bluuebunny/crossref_metadata_2025 huggingface dataset:
P311 Detection and characterisation of extra-intestinal manifestations of IBD in clinical office notes using natural language processing
Authors: Stidham R , Yu D , Lahiri S , Vydiswaran V
Published: January 2020

Background

Extra-Intestinal Manifestations (EIM) occur in nearly 40% of patients with IBD and impact both disease experience and therapeutic decision-making, but are not well captured by administrative codes. We aimed to pilot computational natural language processing (NLP) methods to characterise EIMs using consultant notes.

Methods

Subjects with a diagnosis of IBD were identified in a single-centre retrospective review of electronic health records (EHR) between 2014–2017. Gastroenterology (GI) notes were annotated by two reviewers for the presence and activity of EIMs. EIM concepts were identified using NLP methods leveraging UMLS libraries and hand-crafted features. EIM characterisation occurred within a ±25-word window around identified EIMs with classifications including inactive concepts (negated, historical, resolved) and active concepts (improved, worsened, active but unchanged). Decisions on EIM status when repeatedly referenced in a document used section-based weighting for status inference, with greatest to least weight ranking for assessment/plan, subjective, past history, exam, and other, respectively. EIM status was classified as ambiguous when multiple conflicting references were present within the same document of approximately equal weight. Model development and testing used an 80/20 dataset split.

Results

In 4108 unique IBD patients, 1640 (39.9%) had at least 1 EIM identified. The mean age was 41.9 years, 47.2% were male, and 27.0% had biologic exposure. A total of 1240 manually annotated documents (first GI notes) were comprised of 51.1% arthritis, 16.5% ocular, 16.2% psoriasis, with erythema nodosum (EN), pyoderma gangrenosum (PG), and hidradenitis suppurativa (HS) together comprising 16.2% of the cohort. NLP models performed well for correctly classifying both EIM presence and status in a testing set, with overall accuracy, sensitivity, and specificity of 91.2%, 92.9% and 81.8% across all EIMs in notes automatically classified as non-ambiguous (Table 1). NLP methods identified EIM status classification as ambiguous in 38.9% of cases.

Conclusion

NLP methods can detect and classify EIMs with reasonable performance and efficiency compared with traditional manual chart review. Though source document variation and ambiguity present challenges, NLP offers exciting possibilities for population-based research and decision support.
P312 Introduction of bowel ultrasonography for follow-up of paediatric inflammatory bowel disease: A single-centre experience
Authors: Lev Zion R , Focht G , Asayag N , Turner D
Published: January 2020

Background

Bowel ultrasonography (BUS) for imaging of inflammatory bowel disease (IBD) is increasingly recognised as a prominent non-invasive tool to supplement, and in some cases replace traditional endoscopic and imaging modalities, with high sensitivity and specificity. The increasing number of gastroenterologists trained to perform BUS has transformed BUS into a bedside tool to guide routine clinical decision making and accurately monitor response to treatment. However, this process is still in its infancy in paediatric IBD. We present here data on the first 2 years of implementation of BUS performed by a paediatric gastroenterologist (RLT) at the paediatric IBD centre at Shaare Zedek Medical Center in Jerusalem. We aim to describe trends, results and clinical implications of the US studies performed during this period.

Methods

The electronic medical record system was searched for all BUS studies performed on IBD patients by RLT as part of his weekly IBD clinic between 2017–2019. Studies performed on other caregivers’ patients were excluded to ensure uniform documentation and nomenclature. Findings were classified as normal (wall thickness <3 mm), mild (wall thickening 3–4 mm and blood flow < Limberg 3) or significant signs of inflammation (wall thickness ≥4 mm or 3–4 mm with Limberg ≥3). Charts were reviewed to assess the impact of BUS findings on clinical management.

Results

A total of 83 bedside BUS studies were performed on 55 IBD patients (42 with Crohn’s – CD) during the study period, with a mean age of 15.1 ± 3.7 years. Thirty-four had one study (23 with CD), 15 had two (13 with CD) and 6 had three or more (all with CD). Overall, 32 studies were normal, 20 showed mild findings and 30 showed significant inflammation. Four studies found stenosis and one showed an abscess. Follow-up studies of initially active disease showed 10/16 (63%) with improvement, including 9/16 (56%) with sonographic remission. 22/83 (27%) studies were felt upon review to have had a direct impact on clinical decision-making. These included decisions not to switch therapy due to normal BUS despite symptoms, admission due to discovery of an abscess, decision to escalate therapy due to lack of sonographic improvement, and decision to continue adalimumab in the presence of a stricture due to favourable prognostic characteristics as per the CREOLE study.

Conclusion

Bedside BUS is a practical and useful tool that can be integrated into a paediatric IBD clinic, with the ability to provide relevant information in real-time and thus impact on day-to-day patient management.
P318 Artificial intelligence of the neural network-assistant for differential diagnosis of IBD
Authors: Skalinskaya M , Bakulin I , Skazyvaeva E , Rasmagina I , Mashevskii G , Shelyakina N , Ivanova K , Berest D
Published: January 2020

Background

Due to the lack of a ‘gold standard’ in the diagnosis of IBD the differential diagnosis between ulcerative colitis and Crohn′s disease can be very difficult. Verification of diagnosis of IBD takes a long time in majority of cases.

