bluuebunny/crossref_metadata_2025 huggingface dataset:
P211 Vaccination against Sars-Cov-2 in IBD patients: experience from a single tertiary referral centre
Authors: Bezzio C , Guarino A D , Arena I , Della Corte C , Devani M , Manes G , Schettino M , Sablich E , Vernero M , Saibeni S
Published: January 2022

Background

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 have afflicted millions of people in a global pandemic. Recently developed vaccines against SARS-CoV-2 represent one of the most important tool in limiting widespread of infection. However, it is known that vaccination rates in IBD patients are suboptimal. The aim of this study was to compare clinical and socio-demographic features of IBD patients undergoing or not vaccination against SARS-CoV-2, and assess the reasons of who expressed their consent.

Methods

A questionnaire was administered to all consecutive IBD contacted by a tertiary referral center for vaccine against SARS-CoV-2 from April 10th 2021 to May 16th 2021. Comparisons of prevalence were assessed by Fisher’s exact test (significance level p<0.05)

Results

475 IBD patients were contacted by phone call: 28 of them were not reachable, 98 were already vaccinated. Of the remaining 349 IBD patients, 324 (92.8%) accepted to be vaccinated while 25 (7.2%) refused. The questionnaire was compiled by 248/324 (76.5) of accepting and by 19/25 (76.0%) of refusing patients. Their demographic, social and clinical features are shown in Table 1. Among the different variables, only a previous unwillingness to be vaccinated against influenza was associated with the refuse of vaccine anti-SARS-CoV-2. Age, sex, diagnosis, marital status, educational level, employment, previous COVID-19 and biologics and/or immunosuppressants were not associated with the decision to be vaccinated or not.

171 (68.9%) IBD patients have been always pro-vaccine, while the others 77 decided after discussion with their own gastroenterologist (41, 53.2%), relatives (16, 20.8%), general practitioner (9, 11.7%) or according to mass-media (9, 11.7%). The reasons leading to be vaccinated were: duty of collective (190, 76.6%), back to the normality (91, 36.7%) and fear to get sick (71, 28.6%). The possibility to be vaccinated in their own IBD Centre was considered relevant by 141 (56.8%) IBD patients. After vaccine, 67 (27.0%) reported no concerns; the others reported the following: side effects in the short- and long-term (60, 24.2% and 62, 25.0%, respectively), IBD flare (22 (8.9%), interference with IBD medications (19, 7.7%) and inefficacy (18, 7.3%).

Conclusion

The majority of IBD patients accepted to be vaccinated against SARS-CoV-2. IBD patients who previously refused vaccine against influenza also refused vaccine against SARS-CoV-2. The possibility to be vaccinated in their own IBD Centre and, among undecided patients, the gastroenterologist recommendations played a relevant role towards the decision to be vaccinated.
P232 Depression and fatigue in active IBD from a microbiome perspective - a bayesian approach to faecal metagenomics
Authors: Thomann A , Wuestenberg T , Wirbel J , Zeller G , Thomann P , Knoedler L L , Ebert M , Reindl W
Published: January 2022

Background

Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease, potentially due to inflammation-mediated changes in the microbiota-gut-brain-axis.

The aim of this study was to investigate associations between structural and functional microbiota characteristics and severity of fatigue and depressive symptoms in patients with active IBD

Methods

We included clinical data of 62 prospectively enrolled patients with IBD in an active disease state. All patients were scheduled for a change in the therapeutic regime, and completed questionnaires and collected stool samples before induction of the new therapy. Based on taxonomical and functional metagenomic annotations of faecal gut microbiota, we investigated associations between bacterial genera/functional (KEGG-)modules and symptom severity of self-reported fatigue and depression by means of a bayesian triple association approach

Results

Triple associations with moderate to strong evidence were found for 3 genera (Odoribacter, Anaerotruncus and Alistipes) and 3 functional modules (pectin-, glycosaminoglycan- and central carbohydrate metabolism) with regard to depression (left), and for 4 genera (Intestinimonas, Anaerotruncus, Eubacterium and Clostridiales g.i.s) and 2 functional modules implicating amino acid and central carbohydrate metabolism with regard to fatigue (right).

Conclusion

This study provides first evidence of a triple association between microbiota composition, function and extraintestinal symptoms in active IBD. Depression and fatigue were associated with lower abundances of short chain fatty acid-producers and distinct pathways implicating glycan-, carbohydrate and amino acid metabolism. Our results suggest that microbiota-directed therapeutic approaches may reduce fatigue and depression in IBD and should be investigated in future research
P242 Latent Tuberculosis: frequency of occurrence and effect on clinical, laboratory, endoscopic and morphological activity of the course Inflammatory Bowel Diseases
Authors: Babayeva-Sadigova G , Makhmudov U , Asadova G , Quliyev F , Samadova T , Mirzazade O , Hasanova A
Published: January 2022

Background

Early diagnosis of tuberculosis remains challenging due to the nonspecific clinical manifestations that can mimic other gastrointestinal diseases and range from acute to chronic abdominal disease. In recent decades, latent tuberculosis (LTI) has been of particular interest. Patients with inflammatory bowel disease (IBD) are at risk of contracting tuberculosis.

Aim

to identify the incidence of LTI in patients with IBD and its effect on the clinical, laboratory, endoscopic and morphological activity of IBD.

