bluuebunny/crossref_metadata_2025 huggingface dataset:
P593 Biologicals and small molecule combotherapies: promising experience in refractory IBD patients
Authors: Juillerat P , Martinho-Grueber M , Michetti P
Published: January 2022

Background

It has been hypothesized that combination of two biologics or with a small molecule could ”break the ceiling” of the efficacy (~60%) of currently available biological therapies for IBD patients. The best combinations and their safety are, however, unknown.

Methods

A chart review of Inselspital, Bern University hospital und Crohn and colitis center Beaulieu Lausanne, of IBD patients on combination therapy have been performed. Data on disease phenotype, previous treatment and efficacy and safety of the new combinations have been collected and studied to help moving forward the use of this armentarium.

Results

Among 18 identified IBD patients (39% women, 10 ulcerative colitis, 8 Crohn’s disease) with extended and refractiry luminal disease (indication) who received 21 combination therapies between June 2017 and November 2021. They suffered from steroid-dependency and half of them were refractory to at least two anti-TNF alpha agents. These treatments have been started after a median duration of disease of 6 years (range 1–25) for a mean period of combo treatment of 11 months (range 1–52), 8 were still ongoing. Various combotherapies and clinical response (arrows; red=bad, green=good response) are presented in Figure 1. A partial or complete response was observed in 15/21 therapies (71%) with a mean decrease of CRP of 11 mg/l (range+23 to -59) and calprotectin of 399 mcg/g (range 0 – 1745) among the reponders. Concerning safety, 2 infections (otitis media, skin mycosis), 1 non hodgkin Lymphoma and 4 minor adverse events (tumefaction left parotide, eczema, 2x lymphopenia) have been reported, mostly when small molecules have been involved.

Conclusion

Ustekinumab combined with anti-TNF agents in Crohn’s disease is more effective than vedolizumab and tofactinib in ulcerative colitis. Combining with small molecules increases the risk of lymphopenia, of cancer (1 case of non hodgkin lymphoma) and minor infections in severe refractory and steroid-dependent inflammatory bowel disease patients.
P597 Bone mineral density in patients after total proctocolectomy and pouch surgery due to Ulcerative Colitis have low bone mineral density, and low performance of DXA scans- a cross sectional study
Authors: Pfeffer-Gik T , Godny L , Ollech J , Wasserberg N , Barkan R , White I , Yackobovitch Gavan M , Kraizler M , Yanai H , Dotan I
Published: January 2022

Background

The reported prevalence of low bone mineral density (BMD) in patients with inflammatory bowel diseases (IBD) varies between 20–50%. The multiple contributing factors include inflammation,use of corticosteroids, life style and diet.Patients with ulcerative colitis (UC) undergoing proctocolectomy with ilealpouch-anal anastomosis (IPAA) commonly develop pouchitis-de novo inflammation in previously normal small bowel, which may resemble Crohn’s disease (CD).

We aimed to assess rate of low BMD in patients with a pouch and rate of DXA performance.

Methods

Patients after IPAA due to UC were prospectively followed; Questionnaires regarding demographic, disease course, surgery, diet and blood tests were collected biannually.

BMD was assessed by dual-energy x-ray absorptiometry(DXA).All medical records were reviewed for DXA performance within the last five years, if not found-patients were contacted and submitted the results. Low BMD was defined as T score < -1.

Results

Out of 146 prospectively followed patients, data regarding DXA was available for 114; 70 (61%) women. Median age 46 (IQR 38–67), median age at UC diagnosis 21 years (IQR 15.7–29.5), median pouch age 16 years (IQR 8.5–22.5). DXA scans were performed in 41/114 patients (36%), low BMD was noted in 68.3 %: osteopenia- 16 (39%), osteoporosis: 12 (29.3%). Patients performing DXA scan were older: 54 (IQR 42–64) vs. 45 years (IQR 31–54) (p=0.012), and were diagnosed with UC at younger age: 23 (IQR 17–29) vs. 19 years (IQR 14–26) (p=0.018). Smoking, UC duration prior to IPAA, indication for surgery, pouch age and pouchitis were comparable between patients who performed and did not perform DXA scans. In patients with low BMD- current smoking rates were higher compared to those with normal BMD:4 (14.3%) vs. 0 (p=0.008),respectively. Vitamin D levels in patients with low and normal BMD were comparable:22.8 (IQR 17.5–26) vs. 20 (IQR 16.8–21.8)ng/ml (p=0.158), respectively. Vitamin D supplementation was comparable as well [38% vs. 60% (p=0.16)]. No differences in micronutrients consumption between the groups were noticed.

Conclusion

In a prospective cohort of patients after IPAA due to UC, approximately 36% performed DXA scans and the majority of them had low BMD, with smoking as a potential risk modifier. Due to high rates of low BMD in this population multidisciplinary advice and follow up should be provided to address the low performance of DXA scans and the abnormalities in BMD.
P612 Mirikizumab Pharmacokinetics and Exposure - Efficacy Relationships in Patients with Ulcerative Colitis
Authors: Friedrich S , Chua L , Tuttle J L , Feagan B G , Sandborn W J
Published: January 2022

Background

Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy in a Phase 2 trial in patients with moderately-to-severely active ulcerative colitis (UC)1 (NCT02589665). Analyses of the pharmacokinetics (PK) of miri and the relationships between exposure and efficacy at Week 12 are reported.