Methods

We have created an artificial neural network (ANN) of the multilayer perceptron type using the Neural Network Toolbox application from the MATLAB application package. Three types of images were used to train the ANN: the norm of the endoscopic picture of the colon, the endoscopic pictures of UC and CD. The first stage is the training of an artificial neural network to distinguish the presence or absence of pathology (29 images of the ‘normal colon’, 14 images of the CD, and 15 - UC). The second stage was to train the ANN to recognise the various forms of IBD. The network was trained on an array of 124 images (62 images of each class of pathologies). Each image was previously converted to the grayscale mode and then into a matrix of pixels. A vector with the number of elements equal to the size of the image was fed to the input of the perceptron.

Results

To solve the task of identifying the pathology a perceptron was built with 32,2784 input neurons, 10 hidden neurons and 2 output neurons which represent the conclusion that the image belongs to one of the two classes: norm or pathology. To solve the problem of differentiating CD and UC a perceptron was created with 364500 input neurons (this value was determined by the image resolution) and 2 output neurons representing the conclusion that the image belongs to one of the two classes: UC or CD. The best result in differentiation of pathology was shown by the ANN of MP 364500 type: 364500-20-2: 2, which total accuracy of recognition was 96,8%. The average accuracy of the developed model was 92.6%. However, in the control sample, the accuracy was 84.2%. This fact indicates that the model should be taught on more images. In addition to the ‘accuracy’ criterion, the ‘completeness’ parameter was used to evaluate the system. ‘Completeness’ for recognition of the image of the norm was the highest and equal to 1, for UC the criterion of ‘completeness’ was 0.89. The lowest ‘completeness’ was obtained when recognising the image of the CD (0.67).

Conclusion

ANN type MP 364500: 364500-20-2: 2 has shown the best results in the set targets. Efficiency in pathology recognition was 96.8%. The efficiency of the created ANN in solving the problem of recognition of different forms of IBD (UC/CD) can be described by the following parameters: specificity (Sp) −78.2%, sensitivity (Se) - 93.1%, accuracy (Ac) - 85,7%. The obtained ANN can be used to solve the problems of classification of endoscopic images of the intestine for the presence of IBD and for differential diagnosis.
P321 Prognosis of intestinal Behcet’s disease according to the Korean consensus-based diagnostic algorithm
Authors: JOO Y Y , Lee B I , Kim S J , Lee H H , Kim J S , Park J M , Cho Y S , Lee K M , Kim S W , Choi H , Choi M G
Published: January 2020

Background

Since the consensus-based diagnostic algorithm for intestinal Behcet’s disease (iBD) was proposed by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases, there were few studies regarding the prognosis of iBD according to the diagnostic algorithm.

Methods

We reviewed the medical records of patients who had ileocecal ulcers with clinical impression of iBD from March 1986 to August 2019 in Seoul St. Mary’s Hospital and evaluated factors at the time of diagnosis which were related with adverse events (AEs, major operation or admission from iBD) and disease-free survival (DFS).

Results

Among 204 eligible patients, a total of 163 were included in the study after exclusion of 41 patients with ileocecal ulcers from other disorders. The male-to-female ratio was 1:1 and the mean age at the time of diagnosis was 48.9 ± 15.9. The number of definite, probable, suspected, and non-diagnostic iBD was 18 (11.0%), 64 (39.3%), 37 (22.7%), and 44 (27.0%), respectively. Patients with definite, probable, and suspected iBD developed more AEs compared with patients with non-diagnostic iBD (p = 0.026). After exclusion of patients with non-diagnostic iBD, univariate analysis showed accompanying haematologic disorders, haemoglobin <10 g/dl, fever, colonic involvement, and hypoalbuminemia (<3.0 g/dl) were significantly related to the development of AEs (all p < 0.05). Multivariate analysis revealed accompanying haematologic disorders, haemoglobin <10 g/dl, fever, and colonic involvement were significantly associated with development of AE (all p < 0.05). Poor DFS was significantly associated with accompanying with haematologic disorders, haemoglobin <10 g/dl, and colonic involvement (p < 0.001, p = 0.022, and p = 0.034) in univariate analysis. Only haemoglobin <10 g/dl was significant in multivariate analysis.

Conclusion

Patients with definite, probable, and suspected iBD have a poor prognosis compared with patients with non-diagnostic iBD. Accompanying with haematologic disorders, anaemia, fever, and colonic involvement at the time of diagnosis are poor prognostic factors in patients with iBD.
P344 Effectiveness of ustekinumab in refractory Crohn’s disease: A real-life experience in a tertiary referral centre
Authors: Truyens M , Geldof J , Dewitte G , Glorieus E , Hindryckx P , Lobaton Ortega T
Published: January 2020

Background

Ustekinumab (UST) is increasingly used in Belgium for moderate to severe Crohn’s disease (CD). The aim of the current study was to describe the real-life experience with UST in our tertiary centre.

Methods

A retrospective study was performed in patients with CD who were started on UST between December 2017 and August 2019. All patients received an initial intravenous (IV) dose of 6 mg/kg body-weight, followed by 8-weekly 90 mg subcutaneous UST. The clinical and endoscopic response was assessed by the physician after induction and during the maintenance phase.

Results

In total, 67 patients were included, of which the majority was refractory to anti-TNF and/or vedolizumab (Table 1). The median duration of treatment was 15 months (IQR 7–25). The clinical and endoscopic response is shown in Table 2. UST was discontinued in 16 patients (23.9%) after a median of 27.5 weeks (IQR 12.3–52.8). Reasons for discontinuation were a loss of response (LOR), including 5 patients who were in need of surgery (n = 10), primary non response (n = 3), malignancy (n = 1), adverse event (n = 1) and patients’ wish (n = 1).

