bluuebunny/crossref_metadata_2025 huggingface dataset:
P693 Development and evaluation of i-TRACKER infliximab and i-TRACKER anti-Infliximab kits: fast and innovative chemiluminescent assays for the monitoring of patients treated with infliximab
Authors: Noguier G , Montaillier C , Daviere S , Colombeau L , Parussini E
Published: January 2020

Background

Infliximab, a monoclonal antibody directed against TNFα, is a drug widely used for the treatment of inflammatory diseases (rheumatoid arthritis, Crohn’s disease, etc.). Therapeutic drug monitoring is currently proposed to provide useful information to clinicians to improve the efficacy of the treatment. Theradiag has just developed the innovative i-TRACKER Infliximab and i-TRACKER Anti-Infliximab kits: fast quantifications of Infliximab and Anti-Infliximab antibodies fully automated on the random access i-TRACK10 chemiluminescent analyser.

Methods

Analytical performances were assessed using two types of serum samples: human serum spiked with Infliximab or Anti-Infliximab antibodies, and samples from inflammatory bowel disease patients treated with Infliximab (n = 41). On one hand, Infliximab from serum sample was captured by TNFα coupled magnetic microparticles and Anti-Infliximab polyclonal antibodies conjugated to acridinium ester were used for the detection of Infliximab. On the other hand, Anti-Infliximab antibodies were captured according to Infliximab coupled magnetic microparticles and detected with the use of Infliximab conjugated to acridinium ester. Light emission was linked to the quantity of Infliximab, or anti-Infliximab antibodies, presents in the sample.

Results

Infliximab measurement showed high accuracy (recovery was comprised between 80% and 107%). High precisions were reached for both assays (intra-precision CV were below 8.1% and 2.7% for Infliximab and Anti-Infliximab assays; inter-precision CV were below 11.7% and 4.8% for Infliximab and Anti-Infliximab assays) and no interferences were seen with biologic agents (bilirubin, haemoglobin, lipids, biotin and rheumatoid factors). The dynamic ranges of the assays were 0.3–24 µg/ml for Infliximab quantification and 10–2000 ng/ml for Anti-Infliximab antibodies quantification. i-TRACKER Infliximab and i-TRACKER anti-Infliximab assays were compared with respective LISA-TRACKER assays and showed excellent correlation (R² = 0.94, Slope = 1.04 for Infliximab assay; Spearman’s coefficient correlation was 0.98 for Anti-Infliximab assay).

Conclusion

i-TRACKER kits are innovative assays which exhibit fast (time to results <40 min), accurate (standardised with NIBSC/WHO international standard Infliximab) and reproducible results for the quantification of princeps and biosimilar molecules (CT-P13, SB2). Excellent agreements were observed with respective LISA-TRACKER assays. i-TRACKER kits are valuable tools for the monitoring of patients treated with Infliximab.
P697 Efficacy and safety of ustekinumab in Crohn’s disease: A real-world study from Australia
Authors: Kakkadasam Ramaswamy P , Moattar H , Sawyer E , Edwards J , Shukla D
Published: January 2020

Background

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved in Australia for the treatment of adults with moderate to severe Crohn’s disease (CD) in 2017. The aim of this retrospective single centre study was to study the efficacy and safety of UST in CD in a real world cohort.

Methods

Patients with CD who began UST therapy between June 2017 and July 2019 were included. UST induction was given as an infusion (6 mg/kg) at week 0 followed by 90 mg subcutaneous injection (SC) at week 8 and 90 mg SC every 8 weeks as maintenance. Primary endpoint (PE) was steroid free clinical remission or steroid free clinical response at week 24. Secondary endpoints (SE) were: endoscopic response or remission, radiological response or remission, biochemical response (CRP < 5 mg/L or Calprotectin <150 μg/g), clinical response or remission at week 52.

Results

Seventy-six patients with CD were included in the study. 64.5% failed ≥1 anti-TNF and 13.1% failed anti-TNF and vedolizumab; 26(34.2%) patients were biologic-naïve. Median follow-up was 61 weeks. Ten patients (13.1%) discontinued UST, and the median time to discontinuation was 48 weeks; eight patients due to loss of response, one patient due to paradoxical worsening of arthralgia, one patient chose to stop treatment. Six patients underwent surgery whilst on UST. At week 12, 48 (63.1%) of patients achieved steroid free clinical remission or response [19/26 (73%) Anti-TNF naive and 29/49 (59%) anti-TNF exposed]; of these patients, 16/19 (84%) in the anti-TNF naive group and 19/29(65.5%) in the anti-TNF exposed group achieved PE. Forty-seven (61.8%) patients achieved PE. At 52 weeks, 68.2% (30/44), 67.5% (27/40), 56.1% (23/41), 69% (29/42) achieved endoscopic, radiological, biochemical and clinical endpoints respectively. Achieving steroid free clinical response or remission at week 12 was associated with achieving PE (79% vs. 42.8%, OR 3.6, p 0.01) and clinical SE (83.3 vs. 58.3%, p 0.001). Patients with B2/3 vs. B1(54% vs. 82%, p 0.09), ≥2 biological failure (72% vs. 33%, p 0.09), CRP < 6 baseline (55 % vs. 67.5%, p 0.3) were less likely to attain PE.

