwent regular follow-up with colonoscopy after surgery. Postoperative recurrence was defined on the basis of endoscopic and clinical findings, and/or the need for additional surgical resection.RESULTSOne hundred and four patients were enrolled in the study. Ileocecal, colonic, and small bowel resection were performed in 73.1%, 22.1% and 4.8% of the cases, respectively. Mean disease duration at the time of surgery was 6.25 years. Twenty-six patients underwent previous CD-related surgery. Forty-three point two percent of the patients were on 5-aminosalicylate, 20% on corticosteroid, 68.3% on immunomodulant, and 4% on anti-tumor necrosis factor-alpha postoperative treatment. Postoperative recurrence occurred in 61.5% of the patients; of them 39.1% had surgical recurrence. 92.2% of the recurrences developed within the first five years after the index surgery. Mean disease duration for endoscopic relapse was 2.19 years. The severity of submucosal plexitis was a predictor of the need for second surgery (OR = 1.267, 95%CI: 1.000-1.606, P = 0.050). Female gender (OR = 2.21, 95%CI: 0.98-5.00, P = 0.056), stricturing disease behavior (OR = 3.584, 95%CI: 1.344-9.559, P = 0.011), and isolated ileal localization (OR = 2.671, 95%CI: 1.033-6.910, P = 0.043) were also predictors of postoperative recurrence. No association was revealed between postoperative recurrence and smoking status, postoperative prophylactic treatment and the presence of myenteric plexitis and relapse.CONCLUSIONThe presence of severe submucosal plexitis with lymphocytes in the proximal resection margin is more likely to result in postoperative relapse in CD.

Long-term outcome of inflammatory bowel disease patients with deep remission after discontinuation of TNFα-blocking agents

Background: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNFα-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNFα-blockers are still in remission 24 months later. The aims of this follow-up analysis were to evaluate the long-term remission rate after cessation of TNFα-blocking therapy, the predicting factors of a relapse and the response to restarting TNFα blockers.Methods: The first follow-up data of 51 IBD patients (17 Crohn’s disease [CD], 30 ulcerative colitis [UC] and four inflammatory bowel disease type unclassified [IBDU]) in deep remission at the time of cessation of TNFα-blocking therapy have been published earlier. The long-term data was collected retrospectively after the first follow-up year to evaluate the remission rate and risk factors for the relapse after a median of 36 months.Results: After the first relapse-free year, 14 out of the remaining 34 IBD patients relapsed (41%; 5/12 [42%] CD and 9/22 [41%] UC/IBDU). Univariate analysis indicated no associations with any predictive factors. Re-treatment was effective in 90% (26/29) of patients.Conclusion: Of IBD patients in deep remission at the time of cessation of TNFα-blocking therapy, up to 60% experience a clinical or endoscopic relapse after a median follow-up time of 36 months (95% CI 31–41 months). No individual risk factors predicting relapse could be identified. However, the initial response to a restart of TNFα-blockers seems to be effective and well tolerated.