In 29 patients (43.3%) optimisation of UST was necessary due to partial response (n = 13) or due to LOR (n = 16). The optimisation consisted of an IV re-induction in 2 patients, shortening of the dosage interval in 16 patients and a combination of both in 11 patients. The effect of optimisation could be assessed in 22 patients: 10 patients regained a good clinical response and 5 patients attained clinical remission after optimisation. In 7 patients UST was stopped despite optimisation, most often due to persistent LOR.

Conclusion

In this tertiary population of refractory CD patients, treatment with UST resulted in a clinical response in more than 70% of patients. Of note, 43.3% needed optimisation, with a good clinical response in almost half of the cases. The endoscopic response in this preliminary analysis was modest.
P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients
Authors: Liefferinckx C , Fassin M , Thomas D , Minsart C , Cremer A , Amininejad L , Tafciu V , Wambacq V , Van Gossum A , Franchimont D
Published: January 2020

Background

Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences.

Methods

This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay

Results

Demographic and baseline data of our population are presented in Table 1.

The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1).

Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance.

Conclusion

This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.
P348 Clinical outcomes and response predictors of vedolizumab treatment for anti-TNF-failed patients with IBD in Korea: A prospective multicenter cohort study
Authors: Kim J , Yoon H , Lee K M , Jung S A , Park D I , Choi C H , Kim E S , Jung Y , Eun C S , Kim T O , Kang S B , Kim Y S , Seo G S , Lee C K , Im J P , Park S J , Byeon J S , Myung S J , Yang S K , Ye B D
Published: January 2020

Background

Vedolizumab (VDZ) inhibits gut lymphocyte trafficking by binding to α4β7 integrin, which can be effective for patients with Crohn’s disease (CD) or ulcerative colitis (UC). We aimed to investigate the clinical outcomes and response predictors of VDZ treatment for Korean patients with CD or UC, who were previously failed to anti-tumour necrosis factor (TNF) therapy.

Methods

Between August 2017 and November 2019, a total of 159 patients with CD (n = 81) or UC (n = 78) received a VDZ induction therapy from 16 centres and were prospectively enrolled. Of those, patients who were evaluated at week 14 after three induction doses of VDZ (week 0, 2, and 6) were analysed. The co-primary endpoints were corticosteroid-free clinical remission and endoscopic remission/response (for UC) at week 14. We also analysed predictors of corticosteroid-free clinical remission, persistence of vedolizumab and safety.

Results

A total of 153 patients were analysed (CD, 77 [50.3%]; male, 94 [61.4%]; median age, 40 years [range, 17–80]; median disease duration, 8.0 years [range, 0.1–38.0]). All patients had previously experienced failures to at least one anti-TNF agent (one, 105 [68.6%]; two, 44 [28.8%]; three, 4 [2.6%]). Corticosteroid-free clinical remission/response rates in CD and UC patients were 44.6%/51.8% and 39.4%/62.0%, respectively. In patients with UC, endoscopic remission and response rates defined by Mayo endoscopic subscore/ulcerative colitis endoscopic index of severity were 33.8%/14.1% and 55.4%/39.1%, respectively. Multivariate analysis revealed that a clinical response at week 6 were associated with a corticosteroid-free clinical remission at week 14 in both CD (Odds ratio [OR] 33.84, 95% confidence interval [CI] 6.25–183.31, p < 0.001) and UC (OR 12.22, 95% CI 1.30–115.28, p = 0.029). In addition, UC patients with higher baseline levels of C-reactive protein (CRP) and faecal calprotectin were less likely to be in corticosteroid-free clinical remission (CRP > 0.31 mg/dl: OR 0.05, 95% CI 0.00–0.60, p = 0.019; faecal calprotectin > 2,000 μg/g: OR 0.04, 95% CI 0.00–0.93, p = 0.045). The cumulative probabilities of continuing VDZ after one year were 48.7% for CD and 65.7% for UC, respectively. During median 10 months of follow-up periods (range, 3–26 months), disease exacerbation was the most common adverse event (n = 73, 47.7%), followed by nasopharyngitis (n = 23, 15.0%) and arthralgia (n = 19, 12.4%).

Conclusion

In anti-TNF-failed Korean patients with CD and UC, VDZ induction therapy was effective with an acceptable safety profile. Early clinical response and higher inflammatory burden at baseline were associated with corticosteroid-free clinical remission after VDZ induction therapy.
P354 Objectively measured time spent sitting, standing upright, and stepping is associated with disease severity and faecal calprotectin in patients with ulcerative colitis
Authors: Raman M , Vallance J , Lyden K , Alana S , Ohland C , McCoy K , Kaur S , Panaccione R , Reimer R , Taylor L
Published: January 2020

Background

Sitting, lying down, standing upright, and stepping is predominant behaviours occurring throughout the 24-day, yet have not been explored in ulcerative colitis (UC). The purpose of this study was to explore whether objectively measured time spent sitting, lying down, standing upright, and stepping was associated with endoscopic and biomarker-based disease severity in UC patients.