Methods

Patients were randomised to receive IV placebo, miri 50 mg or 200 mg with possibility of exposure-based dose increases, or miri 600 mg every 4 weeks, with efficacy assessment at Week 12. Serum concentrations of miri were analyzed using population PK methods. Population models were also used to evaluate the relationships between various clinical efficacy measures at Week 12 and miri exposure. The effects of patient factors on both PK and exposure-efficacy relationships were evaluated. Model-based and graphical methods were also used to understand the potential for confounded relationships between miri exposure and efficacy.

Results

A systemic clearance of 0.023 L/hr was estimated for miri, similar to estimates in healthy subjects and patients with psoriasis. Miri exposure increased in a linear manner. Patients with lower serum albumin concentration or lower body weight tended to have significantly higher clearance or lower volume of distribution, respectively (p<0.01); however, the magnitude of the impact was small and contributed less than 15% to random variability. The model-based exposure-response analyses generally showed that patient factors had a stronger impact on efficacy at Week 12 than miri exposure. Prior biologic experience and baseline rectal bleeding (RB) score had significant impacts (p<0.01) on the estimated placebo effect and maximal miri treatment effect (Emax), respectively. In the clinical response model, the estimated placebo response rate was 20 percentage points higher in biologic naïve vs experienced patients. The estimated response rate at a miri dose of 600mg was 28% higher in patients with a baseline RB≥2. Inclusion of these factors in the exposure-efficacy models caused the estimated EC50 to drop substantially, suggesting that the post-hoc exposure-efficacy relationships are likely confounded based on these patient factors. Graphical evaluations also suggested the presence of confounding factors.

Conclusion

Miri PK in UC patients was consistent with PK observed in healthy subjects and psoriasis patients. Evaluation of the relationships between miri exposure and efficacy in UC patients accounted for the potential impact of patient factors. Confounding patient factors may distort the true cause-effect relationship between exposure and efficacy and were carefully considered in support of optimal selection of doses for miri Phase 3 studies.

Reference

1. Gastroenterology. 2020;158(3):537–549.
P619 Patterns of Anti-TNF Prescribing & Therapy Outcome in a Large Multicentre Cohort of Inflammatory Bowel Disease Patients
Authors: Doherty J , Stack R , O Morain N , Coe C , Corcoran R , Ryan B , Doherty G , Mc Namara D , Kevans D
Published: January 2022

Background

Anti-TNF agents are effective therapies for Inflammatory Bowel Disease (IBD), however, a significant proportion of patients lose response over time. Real world data on prescribing practices and outcome of anti-TNF therapy are of utility to practicing clinicians

Methods

To evaluate Anti-TNF prescribing practice and durability of Anti-TNF response in a large multicentre IBD cohort. IBD patients commencing an anti-TNF agent, as first biologic therapy, at participating academic centres were identified from institutional databases. Baseline demographic data, concomitant medication and biologic therapy history were collected. Adalimumab(ADA) and Golimumab(GOL) were consider subcutaneous(SC) anti-TNF agents. Date of commencement and discontinuation of first and second line anti-TNF therapy was documented. Kaplan-Meier survival curves were constructed for time based analyses. P values less than 0.05 were considered significant in all analyses.

Results

N=991 patients with IBD were included in the study. 29%, 69% and 2% had UC, CD and IBD-U respectively; median [IQR] age 27 [19–37] years; 50% female. 31%, 63% and 4% received infliximab(IFX), ADA and GOL respectively as first-line anti-TNF therapy. 35% of patients received an immunomodulator in combination with first-line anti-TNF agent. Median [95% CI] survival free of therapy discontinuation for first and second-line anti-TNF agents was 4.6 [3.7 – 5.3] years and 3.0 [2.1 – 3.9] years respectively. Survival free of anti-TNF discontinuation was significantly shorter for IFX monotherapy group compared with IFX combination therapy, SC anti-TNF monotherapy and SC anti-TNF combination therapy groups, p=0.005.

Conclusion

While anti-TNF therapies are effective a significant proportion of patients discontinue therapy over time. Second line anti-TNF therapy results in a less durable response with a shorter time to drug discontinuation compared with first line anti-TNF therapy. The use of a combination immunomodulator is particularly important with infliximab therapy, however, does not influence durability of response for subcutaneous anti-TNF agents.
P629 Evolution of disease phenotype, time to biological therapy and medium-, long-term surgery rates in Crohn’s disease patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem county cohort
Authors: Gonczi L , Lakatos L , Golovics P , Pandur T , David G , Erdelyi Z , Szita I , Lakatos P L
Published: January 2022

Background

The number of prospective population-based studies evaluating the natural disease course and surgical outcomes of Crohn’s disease(CD) are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to evaluate disease course by examining progression in disease phenotype, time to biological therapy and surgery rates in a prospective population-based database from Veszprem Province, including incident CD patients diagnosed between January1,2007 and December31,2018.

Methods

Data of 421 incident CD patients were analyzed(male/female:237/184; median age at diagnosis:29 years(y)[IQR: 21–42]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The mean length of follow-up was 8.53y(SD: 3.3). Probability of medium-, long-term change in disease course and surgical outcomes were analyzed.