P-054 Probiotics for Maintenance of Remission in Ulcerative Colitis

Background: Ulcerative colitis (UC) is a chronic relapsing disease characterised by diffuse mucosal inflammation of the colon. Current maintenance treatments have multiple adverse events and an effective treatment with minimal adverse events is desired. Several studies have demonstrated the importance of intestinal flora in the pathogenesis of ulcerative colitis. It has been suggested that modifying the bacterial flora with probiotics may attenuate the inflammatory process and prevent relapses in ulcerative colitis. Five years ago, a Cochrane review found only 4 studies and no evidence regarding the efficacy of probiotics, but much work has been published in recent years. An up to date Cochrane systematic review was performed to determine the efficacy and safety of probiotics for the maintenance of remission in ulcerative colitis. Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and the Cochrane Inflammatory Bowel Disease Group Specialised Trial Register were searched (Inception-January 2015). Manufacturers of probiotics were contacted to identify any unpublished trials. References of trials were also searched for any additional trials. Abstracts were considered for inclusion if full details to judge inclusion and risk of bias were offered or available from the authors. Randomised controlled trials (RCTs) that compared probiotics against placebo or any other intervention for the maintenance of remission in ulcerative colitis were eligible for inclusion. Data extraction and assessment of methodological quality of included studies were independently performed by 2 authors. The main outcome measure was the occurrence of clinical or endoscopic relapse. Results: The search yielded 1006 results, with 34 papers screened in full. Seven studies (n = 887) met the inclusion criteria and were included in the review. Four trials compared probiotics to mesalazine and 3 trials compared probiotics with placebo. The studies ranged in length from 3 to 12 months. The risk of bias was low for randomisation and allocation concealment in one study and unclear in the others. One study was open label, the rest rated as low risk for blinding as double-blinded double dummy trials. The risk of bias was high in one study due to incomplete outcome data and 2 studies due to selective reporting, all the remaining studies low risk. There was no statistically significant difference between probiotics and placebo for maintenance of remission in UC, although there were just 2 small studies with 92 participants (Odds Ratio 0.56; 95% CI 0.22-1.40). Meta-analysis of 4 studies (n = 638) found no statistically significant difference between probiotics and mesalazine (OR 1.29; 95% CI 0.92-1.80). There was no statistically significant difference in the incidence of adverse events (OR 1.16; 95% CI 0.79-1.71). Conclusions: There was no statistically significant difference between probiotics and placebo, although there were just 2 small studies in the pooled analysis at some risk of bias. There was no difference in efficacy found between probiotics and mesalazine on pooled analysis and no difference in adverse events. Further research is proposed to investigate the role of probiotics to maintain remission in UC.

Methotrexate for maintenance of remission in ulcerative colitis.

Methotrexate, a folate antagonist, is an immunosuppressant drug that is effective for treating several inflammatory disorders including Crohn's disease. Ulcerative colitis, a related chronic inflammatory bowel disease, can be challenging to treat. T his updated systematic review summarizes the current evidence on the use of methotrexate for induction maintenance of remission in ulcerative colitis. The objectives of this review were to assess the efficacy and safety of methotrexate for maintenance of remission in patients with ulcerative colitis. We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD/FBD group specialized trials register from inception to June 26, 2014. Study references and review papers were also searched for additional trials. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only. Randomized controlled trials in which methotrexate was compared to placebo or an active comparator in patients with quiescent ulcerative were considered for inclusion. Two authors independently extracted data and assessed the risk of bias for each study. The primary outcome was the occurrence of clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included frequency and nature of adverse events, change of disease activity score and steroid-sparing effect. We calculated the risk ratio and corresponding 95% confidence interval for dichotomous outcomes. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Three trials (165 patients) fulfilled the inclusion criteria. One study compared oral methotrexate (12.5 mg/week) to placebo, another compared oral methotrexate (15 mg/week) to 6-mercaptopurine (6-MP, 1.5 mg/kg/day) or 5-aminosalicylic acid (5-ASA, 3 g/day) and the other compared methotrexate (15 mg/week) in combination sulfasalazine (3 g/day) to sulfasalazine. The placebo-controlled study was rated as low risk of bias. The study comparing methotrexate to 6-MP and 5-ASA was rated as high risk of bias and the study assessing methotrexate and sulfasalazine was rated as unclear risk of bias for sequence generation, allocation concealment and blinding. The placebo-controlled study found no statistically significant differences in the proportion of patients who maintained remission. At nine months, 36% (5/14) of methotrexate patients maintained remission compared to 54% (10/18) of placebo patients (RR 0.64, 95% CI 0.28 to 1.45). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (15 events). The study comparing combination therapy to sulfasalazine found no statistically significant difference in the proportion of patients who maintained remission. At 12 months, 100% (14/14) of patients in the combination group maintained remission compared to 75% (9/12) of sulfasalazine patients (RR 1.32, 95% CI 0.94 to 0.86), A GRADE analysis indicated that the overall quality of the evidence for this outcome was very low due to unknown risk of bias and very sparse data (23 events). There were no statistically significant differences in maintenance of remission rates between methotrexate and 6-MP or between methotrexate and 5-ASA. At 76 weeks, 14% (1/7) of methotrexate patients maintained remission compared to 64% (7/11) of 6-MP patients (RR 0.22, 95% CI 0.03 to 1.45) and 0% (0/2) of 5-ASA patients (RR 1.13, 95% CI 0.06 to 20.71). A GRADE analysis indicated that the overall quality of the evidence from this study was very low due to high risk of bias and very sparse data. Adverse events reported in these studies included transient leucopenia, migraine, nausea and dyspepsia, mild alopecia, mild increase in aspartate aminotransferase levels, peritoneal abscess, hypoalbuminemia, severe rash and atypical pneumonia The results for efficacy and safety outcomes between methotrexate and placebo, methotrexate and sulfasalazine, methotrexate and 6-mercaptopurine and methotrexate and 5-aminosalicylic acid were uncertain. Whether a higher dose or parenteral administration of methotrexate would be effective in quiescent ulcerative colitis is unknown. At present there is no evidence supporting the use of methotrexate for maintenance of remission in ulcerative colitis. More studies are needed to determine the efficacy and safety of methotrexate maintenance therapy in patients with quiescent ulcerative colitis. Large scale methodologically rigorous randomized controlled trials are needed. These studies should investigate higher doses of methotrexate (e.g. 15 to 25 mg/week) and parenteral administration.

