bluuebunny/crossref_metadata_2025 huggingface dataset:
P225 Using a standardised reporting proforma is associated with improved endoscopic assessment in UC
Authors: KADER R , Middleton P , Ahmad O , Dart R , McGuire J , Sebepos-Rogers G , Segal J , Shakweh E , Samaan M
Published: January 2020

Background

Repeated endoscopic assessments are an essential part of ulcerative colitis (UC) disease management and current guidelines recommend the use of an endoscopic activity score, either the endoscopic Mayo score or Ulcerative Colitis Endoscopic Index of Severity (UCEIS) as treatment targets. These indices have prognostic value, with endoscopic healing associated with favourable short- and long-term outcomes. This multi-centre study aimed to assess the frequency of using endoscopic disease activity scores in UC patients undergoing lower GI endoscopy.

Methods

Lower GI endoscopy reports from patients with UC were retrospectively reviewed from 7 sites in London between April and October 2018. Endoscopy reports were assessed based on the BRIDGe endoscopic reporting criteria including the use of Mayo or UCEIS score. The comparison was made between site factors (specialist IBD centres/non-specialist centres, use of reporting proforma), endoscopist speciality (gastroenterology, surgery or nurse endoscopist), level of training (consultant, registrar or nurse endoscopist) and interest in IBD. Chi-squared was used to compare groups.

Results

899 lower GI endoscopy reports were reviewed. Mayo or UCEIS was used in 51% of cases (453/899). The use of endoscopic scores were significantly higher in gastroenterologists than in surgeons and nurse endoscopists respectively (401/762 (53%) vs. 22/54 (41%) vs. 30/83 (36%)), and higher in registrar trainees than consultants and nurse endoscopists (175/251 (70%) vs. 248/565 (44%) vs. 30/83 (36%)) and in those with a specialist interest in IBD compared with those without (237/409 (58%) vs. 216/490 (44%), p < 0.0001). The use of endoscopic scores was more frequent in specialist IBD centres than in non-specialist centres (417/728 (58%) vs. 36/172 (21%), p < 0.001). One centre used a reporting proforma which was associated with a significantly higher frequency of score use compared with centres without a proforma (202/260 (78%) vs. 251/639 (39%), p < 0.0001).

Conclusion

Reporting of endoscopic disease activity using a standardised scoring system occurs in only half of cases from this large multi-centre cohort. Frequency of use is higher in specialist IBD centres and when performed by gastroenterology specialists. Endoscopy reports from a site that used a standardised reporting proforma were significantly more likely to include an endoscopic index as well as a range of other reporting items. This suggests, at least in part, that endoscopy reporting may be optimised by the introduction of a proforma. Integration of a standardised proforma into reporting software would target all endoscopists performing UC endoscopies regardless of speciality, site or IBD interest.
P249 Use of a point-of-care screening tool to identify depression and anxiety in patients with inflammatory bowel disease
Authors: Karpin J , Rodriguez T , Traboulsi C , Rai V , Rubin D
Published: January 2020

Background

Depression and anxiety are comorbidities of inflammatory bowel disease (IBD). Recent guidelines from the ACG recommend screening for depression and anxiety in IBD patients, but the most effective and efficient way to do this is not established. We used a novel computerised adaptive testing technology to screen IBD patients for depression and anxiety and compared the screening results to disease activity.

Methods

Consecutive patients at our tertiary IBD clinic were asked to complete the validated CAT-MH™ survey from Adaptive Testing Technologies (Chicago, IL). This tool is provided as a text or email link and takes 3–5 min to complete. We reviewed disease and patient characteristics. Categorical variables were assessed using Fisher’s exact test. Clinical remission status was determined by the senior author, blinded to the CAT-MH™ results.

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); 32/51 (62.7%) were previously undiagnosed. Thirty-six subjects tested positive for anxiety (24 mild, 10 moderate, 2 severe); 20/36 (55.6%) were previously undiagnosed. 2/134 patients were positive for suicidal ideation in the past month. Sex, race, type of IBD, surgical history, and number of discontinued medications were not significant (Table 1). Patients with active disease had a significantly greater relative risk for having depression (RR 2.26, 95% CI 1.50–3.39) and anxiety (RR 1.88, 95% CI 1.09–3.24) (Figure 1).

Conclusion

We demonstrate the utility of a novel screening tool for depression and anxiety in IBD patients. Furthermore, we illustrate the positive association between clinically active disease status and the presence of depression and anxiety. Physicians should consider patients with clinically active IBD at risk for depression and anxiety and treat or refer them accordingly.
P296 Quality of reporting of lesions detected at surveillance colonoscopy for IBD
Authors: SHARMA N , Virk A , Nardone O , Smith S , Rimmer P , Shivaji U , Ghosh S , Iacucci M
Published: January 2020

Background

International guidelines of ESGE and ASGE have laid out best practice for documentation of lesions at colonoscopy but few performance indicators have been proposed for surveillance colonoscopy in IBD. A recent publication has highlighted the key performance indicators for surveillance colonoscopy.1 We conducted an audit of current quality of colonoscopy reports documenting lesions detected during surveillance colonoscopy.

Methods

A retrospective analysis of patients who underwent colonoscopy for IBD surveillance over a five year period (2014–2019) at the Queen Elizabeth Hospital, Birmingham, UK was performed. The reports were analysed by independent academic doctors in the gastroenterology division trained in quality of endoscopic report analysis. Optimum criteria for documentation comprised lesion nature (Paris classification), size, documentation of Kudo classification and pit pattern, borders and ulceration.