Results

Disease location was ileal(L1), colonic(L2) in and ileo-colonic(L3) in 29.7%/24.5%/45.8% of patients at diagnosis. At the end of follow-up(8.53y), disease location was 27.1%/22.8%/50.1%(L1/L2/L3). The proportion of patients with upper gastrointestinal manifestation remained stable(7.6% and 8.1%), while perianal disease increased from 13.5% to 19% by the end of follow-up. Disease behavior at diagnosis was luminal(B1) in 62.5% of the patients. The probability of disease behavior progression from luminal into stenosing or penetrating phenotype was 11.9%(SE:1.7) at 3 years, 13.2%(SE:1.7) at 5 years and 17.6%(SE:1.7) at 10 years.Figure 1. The Probability of receiving biological therapy after diagnosis was 20.9%(SE:2.0) at 5 years and 28.8%(SE:2.0) at 10 years in this cohort. Overall resective surgery rate was 29.5% in the total population, while perianal surgery rate was 31.3% in patients with perianal disease at the end of follow-up. The probability of resective surgery was 20.7%(SE:2.0) at 1 year, 26.1%(SE:2.2) at 5 years and 30.7%(SE:2.4) at 10 years.Figure 2. For the probability of first perianal surgery among patients with perianal disease see Figure 3.

Conclusion

The probability of progression in disease behavior was lower compared to data from previous decades and similar to results from recent pan-European population-based data.(Burisch 2018, JCC). One-year surgery rates after diagnosis were considerably higher compared to previous data from our cohort or compared to Western and Northern European centers.(Lakatos 2011, IBD). Medium-term(5y) surgery rates were similar(~20%) compared to recent Hungarian and European data, while long-term(10y) rates decreased compared to data from previous decades.(Lakatos 2011,IBD; Lakatos 2012,AJG).
P641 Implementation and short-term adverse events of anti-SARS-CoV-2 vaccines in Inflammatory Bowel Disease patients: an international web-based survey
Authors: Revés J , Abreu B , Chaparro M , Gisbert J P , Mariangela A , Fiorino G , Barberio B , Zingone F , Pisani A , Cassar D , Michalopoulos G , Mantzaris G , Mountaki K , Koutroubakis I , Karmiris K , Katsanos K , Ďuricova D , Burisch J , Madsen G R , Maaser C , Naila A , Orfanoudaki E , Milivojevic V , Buisson A , Avedano L , Leone S , Torres J , Ellul P
Published: January 2022

Background

Pivotal anti-SARS-CoV-2 vaccines clinical trials did not include patients with immune-mediated conditions such as inflammatory bowel disease (IBD). We aimed to describe the implementation of anti-SARS-CoV-2 vaccines among IBD patients, patients’ concerns before vaccination and side-effect profile of the anti-SARS-CoV-2 vaccines using real-world data.

Methods

An anonymous web-based self-completed survey was distributed in 36 European countries between June and July 2021. The results of patients’ characteristics, concerns, vaccination status and side-effect profile were analysed using descriptive statistics and logistic regression.

Results

Among the 3272 IBD patients completing the survey (0.1% of the IBD European population), 79.6% had received at least one dose of the anti-SARS-CoV-2 vaccine, and 71.7% had completed the vaccination process. Most of the patients (70.6%) were vaccinated with the Pfizer-BioNTech (BNT162b2) vaccine. Patients over 60 years old had a significantly higher rate of vaccination (OR 2.98, 95% CI 2.20–4.03, p<0.001). Patients’ main concerns before vaccination were the possibility of having worse vaccine-related adverse events due to their IBD (24.6%), having an IBD flare after vaccination (21.1%) and reduced vaccine efficacy due to IBD or associated immunosuppression (17.6%). After the first dose of the vaccine, 72.4% had local symptoms at the injection site and 51.4% had systemic symptoms (5 patients had non-specified thrombosis). Adverse events were less frequent after the second dose of the vaccine and in older patients. When comparing with previous studies from the general population, the IBD patients answering the survey did not seem to have increased side effects (Table 1). Only a minority of the patients were hospitalized (0.3%), needed a consultation (3.6%) or had to change IBD therapy (13.4%) after anti-SARS-CoV-2 vaccination.

Conclusion

Although IBD patients raised concerns about the safety and efficacy of anti-SARS-CoV-2 vaccines, the implementation of vaccination in those responding to our survey was high and the adverse events were comparable to the general population, with minimal impact on their IBD.
P646 Will the screening of SARS-COV-2 infection in IBD infusion centers be useful?
Authors: Abreu N , Oliveira A , Morna H , Jasmins L
Published: January 2022

Background

The global emergence of SARS-COV-2 virus and the COVID-19 pandemic increased the concerns about the vulnerability of inflammatory bowel disease (IBD) patients. Infusion centers are a crucial part in the management of IBD patients and safety for SARS-COV-2 must be assured. Current recommendations of International Organization for the Study of Inflammatory Bowel Disease suggest that only patients exhibiting symptoms suggestive of COVID-19 should be tested for SARS-COV-2 before the biologic infusion therapy. We evaluated patients admitted at our infusion center, in which all had to be screened before treatment.

Methods

We conducted an observational study, including all adult patients with IBD under biologic therapy infusion between April of 2020 and September of 2021. According to the local institutional protocol all patients were tested for SARS-COV-2 by a polymerase chain reaction (PCR) test in the previous 48–72 hours. Epidemiological, clinical and treatment data were collected.