Conclusion

In a real-world cohort, UST appears efficacious and safe in medium and long term, with modest clinical, biochemical, radiological and endoscopic outcomes. Patients who achieve steroid-free clinical remission or response at 12 weeks are more likely to be in clinical remission or response at 24 and 52 weeks.
P706 Adalimumab drug levels at secondary loss of response in Crohn’s disease; are we aiming high enough? A retrospective, international multi-centre study
Authors: Swaine A , Reynolds R , Roblin X , Gibson D , Martin C , Irving P , Sparrow M , Ward M
Published: January 2020

Background

Evidence supporting therapeutic drug monitoring with adalimumab (ADA) in Crohn’s disease (CD) is not as strong as for infliximab. Data examining whether changes in ADA drug exposure after dose intensification are associated with outcomes are lacking. We aimed to explore associations between ADA drug level exposure at loss of response and then at 6 and 12 months and compare these to short term clinical outcomes.

Methods

Retrospective study of adult CD patients who underwent ADA intensification to weekly dosing for secondary loss of response at three tertiary centres between 2013 and 2018. We compared trough ADA drug levels using a drug sensitive ELISA at loss of response and at 6 and 12 months after intensification with paired rates of clinical remission (Harvey Bradshaw Index <5 or Crohn’s Disease Activity Index <150), biochemical remission (C-reactive protein <5 mg/L), objective remission (CRP < 5 mg/L, faecal calprotectin < 150 µg/g or absence of inflammation at endoscopy or imaging) and ADA failure (based on Physicians Global Assessment. We performed comparisons between continuous and categorical data using Fischer’s exact or Mann–Whitney test. A receiver operated curve (ROC) analysis was used to identify target ADA levels associated with outcomes of interest.

Results

In total, 133 CD patients were included; median disease duration 8 years (IQR 4–17), 51% were biologic-exposed and 49% received concomitant immunomodulation. Rates of clinical remission, objective remission and ADA failure were 73.0%, 37.4% and 25.0% at 6 months and 65.8%, 34.0% and 42.8% at 12 months, respectively. Drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders; however increases in drug levels at 6 and 12 months were associated with improved outcomes at these time points (Figure 1). ROC analysis demonstrated that ADA drug levels 6 months after intensification > 8.9, 9.6 and 8.9 µg/ml were associated with clinical remission, objective remission and ADA non-failure respectively. Similar results were demonstrated with ADA drug levels at 12 months after dose intensification (Figure 1).

Conclusion

ADA drug levels at loss of response are not associated with subsequent 6 or 12 month outcomes. However, measurement of subsequent ADA drug levels at 6 and 12 months post escalation demonstrates that higher levels (with a target threshold between 7.7–10.9μg/ml) were associated with favourable outcomes. This study suggests that performing TDM subsequent to dose escalation of ADA has a role in predicting outcomes. Further, prospective studies dosing to target ADA drug levels are therefore needed.
P723 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: Results from the GO-LEVEL study
Authors: Samaan M , Cunningham G , Tamilarasan G , Rawstron K , Hawash K , Beltran L , Ray S , Mawdsley J , Anderson S , Sanderson J , Arkir Z , Irving P
Published: January 2020

Background

The exposure–response relationship associated with the use of golimumab for UC has been previously demonstrated in the PURSUIT trial programme. A significant association between serum golimumab concentrations (SGC) and favourable outcomes was observed during both induction and maintenance therapy. However, data regarding the optimal therapeutic SGC threshold is limited.

Methods

GO-LEVEL was an open-label, phase IV, investigator initiated study (NCT03124121) which included a prospective cohort of UC patients commencing golimumab induction therapy, as well as a cross-sectional cohort receiving maintenance treatment (>18 weeks from initiation).

Patients commencing induction therapy all had disease activity objectively confirmed and were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare, or during stable remission. Clinical disease activity was evaluated using SCCAI and PRO2, and biochemical activity using FC and CRP. Combined clinical-biochemical remission was defined as SCCAI<3 as well as FC<250ug/g. SGC and anti-golimumab antibodies (AGA) were measured using a drug-sensitive ELISA (LISATRACKER, Theradiag). Fishers exact or Mann–Whitney U were used to compare groups, ROC analysis to identify therapeutic thresholds and Spearman’s rank coefficient (rs) for correlations.

Results

Thirty-nine patients were included in the induction cohort, of whom 15 (38%) achieved combined remission at week 6. The median SGC of those in combined remission was significantly higher than those who were not (5.0 vs. 3.1 μg/ml, respectively, p = 0.03). ROC curve analysis demonstrates 3.8 μg/ml as the optimal therapeutic threshold to achieve combined remission at week 6 (sensitivity 0.71, specificity 0.65, AUC 0.72). Significant, inverse correlations were also observed between week 6 SGC and PRO2, CRP and FC (rs −0.41 (p = 0.01), −0.47 (p = 0.004) and −0.40 (p = 0.02), respectively). However, week 6 SGC did not predict outcomes at week 10 or 14.

Sixty-four patients were included in the maintenance cohort; 32 (50%) were in combined remission, 32 were not. The median SGC of those in combined remission was significantly higher (3.0 vs. 2.1 μg/ml, respectively, p = 0.003). ROC curve analysis demonstrates 2.4 μg/ml as the optimal therapeutic threshold to achieve combined remission (sensitivity 0.73, specificity 0.66, AUC 0.71).

No AGA were detected in either cohort.

Conclusion

GO-LEVEL offers further evidence of the exposure-response relationship with golimumab. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested SGC therapeutic thresholds of 3.8 μg/ml at week 6 and 2.4 μg/ml during maintenance.
P730 Effectiveness and safety of endoscopic balloon dilation of colorectal strictures in Crohn’s disease
Authors: TILMANT M , serrero M , Poullenot F , Bouguen G , Pariente B , Altwegg R , Basile P , Filippi J , Vanelslander P , Buisson A , Vuitton L , Desjeux A , Laharie D , Le Balch E , Nachury M , Boivineau L , Savoye G , Hebuterne X , Poincloux L , Lamrani A , Fumery M
Published: January 2020

Background

Endoscopic balloon dilation (EBD) is widely used to manage Crohn’s disease (CD) ileal stricture. However, data of EBD on inflammatory bowel diseases (IBD) colorectal strictures are scarce.