Methods

Patients were recruited from the Foothills Medical Center in Calgary, Alberta. Each patient wore an activPAL™ inclinometer (PAL Technologies Limited, Glasgow, UK) for 7 days (minimum 4 days, and on at least one weekend day). Disease severity was measured using Mayo endoscopic subscore and classified as either normal/mild or moderate/severe. Stool samples were collected and faecal calprotectin (FCP), a measure of gut inflammation, was measured. Serum C-reactive protein (CRP)], a marker of systemic inflammation, was collected. Univariate analysis of covariance (ANCOVA) was used to examine associations between activPALTM behavioural variables, Mayo endoscopic subscore, FCP (< or >250 mg/g) and CRP (< or >5 mg/l). All models were controlled for age, gender, body mass index, and antibiotic use.

Results

21 patients (9 female, 12 male) consented to participate. Patients on average were 36 years of age (SD=8.9) and had a body mass index of 25.7 (2.4). For Mayo endoscopic subscore, 10 patients were normal/mild while 11 patients were moderate/severe. Mean FCP was 2288.6 (5453.9) and mean CRP was 4.9 (10.5). Per day, patients averaged 8443 (2731) steps, 497.6 (149.9) min sitting, 233.4 (72.9) min standing upright, and 536.3 (110.9) min lying down. Mayo endoscopic subscore was negatively associated with total number of steps (D=−3,331 steps, 95% CI: 5,450 to −1,212, p < .01), trended toward decreased upright standing time (D = −108 min/day, 95% CI: −208.2 to −7.7, p = 0.09), and positively with total sitting time (D = 121.2 min/day, 95% CI: −23.5 to 266, p = 0.09). FCP was negatively associated with standing time (D = −102.4 min/day, 95% CI: −206.3 to 1.6, p = .05), trended toward decreased total number of steps (D=−1,956 steps, 95% CI: −4,482 to 569, p = .12), and was not associated with total sitting time (D = 63.8 min/day, 95% CI: −87.8 to 215.4, p = .38). CRP was not associated with any of the activPALTM variables. Time spent lying down was not associated with any UC outcomes.

Conclusion

There was an association between objective measures of daily activity behaviours including total steps, standing time, sitting time and UC biomarkers of disease activity. Future studies should continue to examine daily activity behaviours and UC health outcomes in larger sample sizes.
P361 The effect of immunomodulators and other factors on the persistence of biological agents for Crohn’s disease and ulcerative colitis: data from the Australian population-based registry
Authors: Ko Y , Paramsothy S , Leong R
Published: January 2020

Background

Treatment persistence (duration of medication use) provides real-world evidence on therapeutic effectiveness, tolerability and prescriber and patient preferences. Biological agent persistence in Crohn’s disease (CD) and ulcerative colitis (UC) was compared from a national population-based registry with no hierarchical prescribing order. We hypothesised immunotherapy co-therapy would increase persistence for anti-TNF agents, but not for non-anti-TNF agents due to reduced immunogenicity.

Methods

A randomly selected ten per cent subgroup of the prospectively collected population-based registry from the Australian Pharmaceutical Benefits Scheme between June 2005 and June 2019 was analysed. Treatment persistence of adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ) and ustekinumab (UST) was compared. Factors affecting discontinuation were evaluated using multivariate proportional hazard regression.

Results

886 patients consisting of 1294 lines of therapy (992 CD, 302 UC, 2778 person-years of follow-up) were included. In CD, UST had the highest overall persistence rate (median persistence rate was > 74.6% where 24.6 months is the maximum follow-up time recorded), followed by VDZ, IFX and ADA (p = 0.03) (Figure 1). UST had the highest persistence as first, second and third-line therapies (p < 0.05). In UC, VDZ had the highest persistence rate (median persistence rate was >50.3% where 47.4 months is the maximum follow-up time recorded), followed by IFX and ADA (p < 0.001) (Figure 2). VDZ had the highest persistence rates as first-line therapy (p < 0.001), while second and third-line therapies did not demonstrate significant differences.

Persistence of biological agents correlated with immunomodulator co-therapy in CD (R2: 0.65 p < 0.001) and UC (R2: 0.50 p < 0.001). Thiopurine co-therapy significantly increased persistence for IFX and ADA in CD and UC (p < 0.001) (Figures 3 and 4) but was not significant for UST and VDZ. Methotrexate decreased persistence for VDZ in UC and had no effects on UST, IFX and ADA in UC and CD. In acute-severe UC, there were no significant differences between IFX as monotherapy vs. co-therapy.

On multivariate analysis, higher persistence was seen in males (HR: 0.75 95% CI: 0.59–0.94) and with immunomodulator co-therapy (HR 0.77 95% CI: 0.61–0.97, p = 0.03).

Conclusion

This real-world data reflecting treatment effectiveness, tolerability and patient and prescriber preferences supports the use of UST and VDZ over anti-TNF agents in CD and UC, respectively, to achieve high treatment persistence which is independent of immunomodulator co-therapy, possibly secondary to differing immunogenicity rates. It also highlights the substantial increase in anti-TNF therapy persistence with thiopurine co-therapy, but not with methotrexate.
P377 Risk factors of rectal amputation for Crohn’s disease with perianal lesion
Authors: Yokoo T , Yoshikawa S , Masuda T , Uchida H , Nakao T , Kashizuka H , Yamaoka K , Inagaki M , Okamoto K , Inatsugi N
Published: January 2020

Background

Recently, the importance of top-down therapy is emphasised for early Crohn’s Disease (CD). Especially early use of biologics after onset may prevent rectal amputation or permanent stoma concrete of CD with perianal lesion (CDp). The aim of this study was to evaluate the risk factors of permanent stoma concrete for CDp, and especially we had an interest for the relationship between permanent stoma concrete and length of time it takes for infliximab (IFX) was started to use after onset.

