bluuebunny/crossref_metadata_2025 huggingface dataset:
P314 C-Reactive protein is associated with depression and anxiety in patients with inflammatory bowel disease
Authors: Rodriguez T , Karpin J , Traboulsi C , Rai V , Rubin D
Published: January 2020

Background

Depression and anxiety are comorbidities of inflammatory bowel disease (IBD). Though previous studies have proposed a relationship between anxiety, depression and IBD, causality and directionality are unknown. We used a novel computerised adaptive testing technology to screen IBD patients for depression and anxiety and compared the screening results to recent measures of C-reactive protein (CRP).

Methods

Consecutive patients at our tertiary IBD clinic were asked to complete the validated CAT-MH™ survey from Adaptive Testing Technologies (Chicago, IL); we then reviewed disease and patient characteristics. CRP measures from within 6 months of survey administration were used and levels ≥5 mg/l were considered positive. Patients who are CRP non-reactive were excluded. Pearson Chi-Square test was used to assess correlation.

Results

134 patients (75 women, 112 Caucasian, 84 Crohn’s disease) participated in the study, 85 of whom had no prior history of psychiatric disorders. We identified 51 patients with depression (46 mild, 3 moderate, 2 severe) and 36 subjects with anxiety (24 mild, 10 moderate, 2 severe). Of the 134 patients recruited for this study, 57 had CRP reported. Median time between CRP measurement and CAT-MH™ administration was 2 days (IQR = 70). Categorical analysis stratified patients with positive and negative CRP who are also positive for depression and/or anxiety. Compared with patients with negative CRP values, patients with positive CRP were more likely to also test positive for depression and anxiety. These results were statistically significant for depression (p = 0.008) and nearly significant for anxiety (p = 0.058) (Figure 1). Quartile analysis of the 21 patients with elevated CRP levels revealed an increasing trend of average depression and anxiety severity scores. However, this correlation was lost when CRP >21 mg/l (Figure 2).

Conclusion

We illustrate the significant association between CRP and depression and anxiety severity scores on the CAT-MH™ survey. These findings suggest a positive relationship between inflammation and depression and anxiety in IBD patients. Physicians should consider patients with elevated CRP levels at risk for these mental health conditions.
P315 Short-chain fatty acid profile in inflammatory bowel disease
Authors: Oliveira L , Yukie Sassaki L , Elisa Valencise Quagli A , Ribeiro de Barros J
Published: January 2020

Background

Short-chain fatty acids (SCFAs) are products of colonic bacterial degradation of dietary fibre. They are important in the colon, affecting the morphology and function of colonocytes. SCFAs consist of a molecule with one to six carbons, of which acetate, propionate and butyrate are the most abundant. In recent decades, it has become apparent that SCFAs can play a key role in the prevention and treatment of metabolic syndrome, intestinal disorders and certain cancers. Crohn’s disease (CD) and ulcerative colitis (UC) are characterised by recurrent chronic intestinal inflammation, probably due to an inadequate immune response coupled with intestinal microbiota imbalance. The aim of this study was to evaluate the profile of SCFA in patients with UC and CD, and compared with non-ill individuals.

Methods

The individuals were divided into three groups: RCU, CD and control, the faeces were donated by them, and the SCFAs were measured by chromatographic analysis using a Thermo Scientific GC-MS coupled to a Thermo ISQ 230ST mass detector. All results are expressed as mean ± SEM.

Results

It was possible to observe a different SCFAs profile between individuals with CD and UC and control where acetate and propionate levels in patients with UC and CD were higher than in non-sick individuals and butyrate with lower levels in individuals with CD and RCU (Graph 1). SCFAs have anti-inflammatory capabilities and also a preferred energy source for colon epithelial cells, as well as lowering the pH of the colon and inhibiting the growth of pathogenic organisms. Dysbiosis decreases butyrate concentrations, which may result in nutrient deficiency at the epithelial level, altering immune responses, as well as acting directly as an anti-inflammatory agent by disabling the NFκB pathway, with a consequent decrease in inflammatory cytokine synthesis.

Conclusion

Thus, the reported results have implications for various physiological and pathological conditions in inflammatory bowel diseases, especially with respect to butyrate and the production of inflammatory mediators, and partly explain the beneficial effects attributed to this fatty acid in the treatment of inflammatory and inflammatory diseases support the realisation of new studies aimed at the development of therapeutic alternatives to the use of conventional anti-inflammatory drugs.
P319 Clinical characteristics of patients with inflammatory bowel disease and metabolic syndrome
Authors: Gubonina I V , Grinevich V , Poluektov M , Kolodin T , Lapteva S , Gamzaeva A , Gubonina N
Published: January 2020

Background

Currently the incidence of patients with Metabolic Syndrome (MS) tends to increase among patients with inflammatory bowel disease (IBD). The purpose of the study is to investigate the course of IBD depending on the presence of MS.

Methods

This cross-sectional analysis was performed on the database of patients with IBD to estimate the frequency of MS presence and study the clinical course (extension of pathologic process, severity and phenotype) of Crohn’s disease (CD) and ulcerative colitis (UC).