Methods

The study included 350 patients with IBD, who were monitored and a group of patients (188 people (UC = 80, CD = 101, MC = 7) who did not respond / or poorly respond to basic IBD therapy were identified. In this group, the determination of the quantiferon test was carried out. To achieve this goal, two main hypotheses were considered: assessment of IBD-associated and systemic vascular lesions (h/s CRP, platelet count, homocysteine, vit D, urine albumin, fecal calprotectin and lactoferrin; α-TNF, IL-1,IL-2,IL-4,IL-6,IL-8,IL-10,IL-18; endoscopic examination with pathomorphological assessment), assessment of changes in the thickness of the vascular intima and blood flow velocity (based on the doppler determination of the pulse wave velocity (PWV) and the thickness of the intima media (CIMT) on the common carotid, vertebral and subclavian arteries).

Results

The number of positive responses to the quantiferon test was found in 37 patients (19.7%) / 10.6%) out of 188 patients (53.7%); positive skin tests (Mantoux reaction) ≥5 mm in 78 (22.3%) patients; altered peritoneal lymph nodes in 28 (8%), pulmonary and pleural TB in 9 (2.57%) patients. There were no patients with intestinal TB / “+” TB PCR in the gastrointestinal tract tissue. The prevalence of positive cases according to the quantiferon test was: in the general group of patients - 10.6%. Laboratory indicators for both IBD and systemic vascular lesions were higher in the group of patients with latent tuberculosis (Table 1, Table 2). Damage to the vascular bed (based on doppler determination of pulse wave velocity (PWV) and intimal thickness (CIMT) on the common carotid, vertebral and subclavian arteries) was more pronounced in the group of patients with latent tuberculosis (CIMT (mm) 0.68 ± 0, 1 / 0.67 ± 0.2; PWV (sm / s) 93.3 ± 2.2 / 97.2 ± 1.4).

Conclusion

Conclusion. Comparing the results of the data before and after the treatment of latent TB in patients with IBD, certain dependences of the influence of infection on the course of IBD (h/s CRP, platelet levels, homocysteine, fecal calprotetin and lactoferrin, IL-8 and a decreased vit. D; changes, associated with damage to the vascular bed), endoscopic and morphological activity.
P248 Lifestyle changes after Inflamatory Bowel Disease diagnosis
Authors: Belén Galipienso O , Cameo J , Bernabeu P , Mira C , García M D M , Pomares C , Muñoz D , Canales N , Gutierrez A , Zapater P , van-der Hofstadt C , Jover R , Ruiz M T , Sempere L
Published: January 2022

Background

Some lifestyle factors seem to modify the course and clinical outcomes in patients with Inflammatory Bowel Disease (IBD). A higher level of exercise has been associated with lower risk of relapse among patients in remission whereas obesity increases the risk of treatment failure. Moreover, sleep disturbances and stress have been associated with a higher risk of flare up. The relationship between various lifestyle factors and IBD seems to be bi-directional. In clinical practice, we observe lifestyle changes in patients with IBD unknowing exactly their incidence. The aim of this study is to assess lifestyle changes after IBD diagnosis.

Methods

Prospective and multicenter observational study in patients with new diagnosis of IBD. Semi-structured interviews were conducted evaluating lifestyle changes (diet, physical activity, rest, relaxation techniques, and leisure activities) in the first 6 months after IBD diagnosis.

Results

154 patients were included 79 (51.3%) Crohn’s disease (CD), 75 (48.7%) Ulcerative Colitis (UC). 68 (44.2%) women, 86 (55.8%) men. Mean age 42.5 years (±16.1). BMI 24.9 ± 5. 67 (43.5%) were never-smokers, 26 (16.9%) smokers, 61 (39.6%) ex-smokers. Lifestyle changes consisted in dietary modifications in 94 (61%) patients, increased physical activity in 43 (27.9%) patients, increased time for resting in 32 (20.8%) patients, the use of relaxation techniques in 11 (7.1%) patients and increased leisure activities in 27 (17.5%) patients. There were no differences in lifestyle changes between CD patients and UC patients except for the diet, which was more often modified by CD patients than UC patients [58 (73.4%) vs. 36 (48%) p=0.001, OR 95% 2.9 (1.5–5.8)]. Regarding differences between both sexes, men more frequently increased exercise than women [30 (34.9%) vs. 13 (19.1%) p=0.03 OR 95% 2.2 (1.07-4-7)]. There were no differences in rest, relaxation, leisure activities and dietary changes between men and women. Age was not associated with changes in lifestyle, except for leisure activities, which were more often increased in patients under 40 years of age than patients over 40 years of age [17 (23.9%) vs 10 (12%) p=0.053, OR 95% 2.2 (0.97–5.4)].

Conclusion

Lifestyle changes in IBD patients appear soon, and diet is the most frequently modified habit.
P252 Low adherence is associated with worse disease course in Ulcerative Colitis: a retrospective study from a single referral center
Authors: Viola A , Demarzo M G , Abbruzzese A , Chiappetta M F , Costantino G , Alibrandi A , Fries W
Published: January 2022

Background

New therapeutic approaches for ulcerative colitis (UC) are becoming available but still there is no robust evidence for predictors of poor outcome. We aimed to evaluate factors associated with a more aggressive UC course.