Methods

This is a comparative retrospective study of CDp patients who received IFX therapy at Kenseikai Nara Coloproctology Center between 2002 and 2018. We analysed risk factors of their rectal amputation using logistic regression analysis. Patients were included if they had perianal lesions and received IFX. The cases who received IFX after rectal amputation and who have missing values were excluded. Variables of interest included gender, age at onset and diagnosis, disease duration and location, disease behaviour, smoking, perianal surgical history, timing of IFX use after anoperineal lesion’s onset. Late IFX use was defined as we started to use IFX 2 years after perianal lesion’s onset.

Results

Fifty-four patients were recruited. Mean age was 37 years old, the ratio of males to females was 3.5. Forty-one patients’ disease was located in the small and large intestine, and thirteen patients’ were located in the large intestine. Median follow-up duration was 149 months. Among 54 patients, 10 patients were received rectal amputation or permanent stoma concrete. The univariate analysis revealed that the risk factors for rectal amputation were smoking habit (OR 7.56, 95% CI 1.41–53.88, p-value = 0.007), penetrating type (OR 6.44, 95% CI 1.21–39.22, p-value = 0.013) and Late IFX use (OR 12.47, 95% CI 1.50–589.26, p = 0.011). A multivariate analysis revealed that smoking habit (OR 21.5, 95% CI 1.92–239, p = 0.013) smoking behaviour (OR 21.5, 95% CI 1.92–239.00, p = 0.013) and Late IFX use (OR 16.0, 95% CI 1.01–254, p = 0.049) were independent risk factor for rectal amputation (Table 1).

Conclusion

Smoking and late IFX use may be a significant risk factor of rectal amputation for CDp. Early use of biologics may prevent permanent stoma concrete for CDp.
P390 New features of molecular diagnostics of the regulation of molecular apoptotic pathway in ulcerative colitis
Authors: Iakovlev A A , Volkov A , Shcherbakova I , Tarasova G , Malakhanov S , Bashtovaya O
Published: January 2020

Background

The incidence rate of ulcerative colitis (UC) in Russia is 5–30 cases per 100,000 per year. Molecular pathways of the UC development are not clear. The purpose of the work was to study the molecular interactions of the apoptotic pathway in patients with UC.

Methods

The clinical trial included 92 patients with UC. The clinical presentation of UC depends on the extent of involvement: distal colitis, extensive colitis; the severity of the disease. Criteria of the diagnosis of UC corresponded to ECCO Consensus. Mucosal specimens were graded according to grades 0, 1, 2, 3. The separation of proteins of colon mucosa was based on technologies of IEF, SDS-PAGE, 2DPAGE, by standard sets (MB-HIC C8 Kit, MB-IMAC Cu, MB-Wax Kit, Bruker, USA). The getting of mass-spectrogram was determined by matrix-assisted laser desorption-ionisation time-of-flight mass spectrometry (MALDI-TOF-MS/MS, Ultraflex II, Bruker, USA). Statistical analysis was performed using the software Statistica 10.0 (Statsoft).

Results

HSP2 controls the apoptosis of colonocytes and immune response in damaged colon mucosa by Bcl-2 and IL-17, and is also responsible for the resistance to therapeutic strategies. Anti-apoptotic functions of HSP27 is possible through the interaction with DAXX7, the activation of Akt and the inhibition of the apoptosis. HSP47 interacts with collagen I, II, III, IV and V types, that contributes to the launch of autoimmune process in UC. Caspase 8 protects colonocytes from TNFα-induced cell death through necroptosis mechanism via the blockade of the expression of RIP3. Significant decrease of the expression of PPARγ promotes the activation of STAT and AP-1 signalling pathways, that promotes the increase of the synthesis of IL-2, -6, -8, -12, TNFα, matrix metalloproteinases, the activity of immune and inflammation processes in the colon mucosa.

Results of qualitative proteomic analysis in patients with UC (Tab.)

Conclusion

Proteomic analysis has demonstrated the cascade with caspases 8, 9, 10, the release of cytochrome C from mitochondria, which interacts with Apaf-1, causing activation of caspase-9 in UC colon mucosa. TNF-α activates of initiator caspase-2, -8, and -10 in the apoptotic pathway. The NF-kB pathway induces cellular inhibitors of apoptosis, which function as specific caspase inhibitors in UC colonic mucosa.
P392 Initial experience with fibrin glue combined with infliximab treatment of postoperative anastomotic fistula in patients with Crohn’s disease
Authors: YAO D
Published: January 2020

Background

Postoperative anastomotic fistula is one of the most frequent and potentially life-threatening complications following gastrointestinal resections in patients with Crohn’s disease. The purpose of this study was to report the results of using infliximab to treat postoperative anastomotic fistula in patients with Crohn’s disease.

Methods

A prospective parallel study of fibrin glue combined with infliximab vs. fibrin glue treatment was conducted. Demographic and clinical characteristics and outcomes were compared between the groups.

Results

Thirty-five patients with postoperative anastomotic fistula were evaluated; 14 received fibrin glue combined with infliximab treatment and 21 received fibrin glue treatment. No significant differences in demographic or clinical characteristics were found between the two groups (all p > 0.05). There were two recurrences in the fibrin glue group, and no recurrences in the fibrin glue combined with infliximab group(p = 0.506). No complications occurred in either group.