Methods

We performed a retrospective study in 9 tertiary centres, including all consecutive IBD patients who underwent EBD for native or anastomotic colorectal stricture between 1999 and 2018. Outcomes were rate of technical success defined by a passable stricture at the end of the EBD, clinical success defined by a passable and asymptomatic stricture and colonic resection at the end of follow-up. Factors associated with EBD success were also investigated by logistic regression.

Results

Fifty-seven patients (25 women, median age: 36 years, InterQuartile Range, 31–48) were included. All patients had CD and 42 (74%) had symptomatic stricture. Regarding the 60 strictures, 52 (87%) were native and the most frequent location was left colon (27%). 39 (65%) measured less than 5 cm, 57 (95%) were non-passable by the scope and 35 (58%) ulcerated. Among the 161 EBD performed (median number of dilatations per strictures: 1, IQR 1–3), technical success was observed in 123 (76%) EBD. One perforation occurred (0.6% per EDB and 2% per patient). After a median follow-up of 4.3 years [IQR 2.0–8.4], 24 patients (42%) underwent colonic resection, 9 (16%) had symptomatic strictures non-passable by the scope, 11 (19%) had asymptomatic non-passable strictures and 13 (23%) had asymptomatic strictures passable by the scope. One colon lymphoma and one colorectal cancer were diagnosed (3.5% of patients), respectively on endoscopic biopsies and at the time of surgery. None factor was associated with technical, clinical success, or surgery including therapeutic modification.

Conclusion

EBD of CD-associated colorectal strictures is feasible, efficient and safe as more than 50% of patients avoid surgery.
P736 Utility of infliximab serum concentration in inflammatory bowel disease treatment in real world practice at Hospital Universitario de Canarias
Authors: Carrillo Palau M , Alonso-Abreu I , Ramos-Lopez L , Fernando G N , Hernandez Alvarez-Buylla N , Hernandez-Perez A , Medina-Chico S , Quintero E
Published: January 2020

Background

Anti-TNF drugs are effective treatments for the management of inflammatory bowel disease (IBD) but treatment failure is common. The aim of this study was to investigate the association between inflammatory biomarkers, serum concentrations of IFX and antiIFX antibody concentration during induction and maintenance treatment and to investigate the association with disease activity and response to treatment in our patients from 2017 to 2019.

Methods

Retrospective observational study. We enrolled patients receiving IFX from March 2017 until March 2019. Demographic data, disease characteristics, previous medical treatments and surgeries were recorded. Clinical Activity Index (Harvey Index and Parcial Mayo Score) and CRP, faecal calprotectine (FC) and endoscopy or radiological activity were recorded at baseline, and at 6, 12 and 24 months of treatment. IFX serum concentrations and anti-IFX antibody concentration were measured at the end of induction (week 8) and during follow-up (6, 12 and 24 months).

Results

One hundred and eighty-one IBD patients were treated during the study period, and 175 patients were included: 128 (73.1%) Crohn’s disease (CD), 46 (26.3%) ulcerative colitis (UC) and 1 (0.6%) indeterminated colitis (IC). 95 male, 85 female, mean age 45 years (±15); 93% were naive to IFX. 73.6% started IFX combined with inmunomodulator treatment. At week 0, 80% had an active disease (Global Physician Assessment), 58.8% had CRP >5 μg/dl and 62% had FC > 150 mg/kg. At 12 months, 126 patients continued under IFX, and 68% had an stable disease and 44% were intensified. Thirty-six per cent had CRP > 5 μg/dl and 37% FC>150 mg/kg. At 24 months, 90 patients continued with IFX, from which 80% were stable and 43% were intensified.38% had CRP >5 μg/dl and 26% FC >150 mg/kg. Patients with post-induction (week 8) serum IFX concentration >7 μg/ml had more stable disease (p: 0.04) at that moment and IFX serum concentration > 3 μg/ml at 18 months was corelationated with no inflammation at endoscopy or radiology (p: 0.025). In the multivariate analysis stenosant phenotype and CRP < 5 mg/dl at 6 months were relationated with early stop of IFX treatment (<1 year).

Conclusion

Our study shows that IFX levels >7 μg/ml correlates with a better clinical response. Disease phenotype and inflammatory parameters could influence in long time maintenance treatment. Drug-level monitoring and measurement of baseline inflammatory parameters may improve the management of IBD.
P746 Prevalence, features and outcomes of splachnic vein thrombosis in inflammatory bowel disease. A nationwide, retrospective study from the ENEIDA registry
Authors: Masnou H , Mañosa M , Menchén L , Mesonero F , Bujanda L , Castro J , Gonzalez-Partida I , De Francisco R , García-Alonso F J , García M J , González-Muñoza C , Huguet J M , Iborra M , Cano-Sanz N , Domènech Moral E
Published: January 2020

Background

The risk of splanic vein thrombosis (SVT) -as defined as that involving the portal vein and/or its intrahepatic branches, mesenteric, splenic and/or suprahepatic veïns is mainly observed, among others, in inflammatory abdominal conditions. Thromboembolic complications are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, characteristics, risk factors and evolution of SVT in patients with IBD. Our aims were to describe the characteristics of SVT in patients with IBD, diagnostic explorations, treatment and evolution.

Methods

Retrospective, multicentre, descriptive study of the ENEIDA registry with a diagnosis of SVT. In addition to epidemiological and clinical features of IBD, we recorded specifically diagnosis, treatment, disease activity at the time of SVT and outcome of SVT.