Results

A total of 105 patients were evaluated, with a mean age of 38,6±12,8 years and a predominance of male gender (61,9%). Crohn’s disease was more prevalent, affecting 81,9% of the patients. The most common biologic infusion therapy was infliximab (93,3%), followed by vedolizumab (4,8%).

A SARS-COV-2 infection were identified in five patients (4,8%), with age between 41 and 66 years, four asymptomatic and without a known risk contact. Four patients developed the infection before vaccination and one patient after the first dose. None of the patients required medical care or hospitalization.

All cases were registered in February of 2021, which temporarily represented one of the most critical phases of the pandemic in our country and region, with one of the highest incidence of cases of SARS-COV-2 infection.

In our cohort, most patients (85,7%) completed the vaccination schedule, with a minority (n=10) without any dose of vaccine.

Conclusion

During this COVID-19 pandemic, health systems have to address unprecedented challenges. Our study support the current recommendation, since the universal screening of SARS-COV-2 infection in IBD patients, before the biological infusion therapy, detected just a few cases of infection. However this recommendation could be adapted locally, maybe when there is raising incidence of SARS-COV-2 in the general population. Our cohort also showed high compliance for the vaccination as general recommendation and even after the infection.
P658 Evolution of disease phenotype, time to biological therapy and medium-, long-term colectomy rates in Ulcerative Colitis patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem county cohort
Authors: Gonczi L , Lakatos L , Golovics P , Pandur T , David G , Erdelyi Z , Szita I , Lakatos P L
Published: January 2022

Background

The number of prospective population-based studies evaluating the natural disease course and surgical outcomes of ulcerative colitis (UC) are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to evaluate disease course by examining progression in disease phenotype, time to biological therapy and colectomy rates in a prospective population-based database from Veszprem Province, including incident UC patients diagnosed between January 1, 2007 and December 31, 2018.

Methods

Data of 467 incident UC patients were analyzed (male/female: 236/1231; median age at diagnosis: 36 years(y) [IQR: 25–54]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The mean length of follow-up was 8.34y (SD: 3.5). Disease phenotype was evaluated based on the Montreal classification. Probability of medium-, long-term change in disease course and surgical outcomes were analyzed using Kaplan–Meier survival analysis.

Results

Disease extension was proctitis (E1), left sided colitis (E2), and extensive colitis (E3) in 22.3%/ 43.9%/ 33.8% of patients at diagnosis. The probability of disease progression into more extensive phenotype was 6.9% (SE:1.2) at 3 years, 8.3% (SE:1.3) at 5 years and 11.3% (SE:1.6) at 10 years. Figure 1. The Probability of receiving biological therapy after diagnosis was 9.9% (SE:1.4) at 3 years, 13.9% (SE:1.6) at 5 years and 17.8% (SE:2.0) at 10 years in this cohort. Overall colectomy rate was 4.1% in the total population at the end of follow-up. The probability of colectomy was 1.5% (SE:0.6) at 1 year, 3.6% (SE:0.9) at 5 years and 4.4% (SE:1.0) at 10 years in Kaplan-Meier analysis. Figure 2.

Conclusion

The probability of progression in disease extent was low overall, similar to results from recent pan-European population-based data. (Burisch 2019, JCC). Medium- and long-term colectomy rates were lower compared to Western European centers, but somewhat higher compared to our previous data from the Veszprem cohort (2002–2006). (Lakatos 2011, IBD).
P665 Towards FAIR longitudinal IBD registries: preliminary results of an iterative design process of a reusable and interoperable IBD database model
Authors: Adriaans G M C , Hendrix E M B , Creemers R , Janssen L , Demers K , Rezazadeh Ardabili A , Jonkers D M A E , Pierik M J
Published: January 2022

Background

The Real World Data [RWD] of the Dutch longitudinal IBD registries (population based IBD South Limburg cohort, Parelsnoer IBD, Initiative on Crohn and Colitis drug-registry) have proven to answer knowledge gaps regarding epidemiology, patient stratification, positioning and effectiveness and safety of new drugs. Life-long data-capture in registries for large cohorts is extremely labor intensive and expensive.

Therefore, based on the database models of existing registries, we aim to develop a reusable and interoperable Real World IBD database model that will contribute re-use of every-day care data form hospital information systems and remote monitoring platforms. This project contributes to generation of high quality, multi-dimensional data for (inter)national IBD registries such as the United Registries for Clinical Assessment and Research [UR-CARE] registry and aforementioned registries.

Methods

The design process was iterative and involved the potential end-users of the registries.

For the first iteration the database models of established Dutch IBD cohorts were taken as input, in combination with repeated discussions on the content with three principal IBD investigators.

The second iteration was multifaceted including; 1) Five discussion sessions with 7 IBD researchers (MD medicine of which the majority practiced IBD care and were experienced with the hospital information system) discussing the content, and 2) four discussion sessions with researchers experienced in re-using hospital care data for research that evaluated the model on practical use and difficulties in data interpretation using the output of the first iteration. No data was analyzed, only codebooks describing variables and their values.

Results

The first iteration of the design phase resulted in a database model called IBD common data model [IBDCDM] v1 consisting out of 395 variables, and based on existing codebooks of Dutch IBD registries (figure 1).