Conclusion

Infliximab strategy with combining fibrin glue is a simple and effective treatment alternative in the management of postoperative anastomotic fistula in Crohn’s disease.
P396 Pharmacokinetics and circulating total lymphocyte count pharmacodynamic response from single and multiple oral doses of etrasimod in Japanese and Caucasian healthy male subjects
Authors: Lee C A , Acevedo L , Oh D A , Baweja P , Gilder K , Han D , Jhee S , Komori K , Mullin S , Nguyen-Cleary T , Schmelzer K , Tang Y , Zhang J , Grundy J
Published: January 2020

Background

Etrasimod is a selective, sphingosine 1-phosphate receptor modulator in development for chronic immune-mediated inflammatory disorders. We evaluated etrasimod pharmacokinetics (PK) and its pharmacodynamic (PD) effect (lymphocyte count) in Japanese and Caucasian healthy male subjects.

Methods

This phase 1 study comprised 12 men (10 etrasimod; 2 placebo) in each of 4 groups (Japanese, 1 and 2 mg; Caucasian, 1 and 2 mg). Etrasimod or matching placebo was administered once daily (QD) from Days 1 to 7, followed by a 7-day washout and a single dose on Day 15. Blood was intensively sampled on Days 1 and 7 for plasma PK and collected each morning on Days 1 to 15 to measure lymphocyte counts and calculate lymphocyte PD parameters, including Rmin, Rmax, and AUECNet.

Results

Etrasimod peak (Cmax) and total (AUC0-τ) plasma exposure values in Japanese and Caucasian subjects were dose-dependent and showed low-to-moderate inter-subject variability for each dose. Following single and multiple doses, geometric least squares (LS) mean etrasimod exposure values were slightly-to-moderately higher in Japanese subjects compared with Caucasian subjects; however, corresponding dose-body weight normalised etrasimod exposure values were similar indicating the exposure differences appear mainly attributable to bodyweight differences rather than ethnicity. Dose-dependent decreases in median lymphocyte counts were observed in both ethnicities from Days 2 to 8 and increased back to near baseline levels during the washout period. As expected, only LS mean Rmin and AUECNet values were dose-dependent in both ethnicities (table), with none of the evaluated lymphocyte PD parameters being statistically different between Japanese and Caucasian male subjects.

Conclusion

These results demonstrate the lack of clinically meaningful PK or PD (lymphocyte response) ethnic differences between Japanese and Caucasian healthy male subjects and support the potential inclusion of Japanese patients with moderately to severely active ulcerative colitis in global phase 3 clinical trials evaluating an etrasimod 2 mg QD dosing regimen.
P402 Prediction of emergency department re-visit among Crohn’s disease patients: a retrospective study
Authors: Mahajna H , Barash Y , Ungar B , Soffer S , Ben-Horin S , Klang E , Kopylov U
Published: January 2020

Background

Patients with Crohn’s disease are frequently subject to symptoms causing them to seek medical care in emergency departments (ED). Recurrent ED visits are common after initial discharge. The burden of recurrent ED visits of Crohn’s patients is high for the patient and the health care system. We aimed to identify the characteristics of patients with Crohn’s disease who return to the ED within 30 days from discharge.

Methods

We created an electronic data repository of all IBD patients admitted to our tertiary medical centre in the time frame 2012 – 2018. Data included tabular demographic and clinical variables, as well as free-text physician records. For this study, we retrieved consecutive Crohn’s patients who were discharged from the ED. We included only patients with complains that can be attributed to Crohn’s disease exacerbation or complication. Patients without available blood test results were excluded, as well as pregnant women and patients under 18. Patients who returned to the ED in 30 days were compared with those who did not.

Results

Overall, 2148 patients visited our ED with complaints related to Crohn’s disease exacerbation or complication. 1435 (67%) were admitted for hospitalisation. Six hundred and ninety-five (33%) were discharged, of them, 110 (15.8%) returned to the ED within 30 days. Male gender, tachycardia (>100 bpm), pain score >4 (using numerical pain rating scale of 0–10), Albumin <3.5 gr/dl, elevated alkaline phosphatase (>120 IU/l), hyponatremia (<135 meq/l), and anaemia (defined as less than 13.5 gr/dl for males and less than 12.0 gr/dl for females) were found to be associated with ED returns. On multivariate analysis, anaemia (OR 2.44 [95% CI 1.24–4.8]), tachycardia (OR 2.88 [95% CI 1.33–6.2]), and elevated alkaline phosphatase (OR 2.68 [95% CI 1.25–5.78]) were independently associated with ED returns. Of patients with 0, 1, 2, and 3 risk factors for ED re-visits 10%, 17%, 30%, and 33% revisited the ED within 30 days from discharge, respectively.