Results

Over 59,000 IBD patients in the ENEIDA registry, only 49 episodes of SVT were identified (35 Crohn’s / 14 Ulcerative Colitis); 69% men, median age 42 years old, 35% smokers. 37% had a past history of surgery and/or abdominal inflammatory conditions, 16% extra-intestinal neoplasia, 23% baseline immune or hematologic conditions and 14% liver disease. Finally, 16% had a previous episode of venous thrombosis. The most frequent forms of clinical presentation were abdominal pain with/without fever (59%), and radiological findings in the setting of active IBD (25%). ST coincided with IBD activity in 76% of cases. The diagnosis of SVT was based in the findings of an abdominal CT in 82%. The most frequent localition of SVT were intrahepatic portal branches (51%) and superior mesenteric vein (47%). Only 47% had a basic aetiological study, and 37% underwent gastroscopy (median 7 months from the diagnosis of SVT) showing oesophageal varices in 67%. Anticoagulation therapy was prescribed in 94% of the episodes (74% within the first month since diagnosis), for a median of 7 months. In 90% of the cases, there was a further radiological assessment, 61% of which showing the resolution of the SVT (median of 5 months from the beginning anticoagulation treatment).

Conclusion

SVT seems to be a rare (or underdiagnosed) complication in IBD patients, it is mostly associated with disease activity and evolves suitably when anticoagulation therapy is suitably started.
P769 Prevalence and duration of gastrointestinal symptoms in the 10 years before diagnosis of inflammatory bowel disease: A national cohort study
Authors: Blackwell J , Saxena S , Jayasooriya N , Petersen I , Hotopf M , Bottle A , Pollok R
Published: January 2020

Background

Gastrointestinal (GI) symptoms of Inflammatory Bowel Disease (IBD) may go undiagnosed resulting in diagnostic delay.

Aims: To determine the frequency and duration of GI symptoms in the decade before the diagnosis of Crohn’s Disease (CD) and ulcerative colitis (UC) and risk factors for delayed specialist review.

Methods

We used the Clinical Practice Research Datalink, a nationally representative research database, to identify incident cases of CD and UC diagnosed from 1998 to 2016. Comparison cohorts without IBD were matched 4:1 for age and sex and assigned the IBD diagnosis date of their matched IBD patient as a pseudo-diagnosis date. We compared the prevalence of GI symptoms between the IBD and comparison cohorts in the 10 years before IBD diagnosis. We identified individuals with chronic GI symptoms lasting more than 6 weeks and measured their time to receiving a specialist review with a gastroenterologist, paediatric gastroenterologist or colorectal surgeon. We identified risk factors for receiving specialist review after presenting with chronic GI symptoms.

Results

We identified 5874 incident cases of CD, 13,681 incident cases of UC and comparison cohorts of 78,114 individuals. 10% of the CD and UC cohorts reported GI symptoms to their primary care physician 5 years before diagnosis.

Fewer than 50% of patients were reviewed by a specialist within 18 months of presenting to their primary care physician with chronic GI symptoms. Patients with a previous diagnosis of Irritable Bowel Syndrome (IBS) or depression were less likely to receive timely specialist review (IBS: HR 0.77, 95%CI 0.60–0.99, depression: HR 0.77, 95%CI 0.60–0.98).

Conclusion

A substantial number of individuals experience GI symptoms many years before receiving a diagnosis of IBD. IBS and depression are risk factors for delayed specialist review. Rapid diagnostic pathways should be established to reduce the burden of diagnostic delay in IBD.
P770 Ascertainment of pediatric inflammatory bowel disease cases from administrative health data in Québec, Canada
Authors: Jantchou P , Conus F , Richard H , Rousseau M C
Published: January 2020

Background

Administrative databases are useful for estimating population-level disease occurrence. Our objective was to ascertain cases of pediatric inflammatory bowel disease (IBD) by applying two validated algorithms to administrative health data, evaluate agreement, and compare health services utilisation between concordant and discordant cases.

Methods

The Quebec Birth Cohort on Immunity Health was established through linkage of administrative databases and includes 400 611 persons born in the province of Québec (Canada) from 1970 to 1974. Physician consultations (PC) and hospitalisations (H) for IBD were documented in health databases until 2014. Two validated algorithms were used to identify pediatric IBD cases. Firstly, a single-step algorithm was applied [5PC or 2H within 4 years]. Secondly, a two-step algorithm was implemented, first considering whether the person had undergone sigmoidoscopy/colonoscopy before age 18 [yes: 4PC or 2H within 3 years; no: 7PC or 3H within 3 years]. We evaluated the agreement between both algorithms using the Kappa statistic, and compared health services utilisation among concordant and discordant cases using a t-test.

Results

The single-step algorithm generated 527 pediatric IBD cases (0.13%), whereas 480 (0.12%) were identified with the multi-step algorithm. Among the 534 cases identified by either algorithm, 473 (88.6%) were identified by both, 54 (10.1%) only by the single-step, and 7 (1.3%) only by the multi-step algorithm. Kappa was 0.94 (95% confidence interval: 0.92, 0.95), and the proportions of positive and negative agreement were respectively 0.94 and 1.00. The average number of PC and H before age 18 years among concordant and discordant cases was respectively 26.0 and 3.9 (p < 0.0001).