The database model, called IBD common data model [IBDCDM] v1 consists out of 27 independent modules on different themes important for the IBD disease course allowing for repeated data recordings (figure 2).

The second iteration of the design phase resulted in pruning the modules’ content, removal of one module, merging and adding of modules.

Conclusion

An iterative design process involving end-users will result in higher data quality by optimizing practical usability and interpretability of the database model. Next step is to encode the model using medical standardized vocabularies (e.g. SNOMED, LOINC), for interoperability.

The database model contributes towards producing reusable IBD datasets that use study hospital care data as a primary source to study the IBD disease course over several decades.
P672 Biologic therapy for Inflammatory Bowel Disease in Poland in 2020: nationwide data
Authors: Kucha P , Zagórowicz E , Walkiewicz D , Perwieniec J , Maluchnik M , Wieszczy P , Reguła J
Published: January 2022

Background

The number of patients in Poland diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) has been increasing in the last decade, which implies an increase in the number of severe cases, where biologic treatment is required. The aim of this study was to analyse the usage of biologic treatment among patients with both types of inflammatory bowel diseases (IBD) in Poland that was reimbursed by the National Health Fund (NFZ) in 2020.

Methods

The analysis was conducted using administrative data collected since the year 2009 by the National Health Fund (NFZ), the only public payer in Poland. We defined an IBD patient receiving biologic treatment as a patient: (1) who had at least two inpatient/outpatient records in the NFZ registry in the years 2009 – 2020 with ICD10 code K50/K51 assigned; (2) who had filled at least two prescriptions for IBD medications two months apart or who had undergone intestinal surgery prior to the record; (3) and who received biological treatment reimbursed by the NFZ in 2020. We assessed the total percentage of patients with each diagnosis who received biologic treatment as well as the percentage by sex, by age group and by the place of residence (voivodeship).

Results

In 2020, the percentage of patients treated with biologic agents in the population of CD patients was 7.9% (1 863 / 23 574). The percentage of patients treated with biologic agents in the population of UC patients was 1.6% (1 174/73 235). The rate of patients treated with biologics for both CD and UC was significantly lower in women than in men (p<0,001 for both). Among all age groups, the highest percentage of patients receiving biologic treatment for both CD and UC (21,7% and 6,5%, respectively) was observed in those aged 10–19 years and the lowest percentage in patients aged over 70 years (0,8% for CD, 0,2% for UC). The highest proportion of patients treated with biologic drugs among CD patients was found in the Mazovian Voivodeship (13.8%) and the lowest - in the Lubusz Voivodeship (1.2%). In UC, the highest biologic treatment rate was observed in the Świętokrzyskie Voivodeship (3.1%), and the lowest in the Lubusz Voivodeship and the Warmian-Masurian Voivodeship (both 0.2%).

Conclusion

The use of biologic agents in the treatment of both Crohn’s disease and ulcerative colitis in Poland has been presented. Female patients receive biologic treatment for IBD significantly less frequently than male. The highest proportion of patients receiving biologic treatment for both CD and UC was found in the paediatric population. There are voivodeships in Poland where the access to biological treatment is unacceptably low.
P676 Burden of depression and anxiety among inflammatory bowel disease patients in a national cohort in Israel – Data from the EPI-IIRN
Authors: Mekori - Domachevsky E , Ziv - Baran T , Loewenberg Weisband Y , Greenfeld S , Kariv R , Erez M , Friss F , Focht G , Turner D , Ben - Horin S , Kopylov U
Published: January 2022

Background

Depression and anxiety in inflammatory bowel disease (IBD) patients have been receiving much deserved attention in recent years, as consecutive studies demonstrated that these emotional disorders are both common and detrimental for IBD patients. The aim of the current study was to examine the prevalence of depression and anxiety in a national cohort of IBD patients in Israel.

Methods

The epi-IIRN is a validated cohort of all IBD patients in Israel, ensured in four health maintenance organizations (HMOs). In this historical cohort study we included data from three HMOs, encompassing ~85% of Israeli population, between December 1997 [TD1] [UM2] and December 2019. Data included demographic data (age, sex and socioeconomic status), medical data (diagnosis type, time of diagnosis, medical regiments) and mental health status (a diagnosis of depression / anxiety defined by the relevant ICD9 codes or use of antidepressants / anxiolytics for at least two year quarters). For each IBD patient identified, three non-IBD subjects were allocated. Patients younger than 18 years or with a diagnosis of depression / anxiety preceding the diagnosis of IBD were excluded. Using cox regression and Kaplan Meier survival curve, we evaluated the prevalence of comorbid depression / anxiety at 5, 10 and 15 years following the diagnosis of an IBD.

Results

A total of 31340 IBD patients (48.1% females, mean age at diagnosis 38.6±15.9) and 91535 controls (48.7% females, mean age 39.9±16.1) were identified. The risk of depression / anxiety comorbidity was higher in IBD patients in comparison to controls at all evaluated timepoints: At 5 years following a diagnosis of IBD the hazard risk ratio (HR) was 1.48 (95% CI 1.43 – 1.53, p < 0.001, 15.5% vs 10.6%,); at 10 years HR was 1.38 (95% CI 1.34 – 1.42, p < 0.001, 22.9% vs. 17.0%) and at 15 years 1.37 (95% CI 1.33 – 1.40, p < 0.001, 27.5% vs 21.0%). For all analyses, female gender was a risk factor for development of depression/anxiety (HR~1.5, p < 0.001). IBD type (Crohn’s disease / ulcerative colitis) was not significantly associated with the risk of comorbid depression / anxiety.