High rate of clinical and endoscopic relapse after healing of erosive peptic esophagitis in children and adolescents.

The aim of the present study was to estimate the rate of clinical and endoscopic relapse after initial treatment of erosive peptic esophagitis in children and adolescents. A total of 24 patients (2.1-16.4 years old, mean ± standard deviation [SD] 9.9 ± 3.1; male:female 3) with healed endoscopic erosive esophagitis and without gastroesophageal reflux disease (GERD)-predisposing conditions were followed up for 4 to 32.9 months (mean 20.8 ± 10.6 years). Structured clinical evaluation was performed every other week during the initial treatment and maintenance, and every 3 months after that. Whenever a clinical relapse happened, a new endoscopic evaluation was performed. Severity and frequency were scored on 10-point and 6-point semiquantitative scales, respectively. At baseline, epigastric pain was the most reported symptom (70.8%), with intensity scored as >5 in 88.3% of patients, and median frequency of 3 (weekly; daily in 5, 20.8%). Clinical relapse was detected in 20 of 24 (83.3%) patients after a median period of 14.65 months (95% confidence interval [CI] 6.7-25.7 months). Endoscopic relapse was observed in 9 of 20 (45%) patients after a median of 25.7 months. The dose of lansoprazole needed to heal the esophagitis was not significantly associated with the risk for clinical relapse (hazard ratio [HR] 1.74, 0.94, 7.72, P = 0.06), whereas the body mass index (BMI) was directly associated with endoscopic relapse (HR 1.3, 1, 1.69, P = 0.05). Children with healed erosive esophagitis have up to 83% clinical relapse and of the 83%, 45% had endoscopic relapse. Correlation of endoscopic relapse with clinical symptom is poor. Higher grades of esophagitis and higher BMI are risk factors for endoscopic relapse.

Comparative Efficacy of Pharmacologic Interventions in Preventing Relapse of Crohn’s Disease After Surgery: A Systematic Review and Network Meta-analysis

There are several drugs that might decrease the risk of relapse of Crohn's disease (CD) after surgery, but it is unclear whether one is superior to others. We estimated the comparative efficacy of different pharmacologic interventions for postoperative prophylaxis of CD, through a network meta-analysis of randomized controlled trials. We conducted a systematic search of the literature through March 2014. We identified randomized controlled trials that compared the abilities of mesalamine, antibiotics, budesonide, immunomodulators, anti-tumor necrosis factor α (anti-TNF) (started within 3 months of surgery), and/or placebo or no intervention to prevent clinical and/or endoscopic relapse of CD in adults after surgical resection. We used Bayesian network meta-analysis to combine direct and indirect evidence and estimate the relative effects of treatment. We identified 21 trials comprising 2006 participants comparing 7 treatment strategies. In a network meta-analysis, compared with placebo, mesalamine (relative risk [RR], 0.60; 95% credible interval [CrI], 0.37-0.88), antibiotics (RR, 0.26; 95% CrI, 0.08-0.61), immunomodulator monotherapy (RR, 0.36; 95% CrI, 0.17-0.63), immunomodulator with antibiotics (RR, 0.11; 95% CrI, 0.02-0.51), and anti-TNF monotherapy (RR, 0.04; 95% CrI, 0.00-0.14), but not budesonide (RR, 0.93; 95% CrI, 0.40-1.84), reduced the risk of clinical relapse. Likewise, compared with placebo, antibiotics (RR, 0.41; 95% CrI, 0.15-0.92), immunomodulator monotherapy (RR, 0.33; 95% CrI, 0.13-0.68), immunomodulator with antibiotics (RR, 0.16; 95% CrI, 0.04-0.48), and anti-TNF monotherapy (RR, 0.01; 95% CrI, 0.00-0.05), but neither mesalamine (RR, 0.67; 95% CrI, 0.39-1.08) nor budesonide (RR, 0.86; 95% CrI, 0.61-1.22), reduced the risk of endoscopic relapse. Anti-TNF monotherapy was the most effective pharmacologic intervention for postoperative prophylaxis, with large effect sizes relative to all other strategies (clinical relapse: RR, 0.02-0.20; endoscopic relapse: RR, 0.005-0.04). Based on Bayesian network meta-analysis combining direct and indirect treatment comparisons, anti-TNF monotherapy appears to be the most effective strategy for postoperative prophylaxis for CD.

Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease.

Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease.

Does fecal calprotectin predict short-term relapse after stopping TNFα-blocking agents in inflammatory bowel disease patients in deep remission?

This prospective multicenter study examined whether elevated fecal calprotec tin (FC) concentrations after stopping TNFα-blocking therapy can predict clinical or endoscopic relapse. In addition, we evaluated the impact of histological remission on the relapse risk. We enrolled inflammatory bowel disease (IBD) patients who were in clinical, endoscopic, and FC-based (< 100 μg/g) remission after a minimum 11 months of TNFα-blocking therapy. The patients were followed-up for 12 months after the discontinuation of TNFα-blocking therapy. FC was collected monthly for the first 6 months and thereafter every second month. Ileocolonoscopy was performed at inclusion, at 4 months, at the study end, and at the time of clinical relapse. Of 52 enrolled patients, 49 (16 Crohn's disease, 33 ulcerative colitis/IBD unclassified) provided the stool samples requested and comprised the study group. During the follow-up, 15/49 (31%) relapsed, whereas 34 (69%) remained in remission. Patients relapsing showed constantly elevated FC levels for a median of 94 (13-317) days before the relapse. Significant increase in median FC levels was seen 2 (p = 0.0014), 4 (p = 0.0056), and 6 (p = 0.0029) months before endoscopic relapse. Constantly normal FC concentrations during the follow-up were highly predictive for clinical and endoscopic remission. Normal FC concentrations in patients with remission were associated with histological remission. FC seems to increase and remain elevated before clinical or endoscopic relapse, suggesting that it can be used as a surrogate marker for predicting and identifying patients requiring close follow-up in clinical practice.

1055 Recommendations for Creating a High Quality Endoscopy Report for Inflammatory Bowel Disease Patients: Results From a RAND-Appropriateness Panel

G A A b st ra ct s for Crohn's Disease (SES-CD). In UC or IBDU, clinical and endoscopic relapse was defined by Mayo score. Results: Forty-nine patients (16 CD, 33 UC/IBDU) provided the requested stool samples and comprised the study group. Of the 49 patients 15 (31%, 4 CD [25%], 11 UC/IBDU [33%]) relapsed during the one year follow-up and 34 (69%, 12 CD [75%], 22 UC/IBDU [66%]) remained in remission. Significant increase in median FC levels was seen two (120 μg/g, 0-1867, n = 15, p = 0.0014), four (108 μg/g, 7-650, n = 8, p = 0.0056), and six (120 μg/g, 0-431, n = 6, p = 0.0029) months before the actual relapse. In contrast to those with sustained endoscopic remission, patients relapsing showed constantly elevated FC levels. A cutoff of > 140 μg/g (ROC analysis) predicted relapse with a 79% specificity and a 53% sensitivity. At the moment of clinical and endoscopic relapse 4 out of 15 patients (27%, 1 CD, 3 UC) had FC < 100 μg/g. Interestingly, no difference was found in the relapse rates in patients with FC concentration under 50 or 50-100 at baseline, (p = 0.325) nor in patients with or without acute or chronic inflammatory infiltrate in biopsy specimens at baseline (p = 0.221). No significant difference was seen in median FC levels in patients having endoscopic remission and those with mild endoscopic activity at follow-up colonoscopies. Conclusion: FC seems to rise and remain elevated before the actual clinical or endoscopic relapse, suggesting that FC can be used as a surrogate marker for predicting relapse in patients with IBD, and to identifying patients requiring a close follow-up in clinical practice.

Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies

There is compelling rationale for manipulating the microbiota to treat inflammatory bowel diseases (IBDs). Although studies of animal models of intestinal inflammation produced promising results, trials in humans have been disappointing. In contrast to IBD, the role of the microbiota in the development of irritable bowel syndrome (IBS) only recently has been considered, but early stage results have been encouraging. As pharmaceutical companies develop fewer truly novel agents for treatment of these disorders, consumers seek safer, long-term strategies to deal with chronic symptoms. We assess the rationale for modulating the microbiota for treatment of IBD and IBS, and discuss whether current concepts are simplistic and overstated or simply under-researched. Are claims exaggerated and expectations unrealistic? Difficulties with microbiota terminology and technologies, as well as differences among patients and the heterogeneity of these diseases, pose additional challenges in developing microbiota-based therapies for IBD and IBS.

Rabeprazole 10 mg versus 20 mg in preventing relapse of gastroesophageal reflux disease: a meta-analysis

Background Several randomized controlled trials (RCTs) have compared endoscopic and symptomatic relapses in patients with erosive gastroesophageal reflux disease (GERD). We have summarized current evidence for rabeprazole 10 or 20 mg once daily for GERD maintenance treatment over 1 or 5 years. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched, through August 2012, for eligible RCTs of adults with erosive GERD. The efficacies of rabeprazole 10 and 20 mg/d were compared. Results The search identified 288 citations, and five RCTs containing 1480 patients were considered eligible. Heartburn relapse rates did not differ significantly between patients treated with rabeprazole 10 and 20 mg/d for 1 year (relative risk (RR)=1.29; 95% confidence interval (CI): 0.97-1.72), but differed in patients treated for 5 years (RR=1.274; 95% CI: 1.005-1.615). Endoscopic relapse rates differed significantly between rabeprazole 10 and 20 mg/d for 1 year (RR=1.92; 95% CI: 1.21-3.06), for 5 years (RR=1.667; 95% CI: 1.073-2.589), and in combined 1- and 5-year maintenance trials (RR=1.785; 95% CI: 1.298-2.456). Conclusion Rabeprazole 20 mg/d was superior to rabeprazole 10 mg/d in preventing endoscopic relapse of erosive GERD, but that the two dosages were equivalent in symptomatic relief over 1 year.

1030 Distinctive Urinary Metabolite Profiles Correlate With Microbial Composition and Are Linked With Endoscopic Post-Operative Disease Recurrence in Crohn's Disease Patients

Endoscopic disease recurrence after ileocolonic resection and re-anastomosis in Crohn's disease (CD) patients occurs in a majority of patients. The aim of this study was to examine environmental exposures, the gut microbiome and urinary metabolites in CD patients following ileocolonic resection to determine if specific gut microbes, their metabolites or toxins or environmental factors could be linked with either relapse or remission. Methods: Biopsies were obtained from the neo-terminal ileum after ileocecal resection from CD patients in endoscopic remission (n=20) or in relapse (n=18). Microbial DNA was extracted from biopsies using the QIAamp DNA stool mini kit. Multitag pyrosequencing of the 16S gene was used to characterize the mucosa-associated microbiota, and the RDP 10 classifier used to assign taxonomic groups. Genes encoding for colibactin, C. difficile toxin B, C. perfringens alpha toxin, shiga-like toxin 1 were quantified by qPCR. Urine samples were collected and metabolites measured using 1H NMR. Peak identification was done using Chenomx NMRSuite v7.5 and multivariate analysis performed using MetaboAnalyst 2.0. An environmental questionnaire was obtained that examined early environmental exposures, family history, diet, smoking behaviours, animal exposure and current medication. Principle component analysis (PCA) and support vector machines were used to determine differences between patients with endoscopic relapse and those that remained in remission. Results: Support vector machines applied to total microbial abundance at the genus level and PCA did not show a clear separation between CD patients in relapse or remission. In addition, there were no differences in any toxin encoding genes. In contrast, patients with endoscopic disease recurrence could be separated from patients without ileal inflammation through partial least squares discriminant analysis of urinary metabolites. In addition, correlation analysis showed a positive correlation between urinary metabolites involved in essential processes such as energy production and amino acid metabolism and Bacteroidaceae and negative correlations between amino acid metabolism and Clostridia in the inflamed group. In contrast, the non-inflamed group showed positive correlations between metabolites involved in energy production and Enterobacteriaceae. The most important environmental features associated with disease relapse included smoking cigarettes and/or pipes. Age, gender, years since last surgery, domicile location, or use of immunosuppressants did not differ between CD patients suffering relapse or remaining in endoscopic remission. Conclusions: Recurrence of Crohn's disease after surgery was associated with a unique urinary metabolomics signature that could be linked with specific gut microbes. The major risk factor associated with recurrence of disease was smoking.