Results

A total of 1028 colonoscopies were performed for IBD surveillance and the procedures were standardised with routine dye spraying since 2016. The mean patient age was 47.9 years (SD 16.8). Visual evidence of colonoscopic lesions was recorded in 273 cases. Key performance indicators documented for each endoscopic criterion and lesion nature is noted in the Table. Low-grade dysplasia was detected in 61 patients, and carcinoma in 4 patients; no patient had high-grade dysplasia. Benign lesions such as pseudopolyps were detected in the rest. 7 patients had sessile serrated lesions.

Conclusion

At IBD surveillance colonoscopy, documentation of lesions is better for the domains of size, Paris classification and Kudo pit pattern, though not perfect. We also highlight that our colonoscopic documentation of borders and presence of ulcerations is done poorly. It is important that comprehensive training is undertaken to improve documentation as it is essential for the proper choice of management of these lesions.

Reference
P301 Agreement in histologic diagnosis of preneoplastic lesions in inflammatory bowel disease: Results from a national survey in Italy
Authors: Canavese G , Saragoni L , Salviato T , Reggiani Bonetti L , Leoncini G , Baron L , Facchetti M , Vignale C , Villanacci V
Published: January 2020

Background

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of gastrointestinal tract: the inflammatory damage increases the risk of developing preneoplastic and neoplastic conditions. Therefore, a good agreement between pathologists in the detection of preneoplastic lesion is essential in the management of IBD patients, in order to decrease the risk of progression towards neoplastic lesions. An agreement study on 4 pathologists and 38 cases of dysplasia demonstrated a fair agreement (k=0.4).1 A similar study demonstrated that the lowest level of agreement in the category indefinite for dysplasia (κ = 0.251).

Methods

The study consisted of a survey about diagnostic agreement in a series of preneoplastic lesions of IBD-affected patients, based on digital images. The occurrence of the disease and the occurrence of dysplasia were considered in the study. The study enclosed biopsy specimens from 30 colonoscopies and 1 surgical specimen, related to 20 patients with a clinical pattern of IBD from 4 reference centres in Italy. Digital slides were uploaded in an open-source learning platform. For each endoscopy, sampling sites with similar morphology were aggregated in 54 ‘blocks’, and a series of close-ended questions about (A) the occurrence of IBD (active, in remission, absent, not evaluable) and (B) the evidence of dysplasia (LG, HG, absent, undefined) have been submitted for every block. For each case, a final comprehensive evaluation about (1) the occurrence of IBD (present, absent, unsuitable for assessment), (2) the disease classification (ulcerative colitis, Crohn’s disease, unfit for differential diagnosis, not possible for lack of clinical data), (3) the occurrence of IBD-related dysplasia (IBD with dysplasia, dysplasia not IBD-related, dysplasia untestable, absent) and (4) the classification of dysplasia (sporadic adenoma, ALM, DALM, unclassifiable) were provided. Twenty gastrointestinal pathologists from as many centres in Italy were enrolled.

Results

325 of the 400 tests were successfully concluded.

Agreement values

Conclusion

A preliminary data analysis demonstrated a good agreement about the occurrence of IBD, and a lower agreement about the occurrence of dysplasia and its classification in IBD. Analysis of the correlation between agreement and clinical-histologic parameters could provide interesting spotlights on diagnostic algorithms in this field.
P302 Diagnostic accuracy of a serum-based biomarker panel for endoscopic activity in ulcerative colitis
Authors: HOLMER A , Boland B , Singh S , Le H , Neill J , Miralles A , Collins A , Sandborn W , Dulai P
Published: January 2020

Background

The endoscopic healing index (EHI, Monitr, Prometheus Biosciences, San Diego, CA) is a serum-based biomarker panel available for identifying mucosal inflammation in Crohn’s disease.[1] We aimed to study its performance for identifying mucosal inflammation in ulcerative colitis.

Methods

EHI was analysed on serum samples paired with endoscopies from adult patients (≥18 years) participating in a prospective biobank (June 2014 to December 2017). Area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of EHI for endoscopic improvement (EI; Mayo endoscopic sub-score [MES] 0–1) and endoscopic remission (ER; MES 0). Sensitivity for EHI was calculated using a cut-off previously identified for Crohn’s disease which optimised performance for ruling out endoscopic activity (20 points). Alternative cut-offs were explored.

Results

A total of 114 patients were included, with an overall prevalence of 56% and 44% for EI and ER. The AUROC was 0.79 (95% CI 0.70–0.87) for EI and 0.70 (95% CI 0.61–0.80) for ER. A cut-off of 20 points had a sensitivity of 94% (95% CI 83–99%) for ruling out moderate to severe (MES 2–3) endoscopic activity, and a sensitivity of 84% (95% CI 72–92%) for ruling out mild to severe (MES 1–3) endoscopic activity. A cut off of 40 points or higher had > 90% specificity for ruling in moderate to severe (MES 2–3) or mild to severe (MES 1–3) endoscopic activity. (Table 1)

Conclusion

EHI has favourable accuracy in identifying the presence of mucosal inflammation in patients with ulcerative colitis. Although it was not developed and validated for ulcerative colitis, further validation is warranted.

Reference
P320 Thrombocytosis in acute inflammatory bowel disease: a useful biomarker?
Authors: Gazelakis K , Chu I , Martin C , Ward M , Sparrow M
Published: January 2020

Background

Differentiating between infectious gastroenteritis and a flare of inflammatory bowel disease (IBD) can be difficult. Small studies have shown that thrombocytosis may not occur in infectious gastroenteritis. We aimed to determine whether thrombocytosis is a reliable biomarker in distinguishing between these two diagnoses in patients presenting with diarrhoea.