Methods

Data of all UC outpatients followed for at least 3 years after diagnosis were retrospectively collected. Demographic, anamnestic data, disease characteristics and treatment were collected. Disease patterns were defined according to the IBSEN study (Henriksen M. et al1). Disease worsening at 3 years was defined as the presence of disease extension at endoscopy, proctocolectomy and or early use of biologics. Risk factors for chronically active disease were assessed. Moreover, the following outcomes were explored according to disease extent at diagnosis (E1-E2 vs E3): corticosteroid free remission, hospitalization, early use of immunomodulators and biologics, colorectal cancer, adherence, mucosal healing at 3 years. Survival analysis was carried out to estimate the probability of receive a biological treatment within 3 and 5 years from diagnosis according to disease extent (E1 vs E2 vs E3) and disease patterns.

Results

A total of 345 UC patients were included and followed for a mean period of 94 months. Patients with extensive colitis had a higher rate of colectomy (p < 0.001), hospitalizations (p=0.004) and of chronically active disease 3 years after diagnosis (p < 0.001) and were more likely to receive early biologics and IMM (p= 0.04 and p=0.01 respectively) (Figure 1). The only factor associated with chronic active disease was non-adherence (p < 0.03; OR 0.49, 95% CI: 0.26–0.95) (Table 1). No differences were found for the probability to receive biologics within 3 and 5 years from diagnosis according to Montreal extension at diagnosis and disease pattern.

Conclusion

Patients diagnosed with pancolitis were more likely to underwent colectomy or to have a chronically active disease with a higher rate of hospitalization, early use of IMM or biologics. The only predictor for chronically active UC was the lack of adherence to therapy within the first 3 years after diagnosis.

Reference

1. Henriksen M, et al; IBSEN Study Group. Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study). Inflamm Bowel Dis. 2006;12:543–50.

The study was supported by a grant from Ferring S.p.A.
P253 Are we doing enough to prevent colectomy in Inflammatory Bowel Disease (IBD) patients? A 5-year review of colectomy rates in Shropshire and Mid-Wales UK (2015–2019)
Authors: Javed A , Butterworth J , Townson G
Published: January 2022

Background

Colectomy for IBD significantly impacts the psycho-social aspects & quality of life.

Methods

Electronic records were retrospectively analysed for colectomy rates & parameters of interest.

Results

68 patients (Men 37:Women31), median age 30 years had colectomies. Annual colectomy rates remained constant;7 (2015), 20 (2016), 11 (2017) & (2018) each and 19 (2019). 28% had colectomy within 1 year of diagnosis and only 63% received a biologic agent. Over half, (54%)had emergency surgeries & 37% experienced infections, re-laparotomy and ileus (20% each).

Conclusion

There is an opportunity to risk-stratify patients at diagnosis based on the risk factors (men, younger age, severe/extensive disease) to a top-down therapy & treat to target strategy to reduce colectomy rates.
P256 The practical use of an eHealth platform for inflammatory bowel disease patients: the validation of the IBD Tool web-based tele-monitoring system
Authors: Giuffrida E , Mangia M , Figini V , Carli E , Colombo A , Mendolaro M , Lavagna A , Lia C , Bonina M , Martínez De Carnero F , Morello E , Cosimato M , Rocca R , Pagna G , Daperno M
Published: January 2022

Background

Tele-monitoring and eHealth tools are useful to monitor disease burden and activity in inflammatory bowel disease (IBD). We developed a web-based tele-monitoring platform (IBD Tool), in order to monitor granularly disease activity and impact on patients’ lives. Aim of this abstract is to report preliminary data on IBD Tool effectiveness.

Methods

Consecutive IBD patients were offered the access to the tele-monitoring platform (IBD Tool) as a part of an ongoing investigator-initiated observational study, overall 677 patients were enrolled between February and November 2021. Validated questionnaires administered on the platform captured disease activity [Harvey Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI), Monitor IBD At Home Questionnaire for Crohn’s disease (CD) or for ulcerative colitis (UC): MIAH-CD or MIAH-UC] and disease burden and quality of life. Patients were randomized 1:1 to standard of care (only activity questionnaires required every 3-months) and telemedicine (activity questionnaires required monthly, remaining questionnaires every 3-months).

Results

Out of 678 patients enrolled, 585 (87%) are active on the platform and filled overall 14,297 questionnaires during an average follow-up of 9.8 months, the mean number of questionnaires filled/patient was 24.9. Characteristics of the patient enrolled in the study are presented in Table 1.

Table 1. Characteristics of patients enrolled on the IBD Tool tele-monitoring platform and questionnaires filled

Among the 320 cases with 2 or more observations in the IBD Tool platform, it was possible to analyse disease activity variation (summarized as constant, amelioration, or worsening) according to SCCAI or HBI changes ±2 points, results are detailed in Table 2.

Table 2. Charateristics of patients constant, ameliorating or worsening in time.

Conclusion

Patients’ persistence in the tele-monitoring system is adequate; the systems offer granular and precise multidimensional evaluation of IBD patients.
P266 Elderly-onset Inflammatory Bowel Disease: a retrospective single-center study with current follow-up
Authors: Dias E , Nunes A C R , Garrido I , Andrade P , Lopes S , Macedo G
Published: January 2022

Background

Elderly-onset inflammatory bowel disease (IBD) will be seen more frequently with the ageing of the population and the increasing incidence of IBD. However, to date there are few studies focusing in the medical management of IBD in this patient population. The aim of our study was to describe the main clinical features of elderly-onset IBD.

Methods

Patients diagnosed with IBD after the age of 65 years (elderly-onset IBD) until December 2020 with current follow-up in a specialized IBD consultation in a tertiary hospital center (by June 2021) were included in this retrospective study. The hospital electronic medical records were searched in order to retrieve demographic and clinical data of the patients.