Conclusion

The prevalence of pediatric IBD was similar when applying two different case identification algorithms, few cases were discordant. In the near future, a survey conducted in a subset of the cohort will allow us to compare self-report with ascertainment from administrative databases.
P783 Non-alcoholic fatty liver disease and advanced liver disease in patients with inflammatory bowel disease: prevalence and risk factors
Authors: Demir M
Published: January 2020

Background

Increased occurrence of non-alcoholic fatty liver disease NAFLD is observed in patients with IBD. The aim of this study was to assess the prevalence and risk factors of NAFLD and associated advance liver fibrosis in patients with IBD

Methods

This is a retrospective study. Between January 2010 and August 2019, patients with Crohn’s disease/ulcerative colitis who admitted to our Gastroenterology Unit were included in the study. Hepatic steatosis was assessed by abdominal ultrasound. The diagnosis of advanced fibrosis was evaluated with non-invasive FIB 4 score and FIB-4>3.25 was considered an advanced liver disease. Patients with a history of excessive alcohol or recent steroid use, chronic viral hepatitis and other chronic liver diseases were excluded. Univariate and multivariate analysis were performed.

Results

Five hundred and thirty-nine, 52% male, mean age 44 ± 18 years, were enrolled. Among 539 IBD patients, 322 (59.7%) in ulcerative colitis patients vs. 217 (41.3%) in Crohn’s disease patients were diagnosed. The sonographic prevalence of NAFLD was 32% (172/539) and advanced liver disease was found in 12% (21/172) in IBD patients with NAFLD. Univariate analysis showed that >40 years old (p = 0.034), ≥25 Body Mass Index (BMI)(p < 0.001), presence of metabolic syndrome(p < 0.001) and type 2 diabetes(p < 0.001), ≥5 years of duration of disease (p < 0.001), biological agents and/or azothiopurine use in the past (p < 0.001), ≥126mg/dl fasting plasma glucose (p = 0.04), elevated alanine aminotransferase (ALT) (p < 0.001), ≥240mg/dl total cholesterol (p = 0.021), ≥150mg/dl triglyceride (p = 0.038) and hyperuricemia (p = 0.019) were risk factors for NAFLD in patients with IBD. According to the multivariate analysis presence of metabolic syndrome and type 2 diabetes, ≥5 years of duration of disease and elevated ALT were an independent predictive factor of NAFLD (respectively, p < 0.003, p = 0.002, p < 0.001, p < 0.001). Univariate analysis showed that >40 years old (p = 0.037), the presence of metabolic syndrome (p < 0.001), type 2 diabetes (p < 0.001) and Crohn’s disease (p = 0.012), history of surgery (p = 0.003), ≥5 years of duration of disease (p < 0.001), elevated ALT (p < 0.001) and <3 mg/dl albumin (p = 0.038) were risk factors for advanced liver disease in IBD patients with NAFLD. According to the multivariate analysis, the presence of type 2 diabetes and ≥5 years of duration of disease was an independent predictive factor of advanced liver disease in IBD patients with NAFLD (respectively, p < 0.001, p < 0.001).

Conclusion

NAFLD is a very common disease in patients with IBD. NAFLD is not rare cause of advanced liver disease in patients with IBD. Type 2 diabetes and ≥5 years of duration of disease were an independent predictive factor of advanced liver disease in IBD patients with NAFLD.
P790 Dental caries occurrence among patients with inflammatory bowel disease (IBD)
Authors: Piątek D , Jarmakiewicz-Czaja S , Korona-Głowniak I , Malm A , Sztembis J , Filip R
Published: January 2020

Background

Inflammatory bowel disease (IBD), including patients’ diet, way of treatment and general health may have an impact on teeth condition. Due to multifactorial nature of caries that its linked to susceptibility of hard tooth tissues, cariogenic microorganisms and presence of fermentable carbohydrates, the course of disease can be modified at many levels. The aim of the study was to assess dental caries experience in adult patients with Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

The study involved 224 individuals: 98 with diagnosed CD, 75 with UC and 51 of control group (CG) with mean age 34.7. The complete assessment of the hard tooth tissues based on the DMFT index (decayed D, missing M, filled F teeth) was performed.

Results

There were no statistically significant differences between the examined groups in terms of DMFT index values, however, a statistically significant difference was found in the number of teeth with caries (D) (mean 3.99, 3.05 and 1.96 for CD, UC and CG respectively; H=13.55 p < 0.05). All groups had higher mean D values in men than women, and achieved the highest mean value in CD group (4.78) compared with UC (3.68) and healthy controls (2.06)(H=8.71 p < 0.05). The results of D values for CG obtained in our study confirm the literature data for healthy population aged 35–44 in Poland (mean D~2). The number of lost teeth (M) in the studied population was high and amounted to 5.47, 5.25 and 3.94 for the examined groups, respectively. A thorough analysis showed that in the group of men the difference in the M value was statistically significant at 5.83, 5.94 and 1.11 for CD, UC and CG respectively (H=15.84 p < 0.05). Statistically significant differences (H=6.21 p < 0.05) were observed in the number of filled teeth (F), without secondary caries, which highest value was recorded in CG (10.76) and the lowest in the CD group (8.93).

Conclusion

The highest D and M values were observed in patients with CD, especially in men, which proves the intensity and activity of dental caries disease in this group.
P794 Nutritional assessment in inflammatory bowel disease (IBD): development of the Groningen IBD Nutritional Questionnaires (GINQ)
Authors: Peters V , Alizadeh B , de Vries J , Dijkstra G , Campmans-Kuijpers M
Published: January 2020

Background

Diet plays a key role in the complex aetiology and treatment of inflammatory bowel disease (IBD). Most existing nutritional assessment tools neglect intakes of important foods consumed or omitted specifically by IBD patients or incorporate non-Western dietary habits, making development of appropriate dietary guidelines for (Western) IBD patients difficult. Hence, we developed a food frequency questionnaire (FFQ), the Groningen IBD Nutritional Questionnaires (GINQ-FFQ); suitable to assess dietary intake in IBD patients.