Results

347 patients with IBD were included in the investigation: 259 patients with UC and 88 patients with CD. MS was revealed with the same frequency among patients with UC (26 patients, 10.04%) and CD (9 patients, 10.23%). Proctitis (48 patients, 20.6%) and left-sided colitis (121 patients, 51.93%) are usually found among patients with UC without MS while total colitis is significantly more frequent among patients with underlying MS (12, 46.15%, p < 0,05). It was found that patients without MS more often suffered from mild UC (116 patients, 49.79%, p < 0,01) while among patients with MS severe UC occurred more frequently (6 patients, 23.08%, p < 0.05). Among patients with CD and MS, there was no significant correlation between underlying MS and localisation, severity and course of CD.

Conclusion

Patients with UC and MS suffer from a more severe course of UC (as to both the extension of pathologic process and severity) in comparison with the patients with UC without MS. Due to the small quantity of patient with CD and MS insufficient evidence for the influence of MS on the course of CD has been obtained.
P324 Deep enteroscopy after balloon dilatation for differential diagnosis of small bowel stricture
Authors: Lim C H , Kim J
Published: January 2020

Background

Use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin may result in gastrointestinal complications including ulceration, bleeding, and stricture. Chronic fibrosis and chronic ulcerations form bowel stricture which is the most severe stage of NSAIDs induced enteropathy. Capsule endoscopy and balloon enteroscopy may provide detailed information of small bowel mucosal lesions such as longitudinal ulceration suggesting Crohn’s disease. However, more distal or proximal evaluation above stricture is impossible due to severe stricture. Nowadays, balloon dilatation through the enterosope is available and can dilate stricture site by expanding force. This technique allows enteroscope to pass of stricture site and provides accurate evaluation of more proximal or distal small bowel above the stricture. We report our experience of small bowel evaluation after balloon dilatation.

Methods

Nine patients with small bowel stricture and history of NSAIDs between 2012 February and 2019 October were analysed. All patients with small bowel stricture had symptoms including abdominal pain, abdominal fullness, or vomiting and enteroscope could not pass the stricture site. Balloon dilatations were performed with through the scope balloon from 8 mm to 15 mm diameter in these patients. After adequate dilation, enteroscope passage could pass the stricture site. Detailed mucosal evaluation of more proximal or distal small bowel above the stricture was performed.

Results

Successful and adequate balloon dilation of small bowel stricture was achieved in 9 of 9 patients. Additional deep and longitudinal ulceration suggesting Crohn’s disease was found after successful passage of enteroscope in 3 of 9 patients. In 6 of 9 patients, additional chronic shallow ulcerative lesions without deep and longitudinal ulceration was found after eneteroscope passage. Deep enteroscopy after balloon dilatation provided important diagnostic clue and treatment strategy in 3 of 9 patients.

Conclusion

Deep small bowel evaluation above the stricture after balloon dilatation may provide additional and detailed information for differential diagnosis of small bowel stricture.
P339 Assessment of DNA-thioguanine nucleotide identifies patients at risk of thiopurine-induced leukopoenia in inflammatory bowel disease
Authors: Zhu X , Chao K , Gao X , Huang M , Wang X D
Published: January 2020

Background

Thiopurine drugs plays an important role for immunosuppressive therapy in inflammatory bowel disease. The molecular mechanism of the thiopurine toxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to assess the impact of DNA-TGN levels on thiopurine-induced toxicity.

Methods

Patients over 18 years who were diagnosed with IBD and prescribed on thiopurines from February 2019 to August 2019 were recruited. All of them were genotyped with NUDT15 R139C before the thiopurine therapy. A novel assay was established to measure levels of DNA-TGN in blood leucocytes. The DNA-TGN and 6TGN levels were correlated with clinical toxicity.

Results

185 patients with Crohn’s disease and 5 patients with ulcerative colitis were included in this study. DNA-TGN and 6TGN levels could be quantified in 229 patients’ blood samples. Thiopurine-induced leukopoenia (TIL) arose in 19 individuals with the median 6TGN level of 308.0 pmol/8×108 RBC which was not significantly different from the patients without TIL (p = 0.050). However, there was a significant association between DNA-TGN levels and TIL. Patients who developed TIL were identified with a higher DNA-TGN levels compared with those who did not (p = 0.00030, 456.9 (63.3–879.2) vs. 268.9 (45.6–916.8) fmol/μg DNA). The area under the ROC curves of the continuous DNA-TGN concentration to predict TIL was 0.75 (95% CI: 0.63~0.87) and almost 84% (16/19) of the TIL could be explained based on the DNA-TGN cut-off value of 343.9 fmol/μg DNA

Conclusion

This study shows that quantification of DNA-TGN levels can be applied to gauge thioprine therapy and avoid TIL after pre-genotyping NUDT15 R139C in inflammatory bowel disease patients.
P341 Induction of response and remission: a network meta-analysis of induction studies comparing ontamalimab with other treatments for moderate-to-severe ulcerative colitis
Authors: Vickers A , Nag A , Devine B , Sands B E , Panaccione R , Peyrin-Biroulet L , Danese S , Vermeire S , Gorelick K J , Goetsch M , Hartley L
Published: January 2020

Background

Decisions regarding the treatment of ulcerative colitis (UC) should be based on appropriate, high-quality evidence. In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare the efficacy and safety of several treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all other biologics and novel small molecules for which induction study data on response and remission in patients with UC were available.

Methods

A systematic literature review was conducted in November 2017 to identify published randomised controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between all treatments and placebo in terms of efficacy in inducing response and remission. Results were generated for anti-TNF-naïve and -experienced populations.