Methods

A retrospective cohort study was conducted at a tertiary referral IBD centre. From January 2000 and December 2018, patients admitted with acute diarrhoea were included. Inclusion criteria were infective gastroenteritis, IBD flare or both. IBD diagnosis was confirmed by standard clinical, radiological and histopathological criteria. Clinical and biochemical parameters were collected.

Results

There were 351 infectious and 506 IBD flare cases. Among these 216 (42.8%) had Crohn’s disease, 276 (54.7%) ulcerative colitis, and 13(2.6%) had IBD-unclassified. Table 1 summarises the main results. Those with acute IBD flare had a longer duration of diarrhoea, bloody diarrhoea, lower albumin and anaemia (p < 0.05 for all comparisons). Patients with infectious diarrhoea were more likely to be older, female, have vomiting and fever and leucocytosis (p < 0.05 for all comparisons). Median platelet count was higher in patients with IBD flares, 334 vs. 220 (p < 0.001) and persisted on multivariate analysis (p < 0.001, OR1.45). On multivariate analysis, other significant associations for IBD flare were age (OR.85, p < 0.001) female sex (OR.23, p < 0.110), blood in faeces (OR 5.98, p < 0.001) vomiting (OR .17, p < 0.001) and albumin (OR.83, p = 0.02). A sub-analysis compared patients with known IBD and infectious gastroenteritis with an identified pathogen (n = 47), with those with an IBD flare alone showed no significant difference in platelet count between groups (419 vs. 465, respectively, p = 0.17).

Conclusion

Our study shows significant differences between clinical and biological markers in patients with acute IBD flares compared with those with infectious gastroenteritis. In particular, thrombocytosis occurs in IBD flares but not in infectious gastroenteritis. This biomarker can be used to differentiate between these diagnoses and guide management.
P326 Reasons for and effectiveness of switching back to originator infliximab after a prior switch to CT-P13 biosimilar
Authors: Mahmmod S , Schultheiss J P D , Tan A C I T L , Lutgens M W M D , Gilissen L P L , Mahmmod N , van der Meulen - de Jong A E , Dijkstra G , van Bodegraven A A , Oldenburg B , Fidder H H
Published: January 2020

Background

In current clinical practice, patients with inflammatory bowel disease (IBD) treated with originator infliximab (IFX) have been or are being switched to biosimilar infliximab (CT-P13) because of lower costs and seemingly similar effectiveness of biosimilars. Over a one-year follow-up, 7%-26% of the patients discontinue CT-P13 treatment. Common reasons for CT-P13 discontinuation are (subjective) loss of response or adverse events. As a result of these newly experienced symptoms, patients are occasionally switched back to treatment with originator IFX. However, not much is currently known regarding reverse switching to originator IFX. We aimed to assess the prevalence of and the specific reasons for reverse switching to originator infliximab within 52-weeks after an initial conversion from originator infliximab to CT-P13 in patients with IBD. Additionally, we evaluated whether reinitiating originator infliximab led to the desired favourable effect and sustained infliximab use.

Methods

In this retrospective, multicentre cohort study, data of IBD patients from eight hospitals in the Netherlands were collected. Adult patients with IBD were eligible for inclusion if they were switched from infliximab originator to CT-P13 and had a follow-up time of at least 52 weeks after initial conversion. Reasons for re-switching were categorised into adverse events or loss of response on the biosimilar. Drug survival was analysed with a time-varying Cox proportional hazards model.

Results

A total of 684 patients with IBD were switched (516 Crohn’s disease, 168 ulcerative colitis). Reverse switching was seen in 74 (10.8%) patients after a median of 140 days (IQR 86–231). Reverse switchers were more often females (70.3% vs. 49.7%, p < 0.001) and had shorter originator treatment (4.0 [IQR 2.6–6.5] vs. 5.2 [IQR 3.0–7.5] years, p = 0.037) than those who stayed on CT-P13. A total of 105 symptoms for switching were reported. IBD-like symptoms (25.7%) and dermatological symptoms (21.9%) were the most common. Four patients had objectified loss of response. All regained response after switching back. IBD-like symptoms and dermatological symptoms were reversible in 74.1% and 87%, respectively. Overall reversibility of symptoms was 73.3%. Cox proportional hazards model with CT-P13/originator infliximab as time-varying covariate, yielded no difference in survival risk (hazard ratio 1.23, 95% CI 0.65–2.33).

Conclusion

Switching back to originator infliximab seems effective in patients with IBD, who experience adverse effects or loss of response after switching from originator to CT-P13. Switching patients back to originator infliximab might, therefore, be justified in case patients experience new side effects or loss of response after switching to CT-P13.
P327 Effectiveness of anti-TNF vs. vedolizumab as a second biologic in IBD: results from national Swedish registers
Authors: Rundquist S , Sachs M , Eriksson C , Olén O , Montgomery S , Halfvarson J
Published: January 2020

Background

We aimed to evaluate the effectiveness of tumour necrosis factor antagonist (anti-TNF) compared with vedolizumab (VDZ) as a second-line biological treatment in IBD.

Methods

A propensity score-matched cohort was created using data from the Swedish National Patient Register, the Swedish Quality Register for IBD (SWIBREG) and the Swedish Prescribed Drug Register. Patients with Crohn’s disease (CD) or ulcerative colitis (UC) exposed to anti-TNF as a first-line biologic, who initiated a second biologic agent 1 May 2014 – 31 December 2016 were included (n = 1363). We compared patients exposed to anti-TNF vs. patients exposed to VDZ as a second-line biologic treatment. The primary outcome was drug continuation rate at 12 months. Secondarily, we assessed survival without hospitalisation (because of IBD, complications of IBD or IBD-related surgery) and survival without IBD-related surgery. Risk of infections was investigated as survival without a) prescription of antibiotics and b) hospitalisation because of infection. Additionally, the proportion of patients on corticosteroids at 12 months was assessed.