Results

A total of 61 patients were included, with mean age of 72.0 years (range 65–86); 34 (55.7%) were male. All patients were alive and with current follow-up. Mean follow-up duration was 84 months (interquartile range 35–97). The most common type was ulcerative colitis in 36 (59%) patients, whereas Crohn’s disease was diagnosed in 25 (41%). Among patients with ulcerative colitis, 14 (38.9%) had pancolitis, 11 (30.6%) left-sided colitis and 11 (30.6%) proctitis. Crohn’s disease was most often ileal in 48% of patients, followed by colonic in 44% and only 8% of patients presented ileocolonic disease. Non-stenosing non-penetrating behavior was present in 19 (76%) patients, followed by stenosing behavior in 6 (24%), with no case of penetrating phenotype; associated perianal disease was detected in 5 (20%) patients. Salicylates were used as single maintenance therapy in 44 (72.1%) of all patients with IBD; 11 (18%) patients required immunosuppressant therapy with biological agents including infliximab (n=5), vedolizumab (n=5) or ustekinumab (n=1) whereas 4 (6.6%) patients required no specific treatment. Surgery was necessary in only 3 (4.9%) patients: 2 performed total colectomy for refractory ulcerative colitis, whereas the other required right ileocolectomy for stenosing Crohn’s disease. At the time of diagnosis, anemia was present in 23 (37.7%) patients. In 21 (34.4%), levels of C-reactive protein were significantly elevated (>10 mg/L) and hypoalbuminemia was present in 12 (19.7%). Vitamin D levels were measured in 44 patients, among these 41 (93.2%) presented abnormally low levels.

Conclusion

Patients with elderly-onset IBD appear to have a mild disease course, with low use of biological agents and surgery. Ileocolonic involvement and penetrating phenotype in Crohn’s disease appear to be rare. Nevertheless, other comorbidities are often present and IBD may contribute to a higher prevalence of laboratory abnormalities including anemia and vitamin D deficiency.
P272 Psychological burden in newly diagnosed IBD patients: Differences between Crohn’s Disease and Ulcerative Colitis in early IBD
Authors: Bernabeu P , Cameo J I , Gutiérrez A , García G , García M F , Aguas M , Belen O , Zapater P , Cabezos P , Andreu A , Jover R , van-der Hofstadt C , Ruiz M T , Sempere L
Published: January 2022

Background

Psychological factors such as stress, anxiety and depression are frequently related to IBD. However, there are few studies of these factors in patients with a new diagnosis of IBD. The aim of the present study is to test the psychological burden in patients with a recent diagnosis of IBD and to check if there are differences between Crohn’s disease (CD) and Ulcerative Colitis (UC).

Methods

Prospective, multi-center, observational study in patients with a new diagnosis of IBD (<6 months). The patients were recruited from 4 different Spanish hospitals. Patients were evaluated using the Holmes and Rae social readjustment rating (SRRS), the hospital anxiety and depression scale (HAD), Scale of Stress Perceived by the Disease (EAE) and quality of life questionnaire for patients with inflammatory bowel disease (IBDQ).

Results

We included 156 patients, 69 (44.2%) women and 87 men (55.8%); 80 (51.3%) CD and 76 (48.7%) UC, mean age 42.3 (SD 16.21) years. The sample was homogeneous between groups in relation to socio-demographic variables. In the total sample a 60.9% of the patient associated the onset of the disease with a stressful life event. Patients with CD showed a greater psychological impact on measures of anxiety, CD 48.8% - UC 25%, OR 2.8, (95% CI 1.4–5.6), depression CD 25% - UC 9.2%, OR 3.2 (95%CI 1.2–8.3) and stressful life events CD 86.3% - UC 67.1%, OR 3 (95%CI 1.3–6.8). In terms of general quality of life, 82.9% of UC patients showed high scores compared to 57.5% of CD patients, OR 0.27 (95%CI 0.13–0.58). In the IBDQ domains, CD patients had lower scores than UC patients, except in the digestive domain, where scores were similar. In the scale of perceived stress due to the disease, both groups showed elevated values (CD 86.3% - UC 80.3%).

Conclusion

Patients with a recent diagnosis of CD are more emotionally affected and have a poorer quality of life at the beginning of the diagnosis when compared to patients with UC. Both have high scores in perceived stress due to the disease. They perceive the disease at diagnosis as a highly stressful life event, so this should be considered to promote interventions (perhaps disease-specific) aimed at alleviating that stress and preventing it from interfering with the course of the disease.
P285 Longitudinal single cell transcription profiling of peripheral blood disentangles shared and biologic-specific patterns of early remission in active IBD patients
Authors: Bernardes J P , Mishra N , Schulte-Schrepping J , Herresthal S , Tran F , Aden K , Beyer M , Schultze J , Rosenstiel P
Published: January 2022

Background

IBD patients suffer from an uncertain disease course with only 10–20% of patients sustainably benefiting from complete and long-term remission, despite several modern biologic therapies being available. Large multi-omics datasets aimed to elucidate the relationship between changes in disease pathophysiology upon introduction of targeted therapy have delineated overal molecular pathways affected by biologic treatment (e.g. anti-TNF treatment). However, cell-specific molecular studies with the ability to detect cellular features associated with biologic treatment remain scarce, in particular, studies that focused on the mechanisms of action different biologic treatments and potential predictors of early therapy response.