Results

A total of 14 phase 2 and phase 3 induction studies of the following agents were included: adalimumab (160/80 mg), etrolizumab (100 mg and 300 mg), golimumab (200/100 mg), infliximab (5 mg), ontamalimab (22.5 mg and 75 mg), ozanimod (0.5 mg and 1 mg), tofacitinib (10 mg) and vedolizumab (300 mg). The definitions of response and remission used across trials were consistent. Between-study homogeneity was good and enabled pooling of results. Figure 1 shows odds ratios for induction of response and remission with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments, including ontamalimab, significantly differentiated from placebo in anti-TNF-naïve patients, with the exception of etrolizumab and ozanimod for response and remission, respectively. Tofacitinib (p = 0.0043) and infliximab (p = 0.0013) were superior to adalimumab in inducing response; whereas etrolizumab 100 mg (p = 0.0377), as well as tofacitinib (p = 0.0287) and infliximab (p = 0.0163), was superior to adalimumab in inducing remission.

Conclusion

This study suggests ontamalimab and most other treatments induce response and remission better than placebo. Although conducted before any large-scale head-to-head trials of these drugs, the study suggests a few treatments could be superior to adalimumab in terms of efficacy. However, varying endpoint timings, the combination of phase 2 and 3 data, and lack of control for placebo response could underscore large variances in the data and preclude firm conclusions being drawn.
P350 Perceptions of faecal microbiota transplantation in patients with ulcerative colitis
Authors: Chauhan U K , Popov J , Kalantar M , Wolfe M , Moayyedi P , Marshall J K , Halder S , Kaasalainen S
Published: January 2020

Background

Faecal microbiota transplantation (FMT) is widely being studied for its therapeutic efficacy for a variety of ailments. Despite its gaining popularity, there is a limited understanding of firsthand patient experiences. We explored perceptions of patients who chose to pursue FMT and patients who declined FMT in favour of conventional medications for the treatment of their ulcerative colitis (UC).

Methods

Using qualitative descriptive design, eligible patients were invited to participate in face-to-face semi-structured interviews before and after FMT treatment. Interviews were audiotaped, transcribed, and analysed using a thematic analysis.

Results

Main baseline themes across the FMT (n = 9) and non-FMT (n = 8) groups included: (i) knowledge of FMT, (ii) attitudes around FMT, and (iii) factors contributing to the decision to pursue FMT. Post-FMT themes included: (i) experiences with FMT, and (ii) perceived response to treatment. We found a poor general understanding of FMT across both cohorts, suggesting a need for improving patient education. Non-FMT patients were less likely to have heard or researched FMT in the past due to feelings of ‘it just sounds weird’. Similar concerns were found across both groups, including fear of transmissible infections, cost of experimental therapy, and aversion to stool. Expectations varied between the two groups, with feelings of hope and a sense of ‘last resort’ driving patients to pursue FMT. In contrast, the non-FMT cohort felt a need to further research FMT, explore other treatment options before committing to FMT, and were more likely to describe their disease activity as ‘not at the severe end’. This demonstrates that FMT may be perceived as a ‘last-ditch effort’. Despite initial aversion, the non-FMT group demonstrated an interest in learning more about FMT and felt more open to the possibility of pursuing FMT in the future. The FMT group was more likely to harbour a positive view of natural medicine and classify FMT as natural, while the non-FMT cohort expressed ‘I’m not really into the weird stuff’. Post-FMT, some patients expressed delight in the perceived changes in their symptoms, including improved quality of life, decreased urgency, and less concerns with accidents.

Conclusion

Our results suggest that important motivating factors for pursuing FMT are a perception of naturality and a sense of last resort. With improved education, FMT may pose an acceptable and tolerable treatment option for patients with UC.
P351 Spontaneous intra-abdominal abscesses in Crohn’s disease: The experience of a tertiary centre
Authors: Pereira Guedes T , Sequeira P , Freire L , Castro-Poças F , Rocha A , Santos M , Pedroto I , Lago P
Published: January 2020

Background

Crohn’s Disease (CD) is a transmural inflammatory disease with the possibility of pan-gastrointestinal involvement that could lead in 10–30% of the cases to spontaneous intra-abdominal abscesses (SIAP). Their management is multidisciplinary and personalised. Our goal was to describe the acute management of SIAP in our centre, as well the recurrence rate of abscess and the need of elective surgery.

Methods

We retrospectively reviewed medical records of CD patients who have been admitted for intra-abdominal abscess between April 2009 and August 2017. Patients with secondary or perianal abscesses were excluded.

Results

24 patients were included in this study with a mean time of hospital stay of 22.13 days. Seventy-nine per cent were male, the mean age was 39 years and 50% were smokers. According to Montreal’s Classification: 62,5% were A2, 58,5% L1 and 75% B3 (+p in 8,3%). 9 were under immunosuppressants (IS), 5 under corticosteroid and 4 under anti-TNF(2 combo therapy). All patients were admitted at the emergency room, more frequently with abdominal pain. 20,8% had SIAP as the first manifestation of CD. The most frequent location was inner loops(mean size was 5.54 cm (0.5–13 cm)). All the patients were prescribed with antibiotics; 10 had only antibiotic; 10 also performed percutaneous drainage(PD); 3 underwent surgical drainage, and 1 suffer from spontaneous drainage by an enterocutaneous fistula. Treatment failure was seen in 1 patient of antibiotic and PD groups. 83,3% underwent exclusive enteral nutrition during the hospital stay. 36,4% started corticotherapy. During follow-up, 33,3% added anti-TNF and 15 patients underwent elective surgery ±11.1 month after the discharge. Only 1 relapse of the SIAP was identified after 8 months of discharge. No deaths due CD were observed.