Results

After 1:1 propensity score matching, the cohort was restricted to 400 patients (CD, n = 198; UC, n = 202). For CD, estimated drug continuation rate at 12 months was 72.7% in the VDZ-treated patients, compared with 73.7% in the anti-TNF treated patients (Figure 1A). Survival without IBD-related hospitalisation (81.8% vs. 87.9%, p = 0.25), IBD-related surgery (81.8% vs. 88.9%, p = 0.17), prescription of antibiotics (64.6% vs. 70.7%, p = 0.33) and hospitalisation due to infection (94.9 % vs. 87.9%, p = 0.08) did not significantly differ between the groups. Likewise, there was no statistically significant difference in proportions of patients on corticosteroids at 12 months (21.2% vs. 22.2%, p = 0.86). For UC, estimated drug continuation rate at 12 months was 69.3% in the VDZ-treated patients, compared with 62.4% in the anti-TNF treated patients (Figure 1B). VDZ treated patients had lower survival without IBD-related hospitalisation (82.2% vs. 93.1%, p = 0.02) and IBD-related surgery (82.2% vs. 94.1%, p = 0.01). Survival without antibiotics (81.2% vs. 70.3%, p = 0.08) and hospitalisation due to infection (92.1% vs. 92.1%, p = 0.97) as well as corticosteroid treatment at 12 months (17.8% vs. 23.8%, p = 0.30) did not differ significantly between the groups.

Conclusion

In this propensity score-matched cohort, the effectiveness and safety of anti-TNF and vedolizumab appear comparable when used as a second-line biologic in CD. In patients with UC, risk of hospitalisation and surgery was lower in patients treated with anti-TNF. Randomised controlled trials are needed to confirm these findings.

Support provided by Takeda.
P328 Faecal microbiota transplantation as treatment for recurrent Clostridiodes difficile infection in patients with inflammatory bowel disease: Experiences of the Netherlands donor faeces bank
Authors: Van Lingen E , van der Meulen-de Jong A E , Vendrik K E W , Kuijper E J , Terveer E M , Keller J J
Published: January 2020

Background

In recent years Faecal Microbiota Transplantation (FMT) is effectively implemented as an approved treatment approach of refractory Clostridiodes difficile infection (rCDI). In patients with inflammatory bowel disease (IBD) the prevalence of co-infection with CDI is higher than in the general population due to the use of immunosuppressive medication and dysbiosis of the bacteria in the colon. Just a small percentage of IBD patients do have an active CDI infection, not to be confused with carriership. Here we report the treatment course and efficacy of FMT provided by the Netherlands Donor Faeces Bank (NDFB) for IBD patients with rCDI.

Methods

The NDFB was founded to facilitate FMT by providing ready to use donor faeces suspensions for treatment of patients with rCDI in hospitals throughout The Netherlands. A request for FMT is evaluated by the working group (specialists in the fields of Medical Microbiology, Gastroenterology, and Infectious Diseases) to assess the indication of FMT and to formulate a treatment advice for each individual patient taking the comorbidity into account. Prior to FMT, all patients were pre-treated with vancomycin 250 mg for at least 4 days and bowel lavage. In patients with ulcerative colitis as comorbidity, prednisone was added when there was an IBD flare simultaneous. The results of FMT were monitored by prospective collection of outcome data by the NDFB.

Results

Since the start of NDFB in March 2016 until August 2019, 186 FMT requests to treat 176 (r)CDI patients were reviewed within the NDFB working group including 26 patients with rCDI and IBD. In total, 129 patients (of which 14 suffered from IBD) were treated with 143 FMTs for CDI with a cure rate of 89.9% after a single FMT (116/129). FMT was deemed not suitable in 12 of 26 patients with IBD because patients had C. Difficile carriership instead of an active CDI infection. Fourteen IBD patients were treated with FMT (9 ulcerative colitis, 2 Crohn’s disease and 2 indeterminate colitis). 3/14 patients suffered from rCDI with an active episode of IBD. Of the 14 IBD patients treated with FMT, only one patient developed a relapse of a CDI infection within 2-months (total cure rate 92%). This cure rate does not differ from CDI patients without IBD.

Conclusion

In IBD patients with rCDI, FMT is equally effective compared with other patients with rCDI. In case of concurrent activity of IBD, pre-treatment with prednisolone in combination with vancomycin appears to be effective.
P331 Productivity loss in patients with inflammatory bowel disease receiving treatment for iron deficiency anaemia: A comparison of ferric maltol and IV iron
Authors: Howaldt S , Jacob I , Sampson M , Akriche F
Published: January 2020

Background

Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD) and can significantly impair health-related quality of life. IDA imposes a substantial economic burden on healthcare payers resulting primarily from increased medical costs and increased rates of hospital admission. IV iron is currently the main treatment for patients intolerant or unsuitable for standard oral iron. Ferric maltol (FM), a stable oral complex of ferric (Fe3+) iron and maltol, is designed to reduce exposure to elemental iron and thus limit gastrointestinal damage. This analysis compares the productivity loss associated with oral FM and IV ferric carboxymaltose (FCM) treatment.

Methods

Patients with IBD and IDA (haemoglobin [Hb] ≥8.0 g/dl and ≤11.0 g/dl for women or ≥8.0 g/dl and ≤12.0 g/dl for men, and ferritin <30 ng/ml or ferritin <100 ng/ml with transferrin saturation <20%) were randomised to receive FM (30 mg b.i.d) or IV FCM (as per local SmPC) in an open-label, Phase 3b non-inferiority study. The primary endpoint was Hb responder rate (proportion of patients achieving a ≥2 g/dl increase or normalisation of Hb at week 12); the margin for non-inferiority was 20%. Productivity loss was calculated based on the number of days lost due to iron therapy during the initial 12-week study period. The costs associated with lost productivity were calculated using the human capital approach and based on the average gross income from Germany.