Methods

We collected longitudinal single-cell RNA-seq data from 21 IBD patients treated with anti-TNF and anti-IL12/23 biologic treatments. The analysis included single-cell transcription profiles of PBMCs (>500,000 cells) collected before and two and six weeks after the first round of treatments. Cell-types of interest were identified by selecting changes in immune cell proportions and molecular patterns detected throughout the course of treatment. Specifically, we were interested in identifying molecular pathways that distinguish patients undergoing remission at 14 weeks of treatment (Partial Mayo score <2 or HBI <5).

Results

Upon anti-TNF therapy, most patients displayed an increase in the number of B cells, with patients with a favourable disease outcome most likely to display an increase in the proportion of memory and transitional B cells. Remarkably, for Crohn’s disease patients, transitional B cell proportion increased throughout the course of anti-TNF treatment, while it decreased for patients undergoing anti-IL12/23 treatment. Molecular signatures related to leukocyte and lymphocyte proliferation were shared at early time points of therapy response, but interestingly, the decrease was not sustained for patients not undergoing remission. Similar patterns could be identified for NF-κB and Toll-like receptor signaling pathways in memory B cells. Moreover, we identified a molecular cluster comprised of Fc receptor-like (FCRL) family members that might infer response to anti-TNF treatment even before the treatment has started, implying hyperactivity of B cells in inflammation as a determinant factor of therapy response.

Conclusion

Here, we identified cell-type specific molecular changes in the B cell compartment that are specific to the biologic treatment. Underlining the importance of comparative clinical studies in boosting the rates of patients with a high chance for long-term benefit, by stringent optimization of therapy and personalized treatment.
P310 Atopic dermatitis is associated with the clinical course of Inflammatory Bowel Disease
Authors: Kim K W , Ha H , Jun Y , Lee H J , Yoon H , Kang H W , Im J P , Kim J S , Koh S J
Published: January 2022

Background

There are a few studies about the relationship between inflammatory bowel disease (IBD) and atopic dermatitis (AD). It implicates that both diseases have common pathophysiologic mechanism and are able to affect each other. However, little information is available for the effect of AD on the clinical course of patients with IBD.

Methods

This is a retrospective, observational case-control study. Patients with concurrent IBD and AD were defined as case group and those with IBD only as control group. Diagnosis of AD was defined as chronic eczematoid dermatosis diagnosed by dermatologists. Age-, gender-, and IBD subtype-matched patients with a confirmed diagnosis of IBD were included as control group. The ratio of the case and control group was set as, 1:2. Trend in the duration from diagnosis of IBD to first use of biologics, first IBD-related operation and first IBD-related bowel resection were estimated with Cox regression analysis.

Results

The numbers of patients in the case and control group were, 31 and, 62, respectively. Compared with the control group, the case group showed an earlier disease onset (unit: years, 22.13 ±, 10.66 vs., 17.68 ±, 8.07, p = 0.043) and longer disease duration of IBD (unit: months, 98.37 ±, 69.24 vs., 150.77 ±, 83.45, p = 0.002). In addition, the proportion of biologics use (35% vs., 61%, p = 0.018) and the total numbers of biologics usages (0.48 ±, 0.76 vs., 1.06 ±, 1.12, p = 0.013) were higher in patients in the case group than those in the control group. In the Cox-regression analysis, there was a significant decrease of the duration for the biologics free survival in the case group compared with the control one after the adjustment with age, IBD subtype, onset age and disease duration (p < 0.001).

Conclusion

Patients having concurrent IBD and AD exhibited different characteristics compared with those having IBD only, particularly in terms of disease onset and severity. Furthermore, AD showed an significant effect on the time for the initiation of biologics. Further research is required to elucidate the common pathogenesis and the role of AD on the clinical course of IBD.
P314 Elderly onset is associated with low efficacy of anti-TNF treatment in Bio-naïve IBD patients: A multicenter cohort study by the Osaka Gut Forum
Authors: Amano T , Shinzaki S , Asakura A , Tashiro T , Otake Y , Tani M , Yoshihara T , Inoue T , Takehara T
Published: January 2022

Background

The number of elderly patients with inflammatory bowel disease (IBD) is increasing, but the outcomes of patients with elderly onset (EO) IBD treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD.

Methods

This was a multicenter retrospective observational study including bio-naïve patients with IBD who started anti-TNF treatment from, 2010 to, 2019 at, 18 hospitals of the Osaka Gut Forum. Elderly patients were defined as those, 60 years and older, and elderly patients with IBD were further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). The clinical symptoms were evaluated by partial Mayo score (pMayo) for UC and Harvey-Bradshaw index (HBI) for CD, and the clinical remission rate at, 52 weeks after the start of treatment was analyzed retrospectively. Clinical remission was defined as pMayo ≤, 2 and each subscore ≤, 1 for UC and HBI ≤, 4 for CD.

Results

A total of, 432 patients were enrolled, comprising, 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and, 352 under age, 60 (Non-elderly, 81.5%). After, 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and, 60.8%; P = 0.001, and, 35.9% and, 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission [Odds ratio (OR), 0.49, 95% confidence interval (CI), 0.25–0.96] and steroid-free remission [OR, 0.51, 95%CI, 0.26–0.99] after, 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly lower in Elderly-EO than in Non-elderly (P = 0.007), but comparable between Elderly-NEO and Non-elderly.