Conclusion

Our national study highlights the substantial burden of depression and anxiety in IBD patients that is persistent for up to 15 years after diagnosis. Our findings emphasize the need to monitor for potential symptoms of depression and anxiety among our patients, as well as the need for prompt intervention and follow-up by a mental health care provider when such symptoms are identified.
P680 Epidemiology of Inflammatory Bowel Disease in Poland 2009–2020: nationwide data
Authors: Zagórowicz E S , Walkiewicz D , Kucha P , Perwieniec J , Maluchnik M , Wieszczy P , Reguła J
Published: January 2022

Background

The epidemiology of inflammatory bowel disease (IBD) in Poland has only been recognised to a limited extent. We aimed to estimate the prevalence and incidence of the disease by analysing data from the National Health Fund, the sole public health insurer.

Methods

Administrative health claims collected over the 2009–2020 period were used to identify patients with Crohn’s disease (CD) or ulcerative colitis (UC). A definition of a case comprised ≥2 records assigned K50 or K51 codes, plus ≥2 prescriptions for IBD drugs reimbursed, or else intestinal surgery preceding the record. The crude and European age-standardised rates (EASR) and 95% confidence intervals (CI) were calculated for the prevalence and incidence. Time trends were also analysed.

Results

As of 2020 there were 23,574 patients with CD and 73,235 with UC. The CD and UC prevalence was respectively 61.6 [EASR 60.3 (95% CI 59.5–61.0)] and 191.4 [EASR 187.85 (95% CI 186.5–189.2)] per 100,000. The prevalence of CD was higher in men [64.1; EASR 61.3 (95% CI 60.2–62.5)] than in women [59.3; EASR 58.4 (95% CI 57.3-59,5)]. Similarly, the prevalence of UC was higher in men [201.4; EASR 202.7 (95% CI 200.5–204.8)] than in women [182.0; EASR 175.5 (95% CI 173.7–177. 4)]. The incidence of CD was 4.7 per 100 000 [EASR 4.6 (95% CI 4.4–4.8)], while of UC 12.5 [EASR 12.3 (95%CI 12.0–12.7)]. Through the period 2012–2018, the prevalence of both conditions rose, even as downward trends were noted for disease incidence.

Conclusion

The prevalence and incidence of IBD in Poland are presented, with time trends showing substantial increase in the disease burden over the years 2009–2020.
P681 Impact of Crohn’s disease on survival in Korean patients with small bowel adenocarcinoma
Authors: Kim K , Choi K , Hwang S W , Im J P , Ye B D , Kim J S , Yang S K , Koh S J , Park S H
Published: January 2022

Background

In comparison with the general population, patients with Crohn’s disease (CD) are at higher risk of developing small bowel adenocarcinoma (SBA). However, with low prevalence of SBA, data regarding the impact of CD on survival are lacking. We investigated the impact of CD on survival in patients with SBA.

Methods

From January 1998 through July 2021, patients with histologically confirmed SBA were retrospectively collected and classified into binary, namely, sporadic SBA and CD-associated SBA groups. Patients with duodenal SBA were excluded. The overall survival (OS) and factors associated with survival were analysed.

Results

Of 127 patients with SBA, 115 patients were sporadic SBA and 12 were CD-associated SBA (Table 1). Compared to patients with sporadic SBA, poorly differentiated tumour was more common among patients with CD-associated SBA (41.7 vs. 14.8%, p=0.030). Other baseline demographic characteristics including age at the diagnosis of SBA, sex, Charlson morbidity score more than 2 points, smoking history, family history of cancer, location of SBA, initial stage based on American Joint Committee on Cancer (AJCC) staging system, and treatment showed no significant difference. In survival analyses, the 1-year (yr), 2-yr, and 5-yr OS were lower in patients with CD-associated SBA, without statistical significance (1-yr OS; 81.8 vs. 90.5%, 2-yr OS; 61.4 vs. 81.7, 5-yr OS; 61.4 vs. 69.1%, p=0.590) (Fig 1). Factors associated with decreased survival were disease stage (AJCC stage IV) (hazard ratio [HR] 5.485; 95% confidence interval [CI], 2.442–12.279, p<0.001) and palliative treatment (HR 2.447; 95% CI, 1.064–5.624, p=0.035), whereas curative operation plus adjuvant chemotherapy improved survival (HR 0.335; 95% CI, 0.132–0.849, p=0.021) (Table 2). Crohn’s disease was not significantly associated with survival (HR 1.333; 95% CI, 0.472–3.769, p=0.587).