Conclusion

In our large tertiary centre cohort, recurrent ED visits within 30 days occurred in 16% of the patients. Tachycardia, anaemia and elevated alkaline phosphatase were found to be independently associated with recurrent visits. This model, if validated in prospective studies, may be implemented in order to minimise the burden of recurrent ED visits.
P415 The anti-IL-23/IL-12 agent Ustekinumab is an effective and safe induction therapy in patients with Crohn’s disease refractory or intolerant to anti-TNF: a multicentre Italian study
Authors: Gubbiotti A , Barberio B , Zingone F , D’Incà R , Bertani L , Ferronato A , Urbano M T , Sablich R , Savarino E V
Published: January 2020

Background

There are limited real-life studies in medical literature evaluating the efficacy and safety of Ustekinumab, an Anti-IL-23/Anti IL-12 agent, in patients with Crohn’s disease (CD) who required treatment because of refractoriness or intolerance to previous biological treatments. Thus, the aim of this study was to assess the effectiveness and tolerability of Ustekinumab in anti-TNF refractory or intolerant CD patients.

Methods

All CD patients who completed induction with Ustekinumab in three Italian IBD Units (Padua, Santorso, and Pisa) were enrolled. Patients were evaluated after induction (first intravenous dose followed by a subcutaneous dose at 8 weeks) and clinical (Harvey- Bradshaw-Index) and biochemical data, including faecal calprotectin (FC) and C-reactive protein (CRP) were collected. Information on the need of optimisation (every 12 or 8 weeks) and adverse events were also collected. Continuous and categorical variables were expressed as mean with standard deviation (sd) and frequency with percentages, respectively. Comparisons between variables were conducted using paired t-test and chi-square test. Data were analysed using STATA11.1 software.

Results

Sixty-three patients were included (41 males, mean age 43 ± sd 13.2 years). All of them had previously been treated with at least one biologic agent and 95.2% with oral steroids. The main indications for starting therapy were: previous treatment failure (77.2%) and pharmacological intolerance (17.5%). At the time of the induction, 28.6% patients were under steroid treatment. Post induction, clinical remission was obtained in 63.5% patients, while steroid-free clinical remission in 52.4%. Moreover, a statistically significant reduction of FC (from 916 μg/l to 444 μ/l, p < 0.001) and normalisation of CRP (n = 14, 33.3%; p < 0.001) were observed. After induction, 3 adverse effects were reported, and in two treatment discontinuations was necessary (i.e. 1 case of pyelonephritis and 1 case of a re-activation of entero-cutaneous fistula). Finally, among 63 patients enrolled, 51 (80.9%) were optimised with a maintenance regimen of 8 weeks sub-cutaneous doses.

Conclusion

Our study shows that Ustekinumab seemed is effective in achieving clinical remission and steroid-free clinical remission after induction in the majority of CD patient despite the refractoriness to anti-TNF treatment. Moreover, the drug appeared safe and well tolerated. On the other hand, treatment optimisation to 8 weeks was adopted in most of the patients, in order to guarantee a better outcome.
P418 Filgotinib decreases molecular markers of JAK1 signal transduction in Crohn’s disease: concordance with endoscopy and histopathology
Authors: Reinisch W , Brodbeck J , Galien R , Grant E , Hébuterne X , Kłopocka M , Petryka R , Roblin X , Serone A , Tasset C , Yoon O K , Zaboli S , Vermeire S
Published: January 2020

Background

Filgotinib (FIL) is a JAK1 inhibitor under phase 3 clinical evaluation for treatment of IBD. We conducted a post hoc analysis in a subset of patients with moderately to severely active CD from FITZROY (NCT02048618) to assess the effect of FIL (200 mg QD) on molecular markers of JAK1-related signalling (STAT1 and STAT3 phosphorylation) within epithelium (Ep) and non-Ep regions of intestinal mucosa and explore their correlation to histologic and endoscopic indices.

Methods

Biopsies were collected at baseline (BL) and week 10 (W10) from the most affected area of each predefined bowel segment (ileum, ascending, transverse, descending colon, and rectum). Within-subject matched biopsies for all segments from FIL (n = 42) and placebo (PBO; n = 18) treated patients were scored for histologic (GHAS) and endoscopic (SES-CD) disease activity totalling to 300 segments. Using specific antibodies and IHC, %pSTAT1 and %pSTAT3 positive nuclei within Ep and non-Ep regions of each biopsy were quantified using machine learning (Visiopharm v.2019.06). Basal pSTAT levels assessed from 182 nondiseased (SES-CD = 0 and GHAS = 0) segments were used to determine a threshold for categorising segments as either low or high molecular disease activity (MDA). Agreement between endoscopy or histology and MDA was evaluated by κ and % agreement by segment and all segments combined.

Results

Median basal pSTAT1 was similar between colonic Ep and non-Ep regions (1%–2%), but higher in ileal Ep (5%). Median basal pSTAT3 was higher in non-Ep (3%–5%) vs. Ep (1%–2%) regions across all segments. At BL, MDA was elevated in segments with ulceration (~10%, pSTAT1 and pSTAT3). In segments with GHAS activity subscore ≥2 at BL, both Ep MDA (10%–30%) and non-Ep MDA were elevated (25%–35%) and correlated to histologic activity. In segments with low BL MDA, significantly fewer segments with FIL showed MDA worsening at W10 compared with PBO (both pSTAT1 and pSTAT3). In segments with high BL MDA, FIL treatment improved significantly more segments than PBO; this was evident for pSTAT3 only (table). Concordance between MDA and endoscopy was mostly fair to moderate (κ 0.3–0.5), whereas MDA and histology showed moderate to good concordance (κ 0.4–0.8).