Conclusion

Anti-TNF treatment is less effective for bio-naïve EO-IBD than for elderly patients with younger onset and non-elderly, and may raise safety concerns in this group of patients.
P323 The Crohn’s Disease Exclusion Diet (CDED) for pouch inflammation: an interventional pilot study
Authors: Fliss Isakov N , Kornblum J , Zemel M , Hirsch A , Maharshak N
Published: January 2022

Background

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with UC. Unfortunately, pouchitis is a common condition, reported in up to, 72% of pouch patients. Pouchitis pathogenesis is not entirely clear and has similarities to that of Crohn’s disease (CD), given the de-novo inflammation of the small intestine, the microbial dysbiosis and the occurrence of a penetrating phenotype. The Crohn’s Disease Exclusion Diet (CDED) has demonstrated its efficacy in improving clinical and biochemical parameters of intestinal inflammation in CD. Therefore, we aimed to examine whether the CDED may be effective for the treatment of active pouchitis.

Methods

A non-controlled, open-label, interventional pilot trial. Active pouchitis patients were recruited at the comprehensive pouch clinic of the Tel Aviv Medical Center (TLVMC), a tertiary center. Patients were treated with the CDED (phases, 1–3) for, 24 weeks, underwent, 5 clinic visits (weeks, 0, 3, 6, 12 and, 24) which included physician assessment and monitoring [clinical pouch disease activity index (cPDAI) sub score evaluation], dietary evaluation and guidance, inflammatory biomarkers evaluation, and collection of biologic samples. Patients underwent three pouchoscopy procedures (baseline, end of phase, 2 and end of phase, 3) for assessment of endoscopic and histologic disease activity. The primary endpoint of the study was week-6 clinical remission (cPDAI subscore≥2).

Results

Fifteen patients (mean age, 42.6±11.2, 3 males, mean pouch age, 14.7±10.7 years) with pouchitis were recruited (Crohn’s like disease of the pouch, n=5; chronic pouchitis, n=4; acute pouchitis, n=3; recurrent acute pouchitis, n=3). Nine patients completed the study protocol and were evaluated throughout, 24 weeks, while six patients were withdrawn: four due to exacerbation requiring antibiotics, and two due to bowel obstruction. No other adverse events were noted. Clinical remission was achieved by, 66.7% of the study population at week, 6 by per-protocol analysis, and was maintained by, 60.0% at week, 12. Modified PDAI (mPDAI) decreased at week, 12 compared to baseline (8.0 vs., 5.0, P=0.027), with an improvement in the median number of defecations per day (24h) (12.5 vs., 7.0, P=0.003), and night (2.5 vs., 1.0, P=0.018). CRP and fecal calprotectin decreased compared to baseline (11.1±5.2 vs, 6.0±4.0, P=0.007, and, 697±680 vs, 497±483, P=0.607). Among patients who achieved clinical remission at week, 6, 80% maintained remission at week, 12 (P=0.025).

Conclusion

This pilot study demonstrates that CDED is a beneficial and safe therapeutic dietary intervention for pouchitis. Larger controlled trials should be performed in this population.
P324 Tacrolimus for induction of remission in refractory ulcerative colitis: a Cochrane systematic review
Authors: Gordon M , Sinopoulou V , Pana M , Moran G
Published: January 2022

Background

There is a limited number of treatment options for patients with corticosteroid refractory ulcerative colitis (UC). We aimed to evaluate tacrolimus for induction of remission in these patients.

Methods

MEDLINE, Embase, CENTRAL, Clinicaltrials.gov and ICTRP were searched up to October, 2021 to identify all relevant randomised contolled trials (RCTs). The authors independently reviewed potentially relevant studies to determine eligibility based on pre-specified criteria. A data extraction form was developed and used to extract data from included studies. Data were analysed using Review Manager. The primary outcomes were induction of remission and clinical improvement, as defined by the studies.

Results

Five RCTs were included with a total of, 347 participants with active UC. There is low certainty (oral and rectal) tacrolimus may be superior for clinical remission when compared to placebo (14/87 to, 1/61, RR, 3.76, 95% CI, 1.03 to, 13.73). There is low certainty (oral and rectal) tacrolimus may be superior for clinical improvement when compared to placebo (45/87 to, 7/61, RR, 4.47, 95% CI, 2.15 to, 9.29. The results on adverse events are of very low certainty and no conclusions can be drawn. There is low certainty there may be no difference in achievement of clinical remission when tacrolimus suppositories (16/44) were compared to beclomethasone (15/44) (RR, 1.07, 95% CI, 0.60 to, 1.88). There is low certainty there may be no difference in clinical improvement when tacrolimus suppositories (22/44) were compared to beclomethasone (22/44) (RR, 1.00, 95% CI, 0.66 to, 1.88). There is low cerainty there may be no difference in serious adverse events when tacrolimus suppositories (1/44) were compared to placebo suppositories (0/44) (RR, 1.00, 95% CI, 0.13 to, 71.70) and total adverse events (21/44 to, 14/44) (RR, 1.50, 95% CI, 0.88 to, 2.55). The evidence on the efficacy and safety of tacrolimus compared to cyclosporine is of very low quality and no conclusions can be drawn.