Results

250 patients were randomised: 125 to FM and 125 to IV FCM. The primary non-inferiority endpoint was not met. IV FCM treatment resulted in a loss of patient time because IV administration was limited to a hospital or outpatient setting: 50% of patients treated with IV FCM lost at least one full day due to treatment, with 1 in 15 losing 4–6 days (Table 1). Productivity loss was quantified, with IV FCM treatment associated with losses between €0.00 and €107.21 in 50% of patients, €129.17 and €387.51 in 43% of patients and €516.68 and €775.02 in 7% of patients. FM was administered orally by the patient and did not require any in-hospital treatment, there was no treatment linked productivity loss.

Conclusion

IV FCM treatment resulted in productivity loss and disruption to patients’ work and family life due to the need for in-hospital/outpatient IV administration. FM treatment had no associated productivity loss as it was administered orally by the patient. FM has none of the indirect costs associated with IV FCM administration and may provide an oral alternative to IV iron in patients with IBD.
P333 Biologic longevity: Withdrawal of drugs due to remission is rare in clinical practice
Authors: Sharma E , Cunningham G , Dawson P , D’Errico F , Honap S , Lim S , Luber R , Meade S , Pavlidis P , Reynolds R , Irving P
Published: January 2020

Background

Biological medicines are well established in the treatment of inflammatory bowel disease (IBD). The aim of this study was to review the natural history of biologic use in a large cohort of patients from a tertiary centre.

Methods

We performed a retrospective review of prospectively collected records of patients with Ulcerative colitis (UC) and Crohn’s disease (CD) from a single centre. All patients who received ustekinumab, golimumab and vedolizumab between April 2014 and May 2019 were included as were a similar sized cohort of patients who received adalimumab and infliximab. Demographic data, use of concomitant immunomodulation, length of time on drug and reason for stopping treatment were recorded.

Results

The patient cohort is described in Table 1. Median (range) follow-up was 32 (3–61) months. Infliximab and golimumab were used first line in 92 (94%) patients and 83 (87%) patients, respectively. Ustekinumab and vedolizumab were used later on in treatment with 38 patients receiving ustekinumab third line (47%) and vedolizumab being used second line in 52 patients (44%) and third line in 43 (37%) patients. Table 2 describes the reasons for biologic cessation. Other reasons for discontinuation included adverse drug reaction, pregnancy and patient choice. Concomitant immunomodulation at initiation of biologic was seen in 228 (79%) patients on TNF antagonists, 58 (50%) patients on vedolizumab and 44 (54%) patients on ustekinumab.

Conclusion

In CD, adalimumab and infliximab display a longer drug survival compared with ustekinumab and vedolizumab possibly due to treatment positioning. In UC, vedolizumab is associated with more treatment persistence than golimumab. Across all biologics, documented cessation due to remission was low, especially in those biologics that are used second or third line.
P342 Diagnostic accuracy of rectal bleeding and stool frequency in predicting mucosal healing in patients with ulcerative colitis in the tofacitinib OCTAVE Phase 3 induction studies
Authors: Colombel J F , Bushmakin A G , Cappelleri J C , Kulisek N , Santana G O , Lawendy N , Ponce de Leon D , Lakatos P L
Published: January 2020

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In patients with UC, associations between endoscopic findings and patient-reported outcomes, such as stool frequency (SF) and rectal bleeding (RB), are not well described. Here, we evaluated the diagnostic accuracy of Mayo SF and RB subscores to predict mucosal healing (MH) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951).

Methods

This post hoc analysis used data from OCTAVE Induction 1 and 2, two identical, randomised, placebo-controlled, 8-week, Phase 3 studies of tofacitinib for the treatment of patients with moderately to severely active UC.1 SF (Mayo subscore 0–3), RB (Mayo subscore 0–3) and endoscopic findings (Mayo endoscopic subscore [ES] 0–3) were assessed at baseline and at Week 8. MH and endoscopic normalisation were defined as an ES of 0 or 1, or an ES of 0, respectively. Based on two-by-two contingency tables, diagnostic test characteristics for SF and RB were evaluated: positive and negative predictive values, sensitivity and specificity. Kappa statistics (chance-corrected measure of agreement) and Pearson correlations (a measure of association) were also calculated. All available data at Week 8 were used.

Results

A total of 614 and 547 patients received treatment (tofacitinib 15 or 10 mg BID, or placebo) in OCTAVE Induction 1 and 2, respectively. Two-by-two contingency table analyses showed that dichotomised SF (0 vs. ≥1) and RB (0 vs. ≥1) were each or both not good predictors of MH (ES of 0 or 1 vs. ≥2) or endoscopic normalisation (ES 0 vs. ≥1), as ≥1 of the four diagnostic test characteristics was <50% (Table). In OCTAVE Induction 1 and 2, weighted kappa statistics for SF (original metric 0–3) and RB (0–3) vs. ES (0–3) indicated moderate agreement for SF (0.46 and 0.42, respectively), slight agreement for RB (0.19 and 0.15, respectively) and fair agreement for SF and RB (0.40 and 0.34, respectively). Correlations were 0.54 and 0.49 for SF, 0.46 and 0.37 for RB and 0.57 and 0.51 for SF and RB (OCTAVE Induction 1 and 2, respectively), suggesting a modest-to-moderate association.