Conclusion

The OS of patients with CD-associated SBA was not significantly lower than that of patients with sporadic SBA. The independent risk factors for survival were the stage of SBA and type of treatment, not Crohn’s disease.
P693 Willingness and hesitancy to the telemedicine in patients with inflammatory bowel disease during COVID-19 outbreak. Preliminary results of a survey in an Italian IBD Center
Authors: Bossa F , Guerra M , Carparelli S , Antonella M , Terracciano F , Costantino A , Caprioli F , Valvano M R , Martino G , Nardella M , Perri F
Published: January 2022

Background

Telemedicine is becoming a necessary tool for chronic disease management. Thanks to the wide diffusion of devices connecting to the World Wide Web, a large part of the population are now able to access to telemedicine services.Telemedicine is becoming a necessary tool for chronic disease management. Thanks to the wide diffusion of devices connecting to the World Wide Web, a large part of the population are now able to access to telemedicine services.

The aim of this survey was to explore the willingness and hesitancy of patients with inflammatory bowel disease (IBD) to the use of telemedicine during COVD-19 outbreak.

Methods

A paper-and-pencil questionnaire was proposed to all consecutive patients observed at our tertiary IBD center in San Giovanni Rotondo (Italy) from February to May 2021. The survey investigated 20 items that can be grouped into 5 areas: socio-demographic data, clinical data, informatics competence, devices and network utilized for the internet connection, attitude to the telemedicine, and the impact of COVID-19 pandemic.

Results

A total of 156 patients completed the questionnaire (100 males). One hundred forthy-three patients (91.7%) were under 65 years and only 15 (9.6%) were graduates. Forthy-seven patients (30%) were single, 101 married (65%). Eighteen patients (11.5%) felt they had no IT skills. Eight patients (5.1%) had a previous experience of telemedicine. One hundred twenty-three patients (78.8%) consider the support of telemedicine useful for the management of their pathology and 134 (85.9%) would like the Center where they are followed up to have the possibility of offering a telemedicine service. One hundred three patients (66.0%) would like to have a teleconsultation with figures other than the Gastroenterologist. Ninety-seven patients (62.2%) agree that the ongoing coronavirus pandemic has a major impact on the need to implement telemedicine. Regarding the confidence with telemedicine, 106 patients (67.9%) were partially or totally agreeing telemedicine can properly resolve health problems, and 98 (62.8%) agree that technologies guarantee the privacy of the health data. One hundred twenty-five patients (80%) agree that telemedicine should be developed independently of the pandemic, however only 48 patients (31%) believe that telemedicine guarantee the same level of assistance of visit in presence.

Conclusion

Italian IBD patients showed a positive attitude towards telemedicine and consider that useful for the management of their disease. The majority of patients would like the center where they are followed up offering a telemedicine service, regardless of the ongoing pandemic. However only one third of patients believe that telemedicine can offer the same level of assistance of in-presence visit.
P697 Examining the regulatory role of epigenetic and transcriptomic alterations in anti-TNFα treatment response and disease progression in patients with Ulcerative Colitis
Authors: Lawal O , Stack R , Ciara E , Tosetto M , McDonnell C , Rodriguez-Sosa A , Yochum G , Koltun W , Boland K , Sheahan K , Doherty G , Das S
Published: January 2022

Background

Ulcerative colitis (UC) is a chronic inflammatory condition characterized by significant morbidity and escalating economic costs. Effective patient management is severely hampered by a lack of unambiguous molecular biomarkers that can predict response to anti-TNFα treatment such and/or disease progression. While, both genetic and epigenetic factors have been reported to impact UC pathogenesis, their role in regulating disease progression and treatment response remains unclear.

Methods

Here, we applied methyl-capture sequencing and RNAsequencing to mucosal biopsies derived from clinical cohorts of patients with mild-to-moderate and severe UC with the aim of identifying various regulatory factors that orchestrate treatment response and disease severity in these patients.

Results

First, differential gene expression analysis between responders and non-responders to infliximab and vedolizumab (anti-TNFα) enabled identification of disease-associated genes that were either up- or down-regulated in responders to both these anti-TNFα agents. Next, upstream analysis of these differentially expressed genes revealed that both up- and downregulated genes in responders are intricately regulated by “master regulators” (MRs) including chemokine ligands and receptors such as FGFR2 and IL8 respectively. Moreover, we show that these MRs play a pivotal role in regulating gene expression through a complex signalling network mediated by transcription factors (TFs) such as FYN and ICAM1. These results for the first time provide evidence of impact of MRs and TFs on genes involved in differential response to anti-TNFα agents in patients with UC. In parallel, targeted DNA methylation profiling of mucosal biopsies derived from mild-to-moderate (n=85) and severe UC (n=33) patients enabled identification of a wide-spread DNA methylation alterations at regulatory regions such as promoters and enhancers. Moreover, we identified distinct significant methylation differences between UC patients who progress in their disease course leading to treatment with anti-TNFα/immunodulators agents vs. patients who are on 5’Asa maintenance treatment. Indeed, similar differences was also observed between responders and non-responders of anti-TNFαagents.

Conclusion

Taken together, our preliminary results for the first time highlight the regulatory role of master regulator-mediated signalling networks involving transcription factors that regulate gene expression underpinning response to anti-TNFa in UC patients. In parallel, these results identify specific DNA methylation alterations that impact treatment response and disease severity and therefore could ultimately enact as predictive biomarkers in UC.
P703 Gut bacteria composition and familiality echo Inflammatory Bowel Disease type and pathological spectrum
Authors: Martinez-Gili L , Gordon H , Blad W , McDonald J A K , Holmes E , Marchesi J R , Harbord M
Published: January 2022

Background

Inflammatory bowel disease (IBD) aetiology encompasses genetic and environmental factors. Twin studies provide valuable insights to the familial degree (shared genetics and environment) of observed phenotypes. We characterised the gut bacterial composition of twins with IBD to find taxa associated with disease and estimate their familiality.