Conclusion

The cohorts studied are small, with missing data sets, short follow-up, and the clinical endpoints used are not in line with those suggested by regulatory bodies. No clinical practice conclusions can be made.This review highlights the need for further research that targets relevant clinical questions, uses appropriate trial methodology, and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration to capture the effectiveness of tacrolimus in the medium-to-long term. Well-structured efficacy studies need to be followed up by long-term phase, 4 extensions to provide key outputs and inform a real-world setting.
P328 In silico evaluation and pre-clinical efficacy of anti-TNF and anti-IL-23 combination therapy in Inflammatory Bowel Disease
Authors: Perrigoue J , Muniz-Bongers L , Ong L , Chen Y , Chang L , Ngo K , Stojmirovic A , O’Brien C , Germinaro M , Rao R , Vetter M , Towne J
Published: January 2022

Background

Despite advances in the treatment of inflammatory bowel diseases (IBD), fewer than, 40% of patients reach clinical remission, suggesting that improved response rates may require targeting of multiple pathogenic pathways through combination therapy. However, the rational selection of combination therapies based on patient and pre-clinical data remains a significant challenge.

Methods

Here, we used Crohn’s disease (CD) patient-derived molecular networks as a platform for bridging pre-clinical animal models of combination therapy to human disease. Intestinal transcriptional signatures of anti-TNF, anti-IL-23 or combination treatments were generated from the anti-CD40 agonistic antibody murine colitis model and the murine genes mapped to their human orthologues. Humanized gene signatures were intersected with human disease networks to generate treatment subnetworks and enrichment analyses performed.

Results

The anti-TNF subnetwork was enriched in genes expressed in myeloid cells, chemokine signaling and NFkB signaling, while the anti-IL-23 subnetwork was enriched in genes expressed in the intestinal epithelium, IL-17 signaling, and cell adhesion. The intersection of these two therapeutic gene signature subnetworks was significantly enriched in IBD GWAS loci genes and human CD inflammatory gene signatures, suggesting that the molecular mechanisms reflected in the pre-clinical model faithfully captures aspects of the human disease. Simultaneous inhibition of these two pathways could result in enhanced efficacy through targeting shared inflammatory pathways and complementary biology in myeloid and epithelial cells to reduce colitis. To test this hypothesis, mice were treated with varying doses of anti-IL-23, anti-TNF, or the combination of both. A synergistic response to combination therapy was observed both in reduction of systemic weight loss and inhibition of local colonic tissue inflammation by histopathology. A set of genes uniquely significantly modulated by the combination therapy compared to either monotherapy was mapped to our human IBD network. Upregulated gene networks in the combination therapy enriched in stromal cells, epithelial mesenchymal transition and extracellular matrix pathways, and adhesion pathways while downregulated gene networks were enriched in IBD disease signatures, M1 macrophages, neutrophils and IFN-γ signaling.

Conclusion

These results provide a novel, data-driven approach to predict effective combination therapies for inflammatory diseases and suggest that anti-TNF and anti-IL-23 combination therapy may drive more patients into deep remission through impacts on both shared and unique molecular pathways involved in IBD pathogenesis.
P332 Group-based Acceptance and Commitment Therapy (ACT) is acceptable and effective at reducing psychological distress in patients with Inflammatory Bowel Disease (IBD)
Authors: Duff A , De Petrillo A , Reynolds D , Bangura E , Pavilidis P , Mawdsley J
Published: January 2022

Background

ACT is a psychological therapy designed to increase psychological flexibility and improve how people relate to difficulties. It has been found to be efficacious with a range of difficulties (Gloster et al, 2020) but is increasingly used to support patients with long term health difficulties due to its unique perspective on the disease related and realistic ideas that patients hold about their conditions (Graham et al, 2016).

Initial studies using ACT with patients with IBD, have shown positive but varying effects on outcomes (Hou et al, 2017; Wynne et al, 2019). Feedback from these patients suggests that ACT is an acceptable approach (Dober et al, 2020), however, one trial had a significant drop out rate (Wynne et al, 2019). No real world evidence of the use of ACT with IBD patients has been reported and little is known about the practicality and efficacy as part of routine clinical practice

Methods

Those referred to a specialist IBD psychology service, 2019 to, 2021, were assessed as being suitable for an ACT based ‘managing symptoms group’. Those struggling with low mood, anxiety, chronic or functional symptoms and struggles with adjustment were included. Exclusion criteria were; trauma symptoms, interpersonal difficulties or individual issues such as surgery or adherence.

Patients attended, 8 weekly sessions of, 90 minutes. Data was captured on demographics and attendance. The primary outcome was adherence to the group, with completion defined as attending, 5 or more sessions. Secondary outcomes of psychological distress, flexibility and functioning, were measured with patient-reported questionnaires pre and post intervention. Descriptive statistics, t-tests and Wilcoxon rank tests were performed

Results

78 were assessed as suitable and enrolled for the group, 15 (19%) did not attend the first session and were discharged. Of the remaining, 63, 10 (16%) dropped out during the group, partial data is available for, 41 of those who completed the group and complete data for, 18 of these.

Conclusion

This is the first analysis of this type of intervention, performed in a clinical setting. Unlike a previous trial, the relatively low dropout and high number of sessions attended indicates that it is acceptable to the majority. Additionally, the significant change in psychological distress suggests that this group intervention is practical, effective and acceptable in settings where we are all under pressure for resources.

The results are from a small sample and suffered from typical challenges in obtaining patient-reported responses. However, there were no obvious differences between those who completed all measures and those who didn’t. The results provide evidence to support the continued use of ACT based interventions for those with IBD.
P334 Effectiveness and safety of ustekinumab in Crohn’s disease: short and long-term results of a multi-refractory cohort
Authors: Aparicio-Serrano A , Zamora Olaya J M , Ortiz Chimbo D S , Rodríguez Tirado M I , Gómez Pérez A , Soto Escribano P , Marín Pedrosa S , Iglesias Flores E , Benítez J M
Published: January 2022

Background

To evaluate the short and long-term effectiveness and safety of ustekinumab (UST) in a real-world multirefractory Crohn’s disease (CD) cohort.