Conclusion

In patients with UC treated with tofacitinib or placebo in OCTAVE Induction 1 and 2, SF and RB subscores had slight-to-moderate agreement with ES, but were not predictive of MH or endoscopic normalisation. The presence of blood at Week 8 strongly indicated that patients had endoscopic activity, but the absence of blood was associated with MH in <50% of patients. Further analysis is needed to fully understand the relationship between SF, RB and MH.

Reference
P359 Platelet-rich stroma injection (PRS) as a novel surgical treatment of refractory perianal fistulas in Crohn’s disease: A pilot study
Authors: Arkenbosch J , van Ruler O , Dwarkasing R S , Schouten W R , de Vries A C , de Graaf E J R , van der Woude C J
Published: January 2020

Background

Perianal fistulizing Crohn’s disease (FCD) comes with significant morbidity and severe reduced quality of life. Treatment of FCD is challenging and includes immunosuppressive drugs, antibiotics and surgery. All therapies are associated with high recurrence rates. Platelet-rich stroma (PRS) is a combination of platelet-rich plasma (PRP) and stromal vascular fraction (SVF). Autologous PRS includes stromal cells in their matrix with stimulating factors, plays an essential role in wound repair and defence mechanisms against infection and is easy to obtain and inject. Because of its operating mechanism, PRS could be of additional value in patients with refractory FCD. This study aims to assess the feasibility, safety and efficacy of local injection of PRS in patients with refractory FCD.

Methods

After informed consent, 10 patients (age ≥16 years) with refractory FCD were included between March 2018 and July 2019. Exclusion criteria were rectovaginal fistulas, persistent proctitis and pelvic abscesses. All patients underwent surgery with harvesting of subcutaneous fat and venous blood sampling to obtain 6 ml of PRS (1 ml of SVF resp. 5 ml of PRP), excision of the external opening(s), fistula curettage, and injection of PRS in the fistula wall and closure of the internal opening. A pre- and postoperative MRI was performed. Endpoints were clinical outcome, both closure and absence of discharge at physical examination, patient-reported outcome (no effect/moderate effect/major effect), as well as radiological outcome (van Assche score). From 3 months postoperative, re-injection of PRS was considered in patients with unfavourable clinical and/or radiological outcome.

Results

All patients (4:6 female:male; median age 33 (IQR 22.9–38.7) had infralevatoric fistulas with a median van Assche score of 17 [range 14–20] without rectal involvement and abscesses. Median follow-up was 6 months [4–12]. The median duration of FCD was 4 years (IQR 2–5). The median number of drugs given were 4 [1–7] and number of operations 3 [2–3], including stoma formation in 2 patients. Crohn’s disease activity outside the anorectum was present in all patients. 7 patients underwent 1 PRS injection and 3 patients 2 injections. There were no complications of the PRS injection. Fistula closure was present in 5 patients and open in 5 patients, of which 2 patients had no signs of discharge. One patient underwent restoration of bowel continuity. Of 7 postoperative MRIs available to date, median decrease of van Assche score was 4 (17 vs. 13)[0–15]. Patient-reported outcome was major effect in 4, moderate effect in 3, and no effect in 3 patients.

Conclusion

Autologous PRS appears to be feasible, safe and promising in the treatment of refractory perianal fistulizing Crohn’s disease.
P369 Mycobacterium tuberculosis infection among patients with inflammatory bowel disease under biologics: experience of Croatian Tertiary Centre
Authors: Ogresta D , Bišćanin A , Tomašić V , Dorosulić Z , Kralj D , Forgač J , Ćaćić P , Lerotić I , Hrabar D
Published: January 2020

Background

Mycobacterium tuberculosis infection (TB) causes a huge number of deaths in the world. A majority (95%) of infections remain asymptomatic, defined as latent tuberculosis (LTB). The estimated incidence rate of TB in Croatia is 10.6 cases per 100 000 inhabitants. Patients with inflammatory bowel diseases (IBD) usually require immunosuppressive therapies which puts them at higher risk for infection. LTB diagnosis and prophylactic treatment are recommended for all patients starting biologics.

Methods

A single-centre retrospective study in the continental part of Croatia included all IBD patients who started treatment with biologics and have presented with TB or LTB from January 2016 till September 2019. The aim was to evaluate the prevalence of LTB among patients with IBD before starting biologic therapy, and TB reactivation during treatment with biologics. All patients underwent Interferon Gamma Release Assay (IGRA) and X-ray. Active infection was excluded or diagnosed using clinical history, bronchoscopy, CT scan and sputum stain for Mycobacteria.

Results

Study population included 74 patients treated with biologics: 51% female, 73% Crohn’s disease (CD); 37% starting adalimumab, 29% infliximab, 19% ustekinumab and 15% vedolizumab. Prevalence of LTB was 8.1% (6 patients), and all patients underwent isoniazid prophylaxis for 9 months except one patient treated with conventional immunomodulatory therapy which failed prophylactic therapy with both isoniazid and rifampin (liver injury). Among patients with adequate chemoprophylaxis, two patients later on started with anti-TNF therapy (adalimumab), two patients with vedolizumab and one with ustekinumab. One patient with CD and negative LTB screening developed pulmonary TB during induction with infliximab (1 month after initiation); after successful treatment with conventional fourfold therapy, the patient was switched to vedolizumab. During the observational period (median 16 months), all IBD patients with LTB as well with cured TB were in clinical and biochemical remission, without signs of TB (re)activation.