Methods

To develop the GINQ-FFQ multiple steps (Figure 1) were taken; identification of IBD specific foods, literature search and evaluation of current dietary assessment methods. Expert views were collected and in collaboration with Wageningen University, division of Human Nutrition and Health, this semi-quantitative FFQ was developed using standard methods to obtain a validate questionnaire. Next, the GINQ-FFQ was digitalised into a secure web-based environment which also embeds additional nutritional and IBD-related questions.

Results

The GINQ-FFQ is an online self-administered FFQ evaluating dietary intake over the past month as a proxy of habitual intake of the previous six months. The GINQ-FFQ consists of 121 questions on 218 food items. It takes about 45 min to fill out the GINQ-FFQ.

Conclusion

This paper describes the design process of the GINQ-FFQ which is newly developed to assess dietary intakes especially (but not exclusively) in IBD patients.
P798 Societal costs attributable to Crohn’s disease and ulcerative colitis within the first 5 years after diagnosis: –a Danish Nationwide Cost-of-Illness Study 2003–2015
Authors: ALULIS S , Vadstrup K , Borsi A , Elkjær Stallknecht S , Olsen J , Rikke Jørgensen T , Wennerström C , Qvist N , Munkholm P
Published: January 2020

Background

There is little information on cost-of-illness among patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) in Denmark. The objective of this study was to estimate the average 5-year societal costs attributable to CD or UC including costs related to health care, prescription medicine, home care, and production loss.

Methods

Incident patients with CD or UC were identified in the National Patient Registry and matched with a non-IBD control from the general population on age and sex. Attributable costs were estimated applying a difference-in-difference approach, where the total costs among individuals in the control group were subtracted from the total costs among patients. Information on primary and secondary healthcare services were obtained from the National Health Insurance Service Registry.

Results

CD and UC incidence was approximately 14 and 31 per 100,000 persons-years, respectively. Average attributable costs were highest the first year after diagnosis, with costs equalling €12,919 per CD patient and €6,501 per UC patient. Hospital admission costs accounted for 36% in the CD population and 31% in the UC population, the first year after diagnosis. Production loss exceeded all other costs the third year after diagnosis.

Conclusion

We found that the societal costs attributable to incident CD and UC patients are substantial compared with the general population, primarily consisting of hospital admission costs and production loss. Appropriate treatment at the right time may be beneficial from a societal perspective.
P806 Increasing incidence of microscopic colitis in a population-based cohort study in a French speaking region of Switzerland
Authors: Maye H , Ekaterina S , Schoepfer A
Published: January 2020

Background

Microscopic colitis (MC) is a chronic inflammatory disease of the colon presenting with watery diarrhoea. It encompasses two entities, namely lymphocytic colitis (LC) and collagenous colitis (CC). Population-based epidemiologic data the frequency and natural history of microscopic colitis are scarce. We evaluated the clinical presentation at diagnosis, incidence and prevalence of MC in Cantons of Vaud and Fribourg, Switzerland.

Methods

Cantons of Vaud and Fribourg lie in the French-speaking, Western part of Switzerland. As of 12/2017, both cantons together had a population of 1,109,230 inhabitants. We contacted all Pathology institutes (n = 6) in both cantons in order to identify patients that have been diagnosed with microscopic colitis. We then performed a chart review in all adult and paediatric gastroenterology practices in order to identify MC patients and to assess the incidence, prevalence, their clinical, endoscopic, and histological characteristics as well as natural history.

Results

Out of 252 patients, a total of 218 fulfilled the diagnostic criteria for MC, whereof 123 had LC and 95 had CC. Age at first diagnosis of MC was 63.2 ± 14.3 years (62.8 ± 14.3 for LC, 63.7 ± 14.4 years) and median diagnostic delay was 1.1 ± 3.1 years. Symptoms leading to MC diagnosis were diarrhoea (100%), abdominal pain (31.7%), weight loss (31.2%), bloating (20.6%), fatigue (9.6%), and nausea/vomiting (3.2%). The following risk factors were found in MC patients: statins (27.1%), aspirine (23.4%), proton pump inhibitors (22.5%), serotonine reuptake inhibitors (22.5%), smoking (20.2%), non steroidal anti-inflammatory drugs (14.2%), and neuroleptics (4.1%). Median exposure time to risk factors was 55 months (IQR 33–78, range 1–280 months). Associated auto-immune diseases (celiac disease, type 1 diabetes, autoimmune gastritis, autoimmune thyroiditis, rheumatoid arthritis) were found in 14 patients (6.4%). No patient was diagnosed with MC prior to 1994. Incidence of MC significantly increased from 0.36/100,000 inhabitants in 1994–1997 to 6.85/100,000 inhabitants in 2017 (p = 0.025). The cumulative prevalence of MC, LC, and CC in 2017 was 19.65/100,000, 11.09/100,000, and 8.56/100,000, respectively.

Conclusion

The incidence and cumulative prevalence of MC shows a steady increase in an indicator region of roughly 1 million inhabitants in French speaking part of Switzerland.
P813 Inflammatory bowel disease in older patients: experience at a single centre
Authors: Diaz Alcazar M M , Martinez Tirado P , Vidal Vilchez B , Zuñiga de Mora Figueroa B
Published: January 2020

Background

The characteristics of inflammatory Bowel Disease (IBD) seem different according to the age of the patient at diagnosis. Moreover, age influences the evolution of the disease. The aim of the study was to know the prevalence of IBD in patients older than 65 years old and the evolution of the disease at this age.