1031 Integration of Transcriptomics and Metabonomics: Improving Diagnostics and Phenotyping in Ulcerative Colitis

Endoscopic disease recurrence after ileocolonic resection and re-anastomosis in Crohn's disease (CD) patients occurs in a majority of patients. The aim of this study was to examine environmental exposures, the gut microbiome and urinary metabolites in CD patients following ileocolonic resection to determine if specific gut microbes, their metabolites or toxins or environmental factors could be linked with either relapse or remission. Methods: Biopsies were obtained from the neo-terminal ileum after ileocecal resection from CD patients in endoscopic remission (n=20) or in relapse (n=18). Microbial DNA was extracted from biopsies using the QIAamp DNA stool mini kit. Multitag pyrosequencing of the 16S gene was used to characterize the mucosa-associated microbiota, and the RDP 10 classifier used to assign taxonomic groups. Genes encoding for colibactin, C. difficile toxin B, C. perfringens alpha toxin, shiga-like toxin 1 were quantified by qPCR. Urine samples were collected and metabolites measured using 1H NMR. Peak identification was done using Chenomx NMRSuite v7.5 and multivariate analysis performed using MetaboAnalyst 2.0. An environmental questionnaire was obtained that examined early environmental exposures, family history, diet, smoking behaviours, animal exposure and current medication. Principle component analysis (PCA) and support vector machines were used to determine differences between patients with endoscopic relapse and those that remained in remission. Results: Support vector machines applied to total microbial abundance at the genus level and PCA did not show a clear separation between CD patients in relapse or remission. In addition, there were no differences in any toxin encoding genes. In contrast, patients with endoscopic disease recurrence could be separated from patients without ileal inflammation through partial least squares discriminant analysis of urinary metabolites. In addition, correlation analysis showed a positive correlation between urinary metabolites involved in essential processes such as energy production and amino acid metabolism and Bacteroidaceae and negative correlations between amino acid metabolism and Clostridia in the inflamed group. In contrast, the non-inflamed group showed positive correlations between metabolites involved in energy production and Enterobacteriaceae. The most important environmental features associated with disease relapse included smoking cigarettes and/or pipes. Age, gender, years since last surgery, domicile location, or use of immunosuppressants did not differ between CD patients suffering relapse or remaining in endoscopic remission. Conclusions: Recurrence of Crohn's disease after surgery was associated with a unique urinary metabolomics signature that could be linked with specific gut microbes. The major risk factor associated with recurrence of disease was smoking.

Su1220 Dose Optimization Is Effective in Patients With Ulcerative Colitis Losing Response to Infliximab: A Collaborative Multicentre Retrospective Study