Conclusion

Our population consisted of predominately in young males, with younger age at the diagnose of CD, with ileal involvement and under IS. 5 patients had SIAD as the first manifestation of CD. The majority of the SIAP was controlled in acute context with only 1 patient showing a recurrence of SIAP. 15 patients needed elective surgery in the follow-up period, and 33,3% escalated medical therapy. Our results regarding the need for elective surgery aren’t far from published. More studies with larger cohorts are needed highlighting the individual management of each patient.
P358 Predictors of response to faecal microbiota transplantation in patients with active ulcerative colitis
Authors: Singh A , Sood A , Midha V , Mahajan R , Bansal N , Kaur K , Singh D
Published: January 2020

Background

Faecal microbiota transplantation (FMT) has been shown to be effective for induction of remission in nearly 50% patients with active UC. At present, factors impacting the response to FMT in UC remain unclear.

Methods

Patients with active UC treated with FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22 between September 2015 and March 2019 were analysed. Response to FMT was defined as achievement of clinical remission (Mayo score ≤2, with each sub-score ≤ 1 and endoscopic subscore of 0) at week 22. Patient and disease characteristics and FMT-related factors, considered to affect response to FMT were evaluated in a multivariable logistic regression analysis to determine the predictors of response to FMT. A statistical model was subsequently developed for predicting the success of FMT.

Results

Out of 140 patients with active UC and treated with FMT [mean age 34.29 ± 11.51 years, 65.71% males (n = 92), mean total Mayo score 7.8 ± 2.26], 57 (40.71%) achieved clinical remission. Of the various factors analysed, disease extent E2 (OR 2.34, 95% CI 1.17–4.68, p = 0.016), endoscopic Mayo score 1 (OR 15.375, 95% CI 1.89–125.11, p = 0.011) or 2 (OR 2.12, 95% CI 1.06–4.25, p = 0.035) and number of FMT sessions ≥ 4 (OR 16.74, 95% CI 4.85–57.85, p < 0.001) were found to be associated with response to FMT. An estimated response score was developed and score ≥4 predicted response to FMT with an accuracy of 74.3% [sensitivity 64.79% (95% CI 52.54% to 75.76%); specificity 84.06% (95% CI 73.26% to 91.76%, AUROC 0.834)].

Conclusion

Disease Extent E2, endoscopic mayo score 1 or 2, and number of FMT sessions ≥4 predict response to FMT in active UC. The prediction model has good discriminative power at identifying individuals likely to respond to FMT.
P363 Moderate endurance and muscle training are safe to perform for patients with quiescent or mild active Crohn’s disease and increases their strength
Authors: Seeger W A , Thieringer J , Esters P , Allmendinger B , Schulze H , Dignass A
Published: January 2020

Background

The aim of this study was to examine the practicability and potential influence of moderate endurance and muscle training in patients with quiescent or mildly active Crohn’s disease (CD).

Methods

In this randomised controlled pilot trial 45 CD Patients with a CDAI below 220 were randomised to a control, an endurance or a muscle training group. Participants had to exercise individually for 3 months three times per week. Outcome parameters included disease activity (CDAI), inflammatory parameters and calprotectin, anthropometric data, general well-being (sIBDQ), physical activity (IPAQ), cardiorespiratory fitness as well as strength in the upper and lower extremities.

Results

Forty-five patients were randomised into an endurance (17), muscle (15) and control (13) group, respectively. In the endurance group, the dropout rate was 47% (8) vs. 13% (2) in the muscle group and 0 in the control group. Only one patient discontinued the study due to CD specific symptoms. One patient had to stop the study due to another concomitant disease. One patient in each intervention group was lost to follow-up. The most frequent reason for termination was lack of time and motivation: 37.5% (3) in the endurance group vs. 50% (1) in the muscle group. In both groups, the maximal and average force in the upper and lower extremity increased significantly (all p < 0.04). A statistically significant improvement of the quality of life could only be seen in the endurance group in the subclass ‘mood’ of the sIBDQ (p = 0.03). CDAI decreased in the muscle group in contrast to both other groups, statistical significance, however, was not reached.

Conclusion

This study shows that both endurance and muscle training can be safely performed in patients with mild-to-moderate CD. Muscle training seems to be more feasible for this patient group. Both forms of exercise have beneficial effects on strength and presumably on comorbidities, e.g. bone mineral density and thromboembolic complications. Further research in a larger population and also patients with higher disease activity is needed to examine the effects of moderate exercise on disease activity and immunological changes in CD patients.
P368 Tofacitinib induction efficiency and intracellular cytokine dynamics in ulcerative colitis: Results from clinical practice
Authors: Kolar M , Lukas M , Malickova K , Prochazkova L , Bortlik M , Duricova D , Hruba V , Machkova N , Mitrova K , Vasatko M , Lukas M
Published: January 2020

Background

Tofacitinib is an oral JAK inhibitor approved for the treatment of ulcerative colitis (UC). Its efficiency was proven in registration trials; however, data from clinical practice are insufficient. Our aim was to evaluate response to tofacitinib after 8 weeks in UC patients, and to assess potential predictors of response including early cytokine production shifts.