Methods

Retrospective descriptive study. Database from patients of the Hospital Universitario San Cecilio of Granada (Spain). 50 patients with 65 years old or more and 50 under this age have been randomly selected. Their electronic clinical records have been reviewed.

Results

The IBD Unit in our Hospital serves 1218 people with this disease, of whom 212 are elderly patients (17.4%). In the serie of 100 randomly selected patients, mean age is 58.42 years. The disease began before 65 years old in 74% of elderly patients.

All the elderly patients continue follow-up, while 4 (8%) of the younger patients dropped out the follow-up in the IBD Unit. With regard to hospital admissions, 27 elderly patients (54%) have never required hospitalisation compared with 18 (36%) aged under 65 years. Corticosteroids were used at diagnosis in 27 (54%) of older vs. 28 (56%) of the younger patients. Meanwhile, topical treatment is used by 33 (66%) of older vs. 22 (44%) of the younger ones. The current treatment is summarised in Figure 1.

Conclusion

(1) The prevalence of IBD is increasing. IBD in older patients is also escalating due to the low mortality of the disease and the increase of patients with late-onset. In our serie, the prevalence in elderly patients is 17.4%. (2) UC is more frequent in older patients than in younger ones (70% vs. 42%). With regard to CD, penetrating disease is less frequent in older patients but stricturing pattern is more prevalent. (3) Adherence to follow-up in elderly patients is higher and they need fewer hospital admissions than younger patients. (4) In our serie, surgical and biological treatments are less frequent in elderly patients. Moreover, there are more patients above 65 years that do not take maintenance treatment or they only take mesalamine. (5) Chronological age is different from biological age. Older patients with a good quality of life should not be excluded from new treatments or clinical trials due to age. More evidence about older patients is needed to improve de diagnosis, the knowledge about the evolution and define better the treatment in this group of age.
P825 The impact of a SNP-dose–response effect on course of inflammatory bowel disease: a numerical analysis of SNP distribution within the Swiss IBD Cohort Study
Authors: Biedermann L , Denoth L , Rossel J B , Butter M , Vavricka S , Misselwitz B , Greuter T , Schreiner P , Cleynen I , Rogler G , Scharl M
Published: January 2020

Background

Several large genome wide association studies have identified an increasing number of IBD risk loci with currently more than 240 established loci and generated robust data on disease association. However, knowledge remains limited on distinctive associations to specific clinical characteristics. The Swiss IBD Cohort Study (SIBDCS) represents a large prospective cohort study with clinically and phenotypically sound data collection since 2006 including genotyping. In this study, we aimed to determine individual associations of known risk loci with clinical features of patients in the SIBDCS, as well as their combined effect on clinical outcomes.

Methods

Based on 158 analysed SNPs, we investigated the numerical distribution of risk alleles and determined an individual SNP risk score (defined as percentage of risk alleles; i.e. number of risk alleles divided by twice the number of given SNPs multiplied with 100). We then performed linear regression modelling to investigate, whether relevant clinical disease characteristics associate with this SNP risk score. Further, for each given clinical outcome, a model was run with all SNPs as potential predictors, and the number of significant associations per SNP counted.

Results

In a total of 2304 genotyped patients, we observed a median number of risk alleles of 167, 168 and 167 for IBD overall, CD and UC/IC, respectively with a narrow inter quartile range [11 (q25 = 162, q75 = 173) for IBD and CD; 12 (q25 = 161, q75 = 173) for UC/IC]. A higher SNP risk score was significantly associated with any complications (defined as a composite of any or more of colorectal cancer, colon dysplasia, intestinal lymphoma, osteopenia/-porosis, anaemia, deep venous thrombosis, pulmonary embolism, nephro- or cholelithiasis, malabsorption syndrome, massive haemorrhage, perforation/peritonitis, pouchitis), stenosis in CD patients; pancolitis, conversion to CD, female sex in UC patients; higher clinical disease activity in both CD & UC.

Regarding individual SNPs, we identified substantial differences in terms of the frequency of associations to disease-related outcomes with up to 11 for rs4899554 in CD and 7 for rs9557195 in UC, respectively.

Conclusion

In our large population of IBD patients there is high per patient frequency of hetero- and homozygous SNP risk alleles. The association of higher SNP risk score with several disease-related outcomes indicates a potential interplay of per patient given SNP risk alleles.
P839 Analysis of mucosa-associated microbiota and serum cytokines levels in Crohn’s disease
Authors: Fukushima S , Shiotani A , Matsumoto H , Inoue R , Naito Y
Published: January 2020

Background

Most studies investigated the intestinal microbiota using stool instead of mucosa-associated microbiota (MAM). We previously analysed MAM using brushing samples during colonoscopy and reported that Actinobacteria was more abundant and Bacteroidetes was less in the brush samples than those in the faecal samples (J Clin Biochem Nutr. 2019;65:132–137). There are few clinical studies investigating correlations between MAM and serum cytokines.

To investigate the diversity and characteristics of MAM in Crohn’s disease (CD) and correlations between MAM and serum levels of inflammatory cytokines.

Methods

CD patients and non-IBD controls who were planning to undergo routine colonoscopy were recruited. 2L polyethylene glycol (PEG) was used as bowel preparation for colonoscopy. Mucosal brushing samples were taken from the ileum and sigmoid colon. 16S rRNA sequencing using the MiSeq system (Illumina, San Diego, CA, USA) was performed. The V3–V4 regions of the gene encoding 16S rDNA (460 bp) were tailed PCR amplified. Processing of sequence data was analysed using QIIME version 1.8.0. Functional changes in the microbiota were evaluated using PICRUSt. Serum cytokine levels were measured using Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel Immunoassay.