Background: The new therapeutic goal in patients with Crohn’s disease (CD) is long term mucosal healing, due to its proven association with better outcome (better quality of life, fewer complications, less hospitalization). Not all CD patients treated with biologics achieve deep remission and in those patients that achieve it, it can be shortly lived. The aim of our study was to assess the frequency and durability of deep remission in CD patients on biological treatment in a clinical setting. Methods: All CD patients treated with biologics in our department were followed prospectively. Demographical data (age, sex), disease characteristics (Montreal classification, time between diagnosis and start of biological therapy, previous surgeries), type of biologic therapy, other treatments, endoscopic findings were noted. All patients had ileocolonoscopy performed at 6 12 months interval. Deep remission was defined when both clinical (CDAI <150) and endoscopic (no ulcers) remissions were achieved. Results: 49 CD patients, mean age 37±13.06 (20 65) years were followed for a median of 38 (12 72) months. Localization of the disease was ileal in 12.24%, ileocolonic in 32.65% and colonic in 55.1% patients, with 26.53% having associated perianal fistulas. Mean time from diagnosis till biologic therapy was started was of 4.83±4.66 (0 18) years. The majority of patients (41) received Infliximab, the rest Adalimumab. Mean treatment time with biologics was 30.57±15.73 (12 72) months. During this time a mean number of 5.36 (2 11) ileocolonoscopies were performed per patient. Deep remission was achieved in 79.6% of cases after a mean of 8.23±7.52 (2 36) months and was sustained in 51.28% of cases. 48.71% of patients lost deep remission after a mean time of 12±6.48 (3 30) months. In 42.10% of cases (8 patients) after 8.25±3.1 months deep remission was induced again: in 5 cases with biologic dose escalation +/ immunosupressor, one with local budesonide treatment and in 2 cases (with clinical remission) spontaneous healing of ulcerations was observed at follow up ileocolonoscopies, without any therapeutic intervention. Conclusions: In clinical setting deep remission can be achieved in a great proportion of patients after a variable time interval, sometimes over one year of biologic therapy. In patients with flares while on biologic treatment deep remission can be re induced with various therapeutic strategies. Our study showed that transitory, clinically silent, endoscopic relapse is possible during biologic maintenance therapy. P549 Dose optimization is effective in patients with ulcerative colitis losing response to infliximab: a collaborative multicentre retrospective study M. Cesarini1 *, K. Katsanos2, P. Ellul3, P. Lakatos4, K. Papamichael5, F. Caprioli6, E. Tsianos2, G. Mantzaris5, S. Danese7, G. Fiorino7. 1Sapienza University of Rome, Medicina Interna e Specialita Mediche, Rome, Italy, 2University of Ioannina, Greece, 3Mater Dei Hospital, Malta, 4Semmelweis University, Budapest, Hungary, 5Evangelismos Hospital, Athens, Greece, 6University of Milan, Italy, 7 IRCCS Humanitas, IBD Center, Rozzano, Italy

Chronic rhinosinusitis in ex-lepromatous leprosy patients with atrophic rhinitis

Rhino-sinus mucosal involvement is well documented in untreated lepromatous leprosy, but less understood in ex-leprosy patients (i.e. leprosy patients who have been treated and cured) with atrophic rhinitis. Rhino-sinus abnormalities were investigated in 13 ex-lepromatous leprosy patients with atrophic rhinitis, using interviews enquiring about sinonasal symptoms, nasal endoscopy, nasal swab culture and computed tomography. Endoscopic sinus surgery had been performed in three patients. The clinical course, computed tomography findings and nasal biopsy results of these three patients were evaluated. All patients had turbinate atrophy and 6 of the 13 (46.2 per cent) had septal perforation. Paranasal sinus involvement was noted in 9 of 12 examined patients (75 per cent). The most commonly affected sinus was the maxillary sinus (in 8 of 12; 66.7 per cent). All three patients treated by endoscopic sinus surgery experienced relapse and required further surgery. Maxillary sinus irrigation was effective for reduction of persistent symptoms such as postnasal discharge and crusts. Ex-lepromatous leprosy patients with atrophic rhinitis had various rhino-sinus abnormalities and persistent symptoms. These patients had chronic rhinosinusitis because of underlying atrophic rhinitis. These patients required repeated otolaryngological observations together with combined surgery and conservative treatment.

P548 Deep remission: a recurrent feature in patients with Crohn's disease and long term biologic therapy