Methods

Data from consecutive UC patients who started tofacitinib 10 mg b.i.d. were evaluated. Disease activity was assessed by Mayo score at baseline and week 8 together with C-reactive protein (CRP) and faecal calprotectin (FC). Production of IL-4, IL-10, IL-17, TNFα and IFNγ in T-helper cells was determined at baseline and week 4. At week 8, patients with total Mayo 0–5 with endoscopic subscores 0–1 were considered responders. Adverse events were registered at every visit.

Results

Twenty-four patients (41.7% males, 58.3% females), mean age 35.3 ± 11.8 years were included. Mean disease duration was 8.3 ± 5.2 years. In median, the patients were previously treated with two biologic agents; however, 25% of the patients were naive to any biologic therapy. Systemic corticosteroids were present in 41.7% patients at baseline and no patient had concomitant biologic or other immunosuppressive therapy. At week 8, 52.9% of patients responded to therapy. Total Mayo decreased in responders from mean 5.9 ± 3.5 to 1.1 ± 1.3 (p = 0.01), while in nonresponders it changed from 8.0 ± 2.5 to 8.9 ± 2.1 (p = 0.86). Endoscopic subscore decreased from 2.0 ± 1.0 to 0.6 ± 0.7 (p = 0.02) in responders, however, remained stationary in nonresponders (2.9). CRP and FC dropped significantly in responders (6.7 ± 6.2 vs. 2.0 ± 2.2 mg/l, p = 0.04; 1195 ± 1189 vs. 578 ± 654 μg/g, p = 0.05), but not in nonresponders. The responding and nonresponding groups differed significantly in baseline triglycerides, which were higher in nonresponders. Other baseline parameters were comparable. In responders, there was a significant decrease in IL-4 and no change in IL-10, while in nonresponders, there was no change in IL-4 and a significant decrease in IL-10. Tofacitinib was stopped in 23.5% of patients at week 8 due to insufficient response. Two patients reported headaches after treatment initiation and single events of CMV colitis, C. diff. colitis and oral candidiasis occurred.

Conclusion

Tofacitinib was efficient in inducing clinical response with mucosal healing in about 50% of UC patients after 8 weeks of therapy. There was no clear baseline predictor of response, however, considering limited sample, there was also no indication of even multiple biologics failure negatively affecting the response. Preliminary results of cytokine dynamics suggest early IL-4 decrease as a potential biomarker of response, warranting further investigation.
P379 Surveillance with chromoendoscopy to detect new dysplasia in inflammatory bowel disease
Authors: Villar Lucas C , Quiñones Castro R , Vaquero Ayala L , Suárez Álvarez P , Fernández Gundin M J , Sierra Ausín M
Published: January 2020

Background

Inflammatory Bowel Disease patients (IBD) are in a higher risk of colorectal cancer (CRC) than the general population. Studies show that surveillance with chromoendoscopy (CE) is useful for prevention as it detects a higher number of dysplastic lesions, allowing their endoscopic resection and therefore preventing CRC. We aimed to assess our endoscopic results in IBD patients with previous diagnose of dysplasia.

Methods

We performed a retrospective data collection from IBD patients who have had dysplastic lesions in screening chromoendoscopy, performed in our hospital from January 2013 to June 2019. Demographic and clinical data at basal time were collected, as well as endoscopic and histological findings in basal chromoendoscopy and in the first follow-up

Results

353 chromoendoscopies were performed in our Endoscopy Unit in this period and 50 patients showed dysplastic lesions. 14 (28%) of them had already had dysplasia in previous colonoscopies, which were performed with white light and aleatory biopsies. Basal characteristics are shown in the following table.

In the initial chromoendoscopy, an average of 2.57 dysplastic lesions with an average size of 7.59 mm was detected. 70.8% were flat lesions (0-IIa/0-IIb Paris classification) and 53% were located distal to the splenic flexure. 85.7% were tubular adenomas low-grade dysplasia (LGD), 2 cases of high-grade dysplasia (HGD), one serrated polyp and one adenocarcinoma. Twenty-nine follow-up chromoendoscopy have been performed and new dysplasia lesions were found in 41.37% (average of 1.86 lesions, median 8 mm). 55.6% of the lesions were tubular adenomas LGD and 11.1% serrated adenomas LGD. Our analysis shows that patients with new lesions in the second chromoendoscopy had had worse bowel preparation on the first one (7.5 vs. 8.9, p = 0,006). We also found that these patients with new lesions had more flat lesions than sessile ones (70.6% Paris IIa, 23.5% IIb, 5.9% Is, p < 0,005).

Conclusion

Surveillance with chromoendoscopy in IBD patients with previous dysplastic lesions detects new dysplasia in 28% of them and LGD is the most frequent histology. In our sample, finding flat lesions or worse bowel cleaning in the first chromoendoscopy predicts having a higher number of lesions on the follow-up.
P385 A mucosal marker predicting tofacitinib induced an endoscopic response in ulcerative colitis
Authors: Verstockt B , Verstockt S , Alsaoud D , Sabino J , Ferrante M , Vermeire S
Published: January 2020

Background

The pan-Janus kinase (JAK) inhibitor tofacitinib (TFC) has recently been approved for and added to the treatment armamentarium of patients with moderate-to-severe ulcerative colitis (UC). With increasing choices and absence of predictive biomarkers generated from pivotal trials, real-world data are needed to stratify patients based on their molecular fingerprint in order to improve likelihood of response.