Conclusion

Our study has demonstrated that prevalence of LTB among our IBD patients starting biologics was significant (8.1%). Treatment with vedolizumab, ustekinumab and anti-TNF (adalimumab) after isoniazid chemoprophylaxis appears to be safe during the observational period, without signs of TB reactivation.
P381 Use of ustekinumab in Crohn’s disease: Singapore largest single-centre experience
Authors: Shim H H , Kong S C , Ong W C , Lim T G , Chan P W
Published: January 2020

Background

Ustekinumab is the latest therapeutic option for Crohn’s disease (CD). Efficacy and safety outcomes of its use in the Asia CD population, however, have not been reported.

Methods

Patients with CD who received minimum 14 weeks of UST were included. The primary outcome was the percentage of patients who achieved remission by global physician assessment, GPA [defined by Steroid Free Remission (Harvey Bradshaw Index ≤4 and absence of systemic corticosteroid), stool calprotectin <250 μg/g and CR p < 5mg/l] at baseline, weeks 14, 24 and 54. Secondary outcomes included steroid-free remission, normalisation of CRP (<5mg/l), mucosal healing (absence of mucosal ulceration), transmural healing (absence of disease activity on CT/MR enterography); and adverse events including infection, infusion reaction, malignancy and surgery.

Results

Twenty-two patients were included in this study (Table 1). 22.7%, 50% and 55.6% of patients achieved remission by GPA at weeks 14, 24 and 54 respectively (Table 2). Two (2/5.40%) patients achieved mucosal healing with the median time to scope of 12 (IQR 4.5–15) months. Three (3/7, 42.9%) patients achieved transmural healing with the median time to scan of 8 (IQR 5–11) months. Reported on-treatment infection included pharyngitis, adenovirus, norovirus diarrhoea, dental abscess, shingles and cutaneous Mycobacterium abscessus. Four had surgery during the follow-up. No cases of an infusion reaction or malignancy were reported.

Conclusion

Efficacy and safety profile of ustekinumab in local patients with CD is comparable to their western counterpart in this first real-world Asia cohort.
P382 Application of enhanced recovery after surgery in single-port laparoscopic partial small intestine resection in the treatment of Crohn’s disease
Authors: LI Y , Zhou Z , Yao D , Zheng L , Duan Y , Liu B , Huang Y
Published: January 2020

Background

Single-incision laparoscopic surgery (SILS) with enhanced recovery after surgery (ERAS) can reduce operation trauma and accelerate postoperative rehabilitation. This study aims to investigate the safety and feasibility of SILS with ERAS in the treatment of Crohn’s disease.

Methods

Thirty patients with Crohn’s disease were randomly assigned to receive traditional laparoscopic surgery plus ERAS (n = 20) and SILS plus ERAS (n = 18)，respectively. Comparisons and analysis were made between the two groups in the perioperative conditions.

Results

There were significant differences in the mean operation time between the two groups (p < 0.01)，There were no significant differences in the intra-operative blood loss, postoperative complications rates, the time to first flatus and treatment cost (p > 0.05). There were significant differences in the postoperative hospital stay between the two groups (p < 0.05). WBC, CRP and PCT in SILS plus ERAS group were lower than those in the control group at the first days and the third days after operation, the differences were statistically significant (p < 0.05).

Conclusion

SILS plus ERAS can shorten postoperative hospital stay and facilitate bowel function recovery in the treatment of Crohn’s disease. It is worthwhile to mention the nice cosmetic benefits of SILS, the perioperative SILS plus ERAS program is safe and effective and should be popularised in Crohn’s disease.
P384 Lower infliximab trough levels are associated with higher bowel wall thickness in Crohn’s disease
Authors: Frias Gomes C , Morão B , Neto Nascimento C , Gouveia C , Palmela C , Strecht J , Torres J
Published: January 2020

Background

Therapeutic drug monitoring (TDM) is currently used to optimise anti-TNFα therapy in Crohn’s disease, as higher infliximab trough levels (ITL) are associated with better rates of clinical remission and mucosal healing. Transmural healing is emerging as a potential target in Crohn′s disease, but whether there is any relation with ITL remains unclear. Here, we investigated the relation between ITL with bowel wall thickness (BWT) in patients with CD in maintenance therapy with IFX.

Methods

A retrospective cohort study of CD patients treated with IFX in mono or combination therapy. Patients were included if they had an available ITL during maintenance therapy and available entero-magnetic resonance or computerised tomography performed ±4 months. Transmural inflammation was defined as BWT ≥ 4 mm. Median BWT was measured in the most affected segment. An ROC curve was plotted to determine the best cut-off point of ITL to predict transmural inflammation. Mann–Whitney U-test, logistic regression and Spearman correlation were performed to assess the ITL relation with BWT.

Results

Twenty-nine patients were included (males 55.2%; mean age 39.6 ± 18 years; combo therapy 48.2%). According to the Montreal Classification, most patients were A2 (75.2%), with ileal (L1: 34.5%) or ileocolic disease (L3: 51.7%), and behaviour was: B1 41.4%, B2 24.1%, and B3 34.5%, with concomitant perianal disease in 37.9%. 82.2% were in clinical remission. The median IFX TL was 3.2 μg/ml (IQR 1.15–5.15) and median bowel wall thickness was 7 mm (IQR 4–9). 75.9% of patients had BWT > 4 mm. A BWT > 4 mm was associated with lower clinical remission rates (75% vs. 100%, p = 0.27) and higher C-reactive protein (0.31 vs. 0.14, p = 0.09), albeit not significantly. The area under the curve of ITL for bowel wall thickness was 0.70 (best cut-off value 1.8). Having ITL < 1.8 μg/ml was associated with higher median BWT (8.7 vs. 5.9 mm, p = 0.02) and was a predictive factor for transmural inflammation (OR 1.57, 95% CI [1.08–2.30], p = 0.02). BWT showed a fair correlation with ITL (r = −0.43, p = 0.02).