Results

The participants were 15 CD patients (average age 43 years, 10 men), and 13 non-IBD controls (average age 58 years, 7 men). The CD group showed a decrease in alpha diversity compared with the non-IBD group, and a significant difference was observed between the two groups in the unweighted PCoA analysis. Bifidobacterium (p = 0.04) and Ruminococcus (p = 0.02) were significantly increased, and Roseburia (p = 0.03) and Oscillospira (p = 0.02) were significantly decreased in the CD group. The component of Bifidobacterium positively correlated with serum IL-15 levels.

Conclusion

MAM in CD group were different from those in non-IBD group, suggesting that certain bacteria may control mucosal immunity.
P846 Comparative study of faecal microbiota in Crohn’s disease patients in remission with and without surgical resection
Authors: Amoedo Cibeira J , Ramió-Pujol S , Serra-Pagès M , Oliver L , Bahí A , Miquel-Cusachs J O , Busquets D , Garcia-Gil J , Aldeguer X
Published: January 2020

Background

Inflammatory bowel disease (IBD) is defined as a group of autoimmune diseases that affects the digestive tract by causing chronic inflammatory processes. Crohn’s disease (CD) is one of the major types of IBD. Although there are several efficient drugs for its treatment, almost 80% of patients will require an intestinal resection throughout their lives. Some bacterial species found in faecal samples can be used as indicators to diagnose and monitor activity in CD patients. However, this methodology has not yet been tested in patients that underwent an intestinal resection. The aim of this study was to investigate the changes in the abundance of these species associated with total or partial intestinal resection.

Methods

In this study, we used 30 faecal samples from patients diagnosed with CD in remission withdrawn from the Biobank of the Hospital Universitari Dr. Josep Trueta of Girona. Fifteen samples corresponded to patients who underwent an intestinal resection. The following markers were quantified by qPCR: Faecalibacterium prausnitzii (Fpra), F. prausnitzii phylogroup I (PHG-I), F. prausnitzii phylogrup II (PHG-II), Escherichia coli (Eco), Akkermansia muciniphila (Akk), Ruminococcus sp. (Rum), Bacteroidetes (Bac) and Methanobrevibacter smithii (Msm).

Results

The abundances of Fpra, PHG-I, PHG-II, Rum, and Msm were significantly lower (p < 0.05) in resected CD patients, whereas Eco was significantly more abundant in those patients. No significant differences were observed in the abundances of Akk and Bac.

Conclusion

In resected CD patients, beneficial butyrate-producing bacteria are underrepresented, whereas pro-inflammatory species are overpopulated. Any quantitative relationship of these indicators with the relapse probability would help to stratify these patients for a better orientation of therapeutic strategies.
P847 A pilot trial on the effect of a fibre-enriched nutritional supplement on the gut microbiota of stricturing Crohn’s disease patients
Authors: Herrera De Guise C M , Varela E , Ibarz A , Burgos R , Cardenas G , Luis Fernando M , Robles V , Borruel N , Guarner Aguilar F , Casellas F
Published: January 2020

Background

Diet is a potential factor that could influence the pathogenesis and activity of Inflammatory Bowel Disease(IBD). Soluble fibre is the best way to generate short-chain fatty acids such as butyrate, which has anti-inflammatory effects. Around 1/3 of Crohn’s disease (CD) patients will present with stricturing disease, most frequently in the terminal ileum. These patients often follow a very low-residue diet. CD patients present significant changes in the structure of their microbiota with a decreased prevalence of butyrate-producing bacteria such as Clostridiales species, particularly Faecalibacterium prausnitzii. Depletion of F. prausnitzii might be further enhanced in patients with a very low-residue diet. The aim of this study was to evaluate the effect of a nutritional supplement enriched with soluble fibre on the abundance of F. prausnitzii in stricturing CD.

Methods

We performed a single arm, pilot trial in CD patients with ileal stricturing disease who followed a very low-residue diet as assessed by a dietician. The fibre-enriched nutritional supplement (reg#26.06141/BA-72556) consisted of a 200ml vanilla-flavoured shake that included 3.4 gr of soluble fibre, omega-3 and oleic fatty acids. Patients received 2 supplements per day for 6 weeks, and were followed for 6 months. We obtained frozen faecal samples at time-points 0, 3, 6, 12 and 24 weeks. Total bacteria and F. prausnitzii counts were assessed by qPCR. Weight, BMI, CD activity index (CDAI), CRP, fatty acids, urine F2-isoprostanes and faecal calprotectin were also determined. Tolerance, palatability and acceptability of the supplement were assessed with validated questionnaires at weeks 3 and 6.

Results

Ten patients were included in the study with a median age of 38 [36–50] years, 60% were male, median BMI 25.2 [24.3–28.4] and 40% were current smokers. Six patients completed the 6 weeks of the supplement. Two patients did not receive the supplement because they underwent ileocecal resection, 1 patient was lost to follow-up and 1 patient dropped-out early because of poor palatability of the supplement. At baseline, all patients had F. prausnitzii levels below 109 CFU/g (median 2.02 × 106). Supplement intake did not significantly increase F. prausnitzii levels (p = 0.73) and had no effect on CDAI, CRP, urine F2-isoprostanes or faecal calprotectin. Most usual complaints associated with the supplement were abdominal bloating and flatulence.

Conclusion

CD patients with structuring disease and who follow a very low-residue diet have a markedly reduced abundance of F. prausnitzii. Intake of a 6.8 g/day fibre-enriched nutritional supplement was unable to significantly increase F. prausnitzii abundance in these patients. Fibre supplement was not associated with adverse events.