Background: The new therapeutic goal in patients with Crohn’s disease (CD) is long term mucosal healing, due to its proven association with better outcome (better quality of life, fewer complications, less hospitalization). Not all CD patients treated with biologics achieve deep remission and in those patients that achieve it, it can be shortly lived. The aim of our study was to assess the frequency and durability of deep remission in CD patients on biological treatment in a clinical setting. Methods: All CD patients treated with biologics in our department were followed prospectively. Demographical data (age, sex), disease characteristics (Montreal classification, time between diagnosis and start of biological therapy, previous surgeries), type of biologic therapy, other treatments, endoscopic findings were noted. All patients had ileocolonoscopy performed at 6 12 months interval. Deep remission was defined when both clinical (CDAI <150) and endoscopic (no ulcers) remissions were achieved. Results: 49 CD patients, mean age 37±13.06 (20 65) years were followed for a median of 38 (12 72) months. Localization of the disease was ileal in 12.24%, ileocolonic in 32.65% and colonic in 55.1% patients, with 26.53% having associated perianal fistulas. Mean time from diagnosis till biologic therapy was started was of 4.83±4.66 (0 18) years. The majority of patients (41) received Infliximab, the rest Adalimumab. Mean treatment time with biologics was 30.57±15.73 (12 72) months. During this time a mean number of 5.36 (2 11) ileocolonoscopies were performed per patient. Deep remission was achieved in 79.6% of cases after a mean of 8.23±7.52 (2 36) months and was sustained in 51.28% of cases. 48.71% of patients lost deep remission after a mean time of 12±6.48 (3 30) months. In 42.10% of cases (8 patients) after 8.25±3.1 months deep remission was induced again: in 5 cases with biologic dose escalation +/ immunosupressor, one with local budesonide treatment and in 2 cases (with clinical remission) spontaneous healing of ulcerations was observed at follow up ileocolonoscopies, without any therapeutic intervention. Conclusions: In clinical setting deep remission can be achieved in a great proportion of patients after a variable time interval, sometimes over one year of biologic therapy. In patients with flares while on biologic treatment deep remission can be re induced with various therapeutic strategies. Our study showed that transitory, clinically silent, endoscopic relapse is possible during biologic maintenance therapy. P549 Dose optimization is effective in patients with ulcerative colitis losing response to infliximab: a collaborative multicentre retrospective study M. Cesarini1 *, K. Katsanos2, P. Ellul3, P. Lakatos4, K. Papamichael5, F. Caprioli6, E. Tsianos2, G. Mantzaris5, S. Danese7, G. Fiorino7. 1Sapienza University of Rome, Medicina Interna e Specialita Mediche, Rome, Italy, 2University of Ioannina, Greece, 3Mater Dei Hospital, Malta, 4Semmelweis University, Budapest, Hungary, 5Evangelismos Hospital, Athens, Greece, 6University of Milan, Italy, 7 IRCCS Humanitas, IBD Center, Rozzano, Italy

P125 Ultrasensitive C reactive protein is a marker of endoscopic relapse in patients with ulcerative colitis

P125 Ultrasensitive C reactive protein is a marker of endoscopic relapse in patients with ulcerative colitis

Increased Suppressor of Cytokine Signaling-3 Expression Predicts Mucosal Relapse in Ulcerative Colitis

Most biomarkers predicting mucosal relapse of ulcerative colitis (UC) patients in clinical remission represent low levels of mucosal inflammation. Since SOCS3 expression may increase the vulnerability of intestinal epithelial cells (IECs) to various insults, we investigated whether its expression predicts mucosal relapse in UC patients in clinical remission without any signs of mucosal inflammation. UC patients (n = 32) in clinical, endoscopic, and histological remission were followed up for 9 years. IEC expression of SOCS3, p-STAT3, and p-STAT1 were assessed with biopsies from the baseline colonoscopy, last colonoscopy before relapse, and colonoscopy at relapse. Clinical data, endoscopy, and histology reports were collected from patient charts. Twenty-six (81%) patients had histological relapse, 19 (59%) developed an endoscopic relapse, and 17 (53%) had a clinical relapse during follow-up. SOCS3 expression at first colonoscopy during remission correlated with shorter time to histological, endoscopic, and clinical relapse. SOCS3 expression was increased at the last colonoscopy before relapse, approaching relapse levels, whereas p-STAT3 expression was low during the entire remission. A positive correlation between IEC SOCS3 and its inducer p-STAT1 was shown. SOCS3 IEC expression during remission may be useful in predicting mucosal relapse in patients without any signs of mucosal inflammation. These data strengthen our hypothesis that SOCS3 contributes to enhanced vulnerability of IEC during remission. Thus, SOCS3 levels during remission may function as a therapeutic target for clinical monitoring and early induction of mucosal healing.

P154 First diagnostic endoscopy does not predict disease course except stenosis, while smoking predisposes patients to severe endoscopic relapse in Crohn's disease

P154 First diagnostic endoscopy does not predict disease course except stenosis, while smoking predisposes patients to severe endoscopic relapse in Crohn's disease