Conclusion

In our cohort of CD patients treated with infliximab (mono or combo therapy), lower infliximab trough levels were associated with higher bowel wall thickness, reflecting worse transmural inflammation. Proactive TDM could offer a possibility to improve BWT and reduce transmural inflammation.
P427 A hybrid approach of handling missing data in inflammatory bowel disease (IBD) trials: results from VISIBLE 1 and VARSITY
Authors: Chen J , Hunter S , Kisfalvi K , Lirio R A
Published: January 2020

Background

Missing data is common in IBD trials. Depending on the volume and nature of missing data, it can reduce statistical power for detecting treatment difference, introduce potential bias and invalidate conclusions. Non-responder imputation (NRI), where patients (patients) with missing data are considered treatment failures, is widely used to handle missing data for dichotomous efficacy endpoints in IBD trials. However, it does not consider the mechanisms leading to missing data and can potentially underestimate the treatment effect. We proposed a hybrid (HI) approach combining NRI and multiple imputation (MI) as an alternative to NRI in the analyses of two phase 3 trials of vedolizumab (VDZ) in patients with moderate-to-severe UC – VISIBLE 11 and VARSITY2.

Methods

VISIBLE 1 and VARSITY assessed efficacy using dichotomous endpoints based on complete Mayo score. Full methodologies reported previously.1,2 Our proposed HI approach is aimed at imputing missing Mayo scores, instead of imputing the missing dichotomous efficacy endpoint. To assess the impact of dropouts for different missing data mechanisms (categorised as ‘missing not at random [MNAR]’ and ‘missing at random [MAR]’, HI was implemented as a potential sensitivity analysis, where dropouts owing to safety or lack of efficacy were imputed using NRI (assuming MNAR) and other missing data were imputed using MI (assuming MAR). For MI, each component of the Mayo score was imputed via a multivariate stepwise approach using a fully conditional specification ordinal logistic method. Missing baseline scores were imputed using baseline characteristics data. Missing scores from each subsequent visit were imputed using all previous visits in a stepwise fashion. Fifty imputation datasets were computed for each component of Mayo score. The complete Mayo score and relevant efficacy endpoints were derived subsequently. The analysis was performed within each imputed dataset to determine treatment difference, 95% CI and p-value, which were then combined via Rubin’s rules3.

Results

Tables 1 and 2 show a comparison of efficacy in the two studies using the primary NRI analysis vs. the alternative HI approach for handling missing data.

Conclusion

HI and NRI approaches can provide consistent efficacy analyses in IBD trials. The HI approach can serve as a useful sensitivity analysis to assess the impact of dropouts under different missing data mechanisms and evaluate the robustness of efficacy conclusions.

Reference
P446 Transcriptional and microbial biomarkers of response to anti-TL1A therapy in ulcerative colitis: the Phase 2a TUSCANY study
Authors: Hassan-Zahraee M , Ye Z , Xi L , Baniecki M L , Li X , Farin W , Tibaldi L , Allegretti J R , Romatowski J , Scherl E J , Klopocka M , Hyde C , Danese S , Longman R , Hung K E
Published: January 2020

Background

Tumour necrosis factor α-like ligand 1A (TL1A) acts as a synergistic cytokine that amplifies pro-inflammatory signals to increase T-cell, natural killer (NK) cell, and innate lymphoid cell production of cytokines, which are thought to be key drivers of inflammatory bowel disease (IBD) and intestinal fibrosis. The recent Phase 2a TUSCANY study demonstrated the efficacy of PF-06480605, a fully human immunoglobulin G1 monoclonal antibody targeting TL1A, in the treatment of participants with moderate to severe active Ulcerative Colitis (UC). Here, we present transcriptomic analysis of intestinal tissue biopsies and metagenomic analysis of the faecal microbiome to further evaluate the treatment effect of PF-06480605.

Methods

The Phase 2a, open-label, multicentre, single-arm TUSCANY study (NCT02840721) evaluated the safety, tolerability and efficacy of PF-06480605 in participants with moderate to severe UC. Participants received 500 mg intravenous (IV) PF-06480605 every 2 weeks (Q2W) for a total of 7 doses, with a 14-week follow-up period. We performed RNA sequencing of colonic biopsies and metagenomic sequencing (>40 million reads per sample) of faecal samples taken prior to and after 12 weeks of therapy. Differential expression and cell subset deconvolution by CytoReason were used to identify genes and immune cells involved in response to therapy. Differential abundance analyses based on taxonomic profiling was performed using the GOTTCHA metagenome mapping algorithm to discover whether microbial taxa changed in response to treatment.

Results

Tissue transcriptomic analysis identified a robust inhibition of adaptive (Th1, Th2 and Th17) and innate (macrophage) inflammatory pathways known to be associated with UC pathogenesis and a significant reduction in fibrosis-associated pathways (MMP3, MMP7 and MMP10). Transcriptomic responses were most pronounced in participants achieving endoscopic improvement (Mayo endoscopic subscore of ≤1). A candidate baseline gene signature was predictive of endoscopic improvement (area under the curve [AUC] 0.75; p-value = 0.03). Metagenomic analysis revealed a significant reduction in inflammatory pathobiont species (S. salivarius, S. parasanguinis, and H. parainfluenzae) following treatment.

Conclusion

These results provide insight into the molecular and microbial mechanisms underlying the efficacy of anti-TL1A therapy for UC. We defined a baseline transcriptomic signature to predict response and a pathobiont treatment signature. These findings may enable the development of precision medicine strategies for anti-TL1A therapy in the treatment of intestinal inflammation.