Conclusion

Filgotinib treatment improved JAK1-related MDA within the mucosa of CD patients. Concordance between MDA and clinical indices was highest with histology.
P419 Clinical effectiveness and safety of first-line biologic vedolizumab as a monotherapy or combination therapy in ulcerative colitis and Crohn’s disease patients: results from the EVOLVE study
Authors: Bressler B , Yarur A , Kopylov U , Bassel M , Brett N , Colby C , Lopez C , Saha S , Kifnidi C , Agboton C , Adsul S , Demuth D , Luo M , Wang S , Mantzaris G J
Published: January 2020

Background

There is little long-term research (≥12 months) in ulcerative colitis (UC) and Crohn’s disease (CD) patients investigating the impact on clinical effectiveness of combined (combo) therapy of vedolizumab (VDZ) plus immunomodulators/immunosuppressants (IMMs) compared with VDZ monotherapy. Research suggests the use of concomitant aminosalicylates [5-ASAs] in UC may not bolster effectiveness. Finally, it is unclear if the safety profile differs between VDZ monotherapy and combo therapy. This study described clinical effectiveness and safety outcomes in patients with UC or CD treated with first-line biologic VDZ as monotherapy or combo therapy with IMMs or 5-ASAs (UC only).

Methods

This was a real-world, multi-country (Canada, Greece and the USA), retrospective chart review study of biologic-naïve UC and CD patients (≥18 years old) treated with VDZ (initiated Tx May 2014–March 2018). Data were collected from Tx initiation to the earliest of death and chart abstraction date. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan-Meier method with unadjusted comparisons conducted using the log-rank test. Clinical response and remission were assessed from standard disease measures reported in medical records. Analyses of unadjusted incidence rates (per 100 person-years [PYs]) of disease exacerbations, disease-related surgeries, serious adverse events (SAEs) and serious infections (SIs) were performed. For these analyses in monotherapy vs. VDZ+IMMs, UC and CD patients were combined due to restrictions of sample size and a number of events.

Results

This analysis included 318 patients treated with VDZ (monotherapy: UC = 53, CD = 108; VDZ+IMMs: UC = 22, CD = 24; VDZ+5-ASAs: UC = 111). There were no observed differences in age, sex or disease duration between patients on monotherapy vs. VDZ+IMMs or vs. VDZ+5-ASAs. Data trends in effectiveness outcomes were similar in monotherapy vs. VDZ+IMMs over 24 months (Figure 1). Tx persistence (monotherapy: 71.6%; VDZ+5-ASAs: 82.7%; p = 0.40), clinical remission (monotherapy: 54.3%; VDZ+5-ASAs: 87.7%; p = 0.37) and clinical response (monotherapy: 81.7%; VDZ+5-ASAs: 92.2%; p = 0.54) were also similar between monotherapy and VDZ+5-ASAs over 24 months. Safety outcomes were similar between groups (Figure 2).

Conclusion

Though sample sizes were small, the unadjusted trends in the results of this long-term real-world study suggest that biologic-naïve UC or CD patients treated with VDZ alone may have similar clinical effectiveness outcomes to patients receiving VDZ+IMMs. Trends in data also suggest that in patients with UC, VDZ+5-ASAs may not be more effective than VDZ alone.
P421 Prognostic and therapeutic long-term outcome of patients with ulcerative proctitis: analysis from a large referral centre cohort study
Authors: Dubois E , Moens A , Sabino J , Ferrante M , Vermeire S
Published: January 2020

Background

Data about long-term prognostic and therapeutic outcome of patients with ulcerative proctitis (UP) are scarce. Real-world data are very important as these patients are usually excluded from participation in randomised controlled clinical trials.

Methods

All patients diagnosed with ulcerative colitis limited to the rectum (further defined as UP) and followed at our referral centre between 1998 and 2018, were identified via an automated search of electronic medical records and were reviewed for long-term therapeutic outcome. Treatment success was defined as clinical remission (complete disappearance of UP-related symptoms as judged by the treating physician) and endoscopic inactive disease (Mayo endoscopic sub-score of 0 or 1 on sigmoidoscopy) if available at last follow-up.

Results

From a total of 1561 patients with ulcerative colitis (UC), 168 patients with UP were identified (54% female, mean age at diagnosis 36 years). While the majority (118 patients or 70%) had proctitis since diagnosis, another 50/168 (30%) were diagnosed with left-sided colitis or extensive colitis but had a predominant disease course of proctitis afterwards. Nearly, all patients received treatment with 5-ASA but 71 patients (42%) were refractory to rectal ± oral therapy with 5-ASA and corticosteroids necessitating azathioprine in 41 patients (24%) and/or biological therapies in 59 patients (35%). Azathioprine was started as monotherapy in 34 patients. Anti-TNF was the first-line biological in 45 and vedolizumab in 14 patients. After a median follow-up of 76.5 months (IQR 34.3–143.8), clinical remission was observed in 143 patients (85%) and in 52/71 patients with 5-ASA refractory proctitis (73%). In this last group, clinical remission rates were significantly higher for patients treated with biologicals (44/59 or 75%) as compared with patients treated with azathioprine (8/34 or 24%; p < 0.0001).

Conclusion

Ten per cent of patients with ulcerative colitis from our referral centre cohort had disease confined to the rectum. With a median follow-up of more than 6 years, good clinical outcomes were recorded with 85% of patients achieving clinical remission. Nevertheless, more than one third needed escalation to biologicals to control the proctitis. Long-term outcome in patients on biologicals was superior to azathioprine. Our data do not suggest inferior outcomes for patients with proctitis compared with left-sided or extensive colitis.