Methods

We obtained inflamed colonic biopsies from 52 consecutive patients initiating biological therapy (anti-TNF [n = 16], vedolizumab [VDZ, n = 20]) or TFC [n = 16] for active UC (Mayo endoscopic sub-score ≥2). Treatment choices were made in agreement between patient and physician, but all included patients were naïve for the mode of action initiated. All patients were treated with standard dosage according to the label. The response was defined as a Mayo endoscopic sub-score ≤1 and assessed by weeks 8–14. RNA was extracted and single-end RNA sequencing performed using Illumina HiSeq4000. Sequencing data were analysed through differential gene expression (DESeq2) and an unbiased network biology approach (Weighted Gene Coexpression Network Analysis).

Results

Response was observed in 5 (31.2%) anti-TNF, 13 (65.0%) VDZ, and 5 (31.2%) TFC-treated patients. Previously reported markers for anti-TNF response, including oncostatin M (p = 0.62), TREM1 (p = 0.70) and IL13RA2 (p = 1.0) could not differentiate TFC responders from non-responders. Similarly, the 4-gene vedolizumab signature [MAATS1, PIWIL1, RGS13 and DCHS2] could not discriminate TFC responders from non-responders (p = 0.13). No baseline differences in JAK/STAT-signalling could be identified either. Hence, we performed an unbiased network analysis of all TFC samples which identified 1 cluster of 65 genes, significantly correlating with response (p = 0.006). The hub gene within this network turned out to be the most differentially expressed gene (p = 1.5E−9, fold change [FC] 2.3), with a predictive accuracy for response of 100% (p < 0.001). In contrast, this gene could not predict anti-TNF or vedolizumab induced response (p = 0.13; p = 0.10, respectively). Of interest, baseline expression of the identified marker did not correlate with C-reactive protein, faecal calprotectin, Mayo endoscopic sub-score and other inflammatory markers including IL-6, IL-1B or epithelial markers. In TFC responders, the identified biomarker was significantly reduced by week 8, as compared with baseline (fold change [FC] -3.1, p = 0.0004), but not in non-responders (FC 1.2, p = 0.2) (Figure 1).

Conclusion

We identified a TFC-specific biomarker unrelated to disease severity, increasing the potency of a robust predictive marker based on its underlying mode-of-action. Validation in independent larger datasets is warranted.
P420 A randomised, observer-blinded phase Ib multiple, ascending dose study of UTTR1147A, an IL-22Fc fusion protein, in healthy volunteers and ulcerative colitis patients
Authors: Wagner F , Mansfield J , Geier C , Dash A , Wang Y , Li C , Lekkerkerker A , Lu T
Published: January 2020

Background

Inflammatory bowel disease (IBD) is characterised by gut dysbiosis, weakened epithelial barrier, and a dysregulated immune system. Interleukin-22 (IL-22), an IL-10 family cytokine, has demonstrated efficacy in animal IBD models by promoting intestinal epithelial repair, increasing antimicrobial peptide production, and increasing mucin production via goblet cells1. UTTR1147A is a fusion protein in which IL-22 is linked with the Fc portion of IgG4 to improve the pharmacokinetic (PK) characteristics.

Methods

A phase I study (NCT02749630) was conducted to evaluate the safety, tolerability, PK, and pharmacodynamics (PD) of repeat IV dosing of UTTR1147A in healthy volunteers (HV) and UC patients with centrally read Mayo endoscopic score ≥ 2. 38 HVs and 24 UC patients were given UTTR1147A or placebo at doses ranging from 30 to 90 µg/kg either biweekly or monthly (6:2 UTTR1147A: placebo per cohort). PK and serum PD (REG3A and CRP) were studied across multiple time points and the Mayo Clinic Score was evaluated at baseline, day 30 and day 85.

Results

Overall, UTTR1147A was safe and adequately tolerated in HV and UC patients. The most common adverse events were on-target dermatological effects (dry skin, erythema, and pruritus) that were manageable, monitorable and reversible. Dose-limiting non-serious dermatological toxicities (severe dry skin, erythema, exfoliation, and discomfort) were seen in two HVs and 1 UC patient dosed with 90ug/kg Q2wk. There were 2 unrelated serious adverse events (ankle fracture and cytomegalovirus infection) that eventually resolved. PK analyses showed that UTTR1147A exposures were, in general, dose proportional within HVs and within UC patients, with a mean elimination half-life of ~16 days and ~12 days, respectively. At the same dose level, UC patients showed relatively lower drug exposures than HVs, possibly due to faster drug clearance. Consistent with the Phase Ia2, UTTR1147A directly induced production of serum PD biomarkers REG3A and CRP at all dose cohorts tested compared with placebo. Notably, UC patients appear to have attenuated serum PD responses compared with HV. Clinical response was observed in 7/18 patients, and clinical remission in 5/18 patients treated with UTTR1147A compared with 1/6 and 0/6 placebo patients, respectively.

Conclusion

UTTR1147A demonstrated adequate safety and PK profile in healthy volunteers and UC patients. PD biomarker data demonstrated pharmacological activity of UTTR1147A providing evidence of IL-22R pathway activation. Together with the preliminary signals of efficacy, these data support further investigation of this potential, novel non-immunosuppressive therapy in IBD.
P425 SPOSIB SB2: a Sicilian prospective observational study of patients with inflammatory bowel disease treated with infliximab biosimilar SB2
Authors: Macaluso F S , Fries W , Viola A , Centritto A , Cappello M , Giuffrida E , Privitera A C , Piccillo G , Magnano A , Vinci E , Vassallo R , Trovatello A , Belluardo N , Giangreco E , Camilleri S , Garufi S , Bertolami C , Ventimiglia M , Renna S , Orlando R , Rizzuto G , Grova M , Orlando A
Published: January 2020

Background

Few data on Infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available.