Methods

Faecal samples were collected from 88 monozygotic (MZ) and dizygotic (DZ) twin pairs concordant or discordant for Crohn’s disease (CD; 26 MZ; 19 DZ) or ulcerative colitis (UC; 16 MZ; 27 DZ). The 16S rRNA gene was sequenced and amplicon sequence variants (ASV) generated. ANCOM software was used to assess differences in IBD vs. non-IBD, stratifying by disease type (CD/UC) and adjusting for age, gender and smoking. Twin pair and zygosity were added as random effects to estimate familiality, defined as percentage of variation due to common environment and genetics. IBD-affected twins were used for differences in disease location or treatment. Participants reporting antibiotic/probiotic treatment within the last 3 months or with a stoma/pouch were not included. In UC, surgery-naive patients were compared to an excluded subset who underwent ileostomy or pouch surgery without any recent antibiotic courses.

Results

Disease concordance in MZ twins was higher in CD (54%) than UC (19%). Alpha diversity was lower in CD, but not UC, and in ileostomy and pouch vs. surgery-naive UC. Principal component analysis showed that CD-affected twins clustered apart from non-IBD ones (Figure 1A). Familiality was lower in CD, with 5% of ASVs having familiality > 50%, compared to 17% in UC (Figure 1B). Two Lachnospirales order ASVs were less abundant in UC, while 15 ASVs from Clostridia, Bacteroidia, Bacilli and Coriobacteriia classes differentiated CD from non-IBD. Firmicutes were higher in CD (β= 0.95; 95%CI [0.34,1.56]), while no phyla changed in UC. Veillonella, Barnesiella, Faecalimonas and Holdemania genera had opposite trends in ileocolonic or colonic CD vs. ileal, and two Clostridia ASVs were lower in extensive and left-sided UC. Gemmiger and Butyricicoccus_A genera were reduced in UC patients taking aminosalicylates compared to untreated. No treatment differences were found in CD. Patescibacteria was higher in ileostomy and Verrucomicrobiota in pouch, while Bacteroidota and Firmicutes_A were lower in both surgeries.

Conclusion

Despite higher disease concordance, gut bacteria familiality in CD was lower than UC, indicating that bacterial composition is an information-rich matrix which captures the heterogeneity of IBD clinical manifestations. Accordingly, we found taxonomic changes specific to IBD presence, but also location, medication, or surgery.
P708 Ileal involvement defined by Montreal classification in Crohn’s disease is associated with a distinct microbial composition in ileal and colonic mucosa
Authors: Hernandez-Rocha C , Nayeri S , Turpin W , Borowski K , Stempak J , Silverberg M S
Published: January 2022

Background

The Montreal classification of inflammatory bowel disease (IBD) recognizes distinct subgroups based on location of disease, age at onset and behaviour for Crohn’s disease (CD) and extent in ulcerative colitis (UC). CD with ileal involvement is in part genetically determined and tends to progress to surgery and to be more refractory to medical therapy compared to colonic disease location. We investigated the association of different aspects of the Montreal classification with the ileal and colonic mucosa-associated microbiota.

Methods

Healthy control (HC) and IBD patients underwent colonoscopy with biopsy samples taken from terminal ileum, ascending and sigmoid colon. Mucosal 16s rRNA gene profiling was analysed and an amplicon sequence variant table was generated and normalized. Patients with prior intestinal resection, IBD-unclassified and recent antibiotic exposure were excluded. Endoscopic activity was defined as a segmental Mayo endoscopic subscore > 0 in UC and a simple endoscopic score > 2 in CD. Blood samples were drawn for genotyping and a weighted genetic risk score (GRS) was built based on 169 IBD risk variants. Pooled ileal and colonic samples were analysed for taxonomic differential abundance (DA) among the variables of the Montreal classification using a linear mixed-effects model (MaAsLin2) with age, sex, biopsy site, endoscopic activity and GRS as covariates. P-values were corrected for false discovery rate (FDR) and < 5% was considered significant.

Results

A total of 546 biopsy samples from 201 IBD patients and 48 HC were analysed. The characteristics of the cohort and Montreal classification are depicted in the Table. At colonoscopy 168 samples (31.4%) showed endoscopic activity. The multivariate analysis revealed that the genera Agathobacter and Faecalibacterium, as well as the family Ruminococacceae and the order Oscillospirales were significantly reduced in CD with ileal involvement (L1+L3) when compared to either isolated colonic CD (L2), UC (any extent) and HC independent of age, sex, endoscopic activity, biopsy site, and GRS (Figure). Samples from UC and isolated colonic CD patients did not show differences in their microbial profile irrespective of biopsy site. No differences in DA were observed in subgroups based on age at onset and disease behaviour in CD or extent in UC. GRS was not associated with microbial composition.

Conclusion

These data suggest that CD with ileal involvement (Montreal L1+L3) is a major determinant of the tissue-associated microbial composition in both ileal and colonic mucosa irrespective of variables such as endoscopic activity and GRS. The reduction of several beneficial microbes in CD with ileal involvement might partially explain the more progressive phenotype in such patients.