Methods

SPOSIB SB2 is a multicentre, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with Crohn’s disease (CD) or Ulcerative Colitis (UC) starting IFX biosimilar SB2 from the introduction of the drug in Sicily (March 2018) to September 2019 (18 months) were enrolled. Patients were divided into five groups (group A: naive to IFX, naive to anti-TNFs; group B: naive to IFX, previously exposed to other anti-TNFs; group C: switch from IFX originator to SB2; group D: switch from CT-P13 to SB2; group E: multiple switches: from IFX originator to CT-P13 to SB2). The primary end-point was the assessment of safety, in terms of the rate of serious adverse events (SAEs). Secondary end-point was the evaluation of effectiveness, in terms of steroid-free clinical remission and clinical response at 8 weeks and at the end of follow-up, and as treatment persistency.

Results

276 patients (median age 39 years; CD 49.3%, UC 50.7%) were included [group A: 127 (46.0%); group B: 65 (23.6%); group C: 17 (6.2%); group D: 43 (15.6%); group E: 24 (8.7%)]. The cumulative number of infusions of SB2 was 1798, the median follow-up was 8 months (IQR: 4–12 months), and the total follow-up time was 182.7 patient-years (PY). Sixty-seven SAEs occurred in 57 patients (20.7%), with an incidence rate of 36.7 per 100 PY, and 26 of them caused the withdrawal of the drug. The incidence rate ratio (IRR) of SAEs was higher among patients in group B compared with group A (57.7 vs. 30.2 per 100 PY; IRr = 1.91; p = 0.026) and group C (57.7 vs. 18.9 per 100 PY; IRr = 2.93; p = 0.045). The effectiveness of IFX biosimilar SB2 after 8 weeks of treatment was evaluated in patients naïve to IFX (group A + B; n = 192): 110 patients (57.3%) had steroid-free remission, 26 patients (13.5%) achieved a partial response, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank p = 0.15).

Conclusion

This is the first prospective study on the use of IFX biosimilar SB2 in IBD. Safety and efficacy of SB2 seem to be overall similar to those reported for IFX originator and IFX biosimilar CT-P13. A higher incidence of SAEs was observed among patients naive to IFX and previously exposed to other anti-TNFs.
P429 Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilisation in Singapore
Authors: Yeo J Q , Wee H L , Cheen H H , WONG A , Lim T G , Leong W F , Chowbay B , Salazar E , Shim H H , Chan W P W , Kong S C , Ong W C
Published: January 2020

Background

Thiopurines are recommended for maintenance of steroid-free remission in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the Western population. However, it remains a new strategy in Singapore with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate the clinical utility of MM and its impact on healthcare resource utilisation in Singaporean IBD patients.

Methods

A retrospective observational study was conducted at the Singapore General Hospital outpatient IBD Centre. Patients with IBD, baseline MM during 2014–2017 and weight-based thiopurine doses for ≥4 weeks were followed up for 1 year. Actions taken to optimise therapy, metabolite levels before and after the first action were documented. Outcomes assessed included steroid-free remission (SFR), clinical remission (defined as SFR, CRP <9.1mg/l and stool calprotectin <250ug/g), no escalation to anti-tumour necrosis factor or surgery, clinical healthcare resource utilisation and direct healthcare costs.

Results

Ninety IBD patients (50 CD, 40 UC) were included. Among them, 40% had baseline metabolite levels within therapeutic range, 31.1% sub-therapeutic, 21.1% supra-therapeutic and 7.8% shunters. Repeated MM with subsequent dose optimisation helped 67.2% of patients achieve therapeutic levels after 1 year. In particular, dose optimisation and reinforcement of adherence in the sub-therapeutic group recaptured clinical remission in almost 50% of the patients. Overall, 86.7% of patients achieved steroid-free remission and 90% had no therapy escalation or surgery (Table 1). Despite greater outpatient visits and laboratory investigations with MM, the median total healthcare costs at 1 year only increased marginally (S$6,407.66 [shunters] vs. S$5,215.20 [supra-therapeutic] vs. S$4,970.80 [sub-therapeutic] vs. S$4,370.48 [control (within therapeutic range)], p = 0.592) (Table 2).

Conclusion

MM guided timely dose optimisation or therapy escalation for non-responders, identification of non-adherence and reversal of shunting. Therefore, it is a useful clinical tool to optimise thiopurines without significantly increasing healthcare resource costs.
P433 A real-world observational study assessing treatment persistence in ulcerative colitis patients receiving anti-TNF treatment (golimumab or adalimumab)
Authors: Hoque S , Boccaletti S , Puenpatom A , Brown C , Black C , Roberts J , Rajkovic I , Milligan G
Published: January 2020

Background

There are limited published observational data describing both clinical outcomes and treatment persistence rates for anti-TNFs used to treat ulcerative colitis (UC), particularly for golimumab. Based on published literature the outcomes demonstrated in clinical trials do not necessarily translate into clinical practice, highlighting the importance of real-world studies. In this study, we evaluated treatment persistence, switching patterns, and colectomy outcomes between golimumab and adalimumab in the real-world setting.

Methods

A retrospective chart review was conducted across 16 NHS sites in the UK. Data describing demographics, treatment history and colectomy were collected for UC patients treated with either golimumab or adalimumab. Patients were receiving golimumab or adalimumab as first or second-line therapy and initiating treatment between 1 March 2016 and 30 September 2017. Patients enrolled were required to have at least 6 months of data for analyses, and were followed within 12 months where the data were available. Kaplan–Meier analysis was conducted to assess time to discontinuation and also time to colectomy; log-rank tests were used to compare the two treatment arms.

Results

A total of 183 patients, (87 golimumab, 96 adalimumab), mean age was 45.6 years (46.8 years golimumab; 44.4 years adalimumab) and 59.6% were male (71.3% golimumab; 49.0% adalimumab), were included. Overall, 79.8% (78.2% golimumab; 81.3% adalimumab) of patients were receiving their first-line biologic. Treatment persistence with golimumab or adalimumab were relatively similar; 64.4% of golimumab and 64.6% of adalimumab patients remaining on treatment at 12 months (p = 0.7, Figure 1). Of the 65 patients who discontinued treatment within 12 months, 48.4% golimumab and 64.7% adalimumab switched to another biologic. Of those patients who switched, vedolizumab was the most commonly prescribed drug (56.8%), followed by infliximab biosimilar (Inflectra/Remsima) (29.7%) and infliximab (Remicade) (13.5%). Colectomy-free survival was demonstrated by 92.0% golimumab and 91.7% of adalimumab patients 12 months post-treatment initiation (p = 0.7).

Conclusion

The real-world data collected in this study demonstrate comparable treatment persistence for golimumab compared with adalimumab 12 months following treatment initiation. Colectomy-free survival was relatively similar within 1 year.
P451 Short-and long-term effectiveness of ustekinumab in patients with Crohn’s disease: real-world data from a German IBD cohort
Authors: Kubesch A , Rueter L , Farrag K , Krause T , Stienecker K , Hausmann J , Filmann N , Dignass A , Stein J , Blumenstein I
Published: January 2020

Background

The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, Real-World German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers.

Methods

Patients with CD receiving UST treatment in three hospitals and two outpatient centres were included and retrospectively analysed. Rates for short- and long-term remission and response were analysed with the help of clinical (Harvey–Bradshaw Index [HBI]) and biochemical (C-reactive protein [CRP], faecal calprotectin [fCal]) parameters for disease activity.

Results

Data from 180 patients were evaluated. One hundred six patients had a follow-up of at least 8 weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin. The median follow-up was 49.1 weeks (95% CI 42.03–56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 39 (41.9%) responded to UST, and 20 patients (21.5%) were in remission. Steroid-free response and remission at week eight were achieved by 30.1%, and 19.3% of patients. At week 48, 26.9% showed steroid-free response to UST, and 15.1% of the initial patient population was in steroid-free remission. Clinical response at week 16 was independently associated with remission at week 48.

Conclusion

Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment exposed patients.
P454 Serum oncostatin M predicts mucosal healing in Crohn’s disease patients treated with infliximab
Authors: Bertani L , Antonioli L , Fornili M , Fornai M , Tapete G , Albano E , Baiano Svizzero G , Ceccarelli L , Mumolo M G , Baglietto L , Marchi S , Blandizzi C , Costa F
Published: January 2020

Background

A number of Crohn’s Disease (CD) patients fail to respond to infliximab (IFX) treatment. For this reason, the identification of a biomarker suitable to predict treatment outcome represents one of the most intriguing challenges for gastroenterologists. Oncostatin M (OSM) is a member of the interleukin 6 cytokine family, which is upregulated significantly in CD inflamed intestinal mucosa. OSM has been suggested as a promising biomarker to predict the responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases. The aim of the present study was to evaluate the suitability of the evaluation of OSM serum levels as a predictive marker of treatment response to IFX.

Methods

We included CD patients treated with IFX during 2017 and 2018. All patients underwent a colonoscopy at week 54, when treatment response was evaluated in terms of mucosal healing (MH, defined as disappearance of ulcers). At baseline and after 14 weeks of treatment, OSM was evaluated by ELISA on serum samples collected before drug infusion. We assessed also faecal calprotectin (FC) at baseline and week 14. Mann-Whitney test was used to evaluate the correlation between OSM and FC levels at baseline and week 14 with MH at week 54. Spearman correlation between OSM and FC values at baseline and week 14 was computed as well. Logistic regression models to predict MH at week 54 were carried out by the Akaike Information Criterion (AIC) and Area Under the Curve (AUC).

Results

In a cohort of 45 patients (24 males) included in the study, 27 displayed MH. At baseline, OSM levels were significantly lower in treatment responders than non-responders (p < 0.001). Similar results were obtained at week 14, when FC levels also were lower in responders than non-responders (p < 0.001 for both OSM and FC). OSM values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, p < 0.001). The diagnostic accuracy of binary OSM at baseline in predicting MH (AIC = 26, AUC = 0.93) was greater than that of binary FC at week 14 (AIC = 34.7, AUC = 0.89).

Conclusion

These preliminary data suggest that OSM and FC are able to predict the outcome of treatment with IFX. Of note, at variance with FC, the predictive capability of OSM was appreciable at baseline, thus allowing to propose OSM as a promising biomarker for driving therapeutic choices in Crohn’s disease patients.