Methods

An observational, retrospective and single-center study of CD patients treated with UST since June, 2017, with at least, 16 weeks of treatment. All patients were identified in the ENEIDA Registry. Demographic, disease, and outcome variables were collected. Clinical remission and response (measured by the physician global assessment and Harvey Bradshaw Index (HBI) score) as well as biological response (measured by C-reactive protein (CRP) and fecal calprotectin) were evaluated at weeks, 16, 26, 52 and at the end of the follow-up. Kaplan-Meier survival curves were performed to analyze drug persistence and multivariate analysis to identify predictors of response. Treatment-related adverse events were assessed.

Results

64 patients included, mean age of, 49 years (35–60), 56.2% men and CD duration of, 15.5 years (8–22)., 53% had ileocolic involvement and, 59% stricturing and/or penetrating disease., 40% presented perianal disease, 35% active smoking and, 33% patients had extraintestinal manifestations., 92.2% had prior failure to biologics (44% failed at, 1 and, 48.5% failed ³2) and, 9.4% had failed to vedolizumab., 57.8% required prior surgery for IBD., 40.6% initiated UST for treatment of postoperative recurrence. Baseline clinical activity was present in, 87.5% patients (60% moderate-severe activity). Rates of clinical remission, response and no response were, respectively, 40.7%, 47.5% and, 12% at week, 16;, 56.8%, 32.8% and, 10.3% at week, 26;, 60%, 30% y, 10% at week, 52. At the end of the follow-up, more than, 2/3 of patients (76.3%) had clinical response or remission (figure 1). Overall, a significant reduction of HBI score was observed from baseline to week, 16 and maintained at W26 and W52 (figure 2). Likewise, a biological response was observed with a significant reduction of CRP (baseline of, 26.7 mg/dL) at different times of evaluation (figure 3)., 74.9% continued with UST for up to three years (figure 4). In the multivariate analysis, the only independent factor associated with non-response was previous therapy with vedolizumab (OR:, 0.055 [IC95%:, 0.005–0.551], p=0.001). The safety profile was favorable; only, 2 patients (3.1%) stopped the drug due to side effects (arthralgias and bladder neoplasia).

Fig, 1. Remission, response, and no response rates.

Fig, 2. Evolution of HBI score from baseline to W52.

Fig, 3. Evolution of CRP from baseline to W52.

Fig, 4. Persistence of ustekinumab during the follow-up period.

Conclusion

UST is effective and safe in a real-life refractory CD cohort, with a persistence of the drug of, 75% at, 3 years. Previous vedolizumab therapy is associated with UST treatment failure.
P340 Risankizumab in Inflammatory Bowel Disease: Real World Experience from a Pre-Approval Access Program
Authors: Dawson P , Sharma E , Dart R J , Lim S , Anderson S H , Ray S , Mawdsley J , Irving P M , Samaan M A
Published: January 2022

Background

Risankizumab is a new generation monoclonal antibody which inhibits interleukin-23A. It has applications in several immune mediated inflammatory diseases including moderate-to-severe CD. Pre-approval access was granted for a cohort of patients who had active disease and prior use of all European licenced biologic therapies for CD. We aimed to define the effectiveness and tolerability of risankizumab in this real-world, treatment refractory cohort.

Methods

We performed a retrospective cohort analysis of prospectively maintained data for patients starting risankizumab between January and September, 2021. All patients received doses at four weekly intervals (IV, 600mg doses for CD and SC, 300mg doses for IBD-U). Clinical disease activity, biochemical activity and quality of life were measured using HBI, CRP and IBD-C scores, respectively. Study evaluations were made at baseline, weeks, 4 and, 12. Data were analysed in GraphPad prism and are described as median (range).

Results

Since January, 2021, 16 patients have started risankizumab. We included, 13 patients who had completed the, 12 week induction period at the time of submission;, 12 with CD and, 1 with IBD-U. Demographics are shown in Table, 1. The characteristics are consistent with a more aggressive phenotype with the majority of patients (9 (75%)) having perianal involvement as well as having either stricturing (5(42%)) or internal penetrating disease (3(25%)). Nine (75%) patients had undergone prior luminal surgery, 7 of whom still had stomas, therefore were not included in the analysis for HBI. Median HBI at baseline was, 5 (0–10) vs, 2 (0–8) at week, 4 and, 1.5 (0–2) at week, 12 and due to small patient numbers was not statistically significant. There was an improvement in IBD-C scores. Median IBD-C score at baseline was, 5 (0–14) vs, 11 (4–16) at week, 4 (p=0.034) and, 12 (2–16) at week, 12 (p=0.067). CRP decreased from, 12 mg/L (1–48) at baseline to, 8 mg/L (1–20) at week, 4 (p=0.23) and to, 6 mg/L (1–34) at week, 12 (p=0.022). Results are represented in Figure, 1. Two patients experienced mild headaches, no other side effects were reported. At initiation two patients were being treated with steroids; one has since discontinued and one has remained on steroids. No other patients initiated steroids. No patients discontinued risankizumab during the study period.

Conclusion

We present a heterogeneous cohort of patients with refractory CD despite multiple biologic mechanisms. Overall, there was a positive impact of risankizumab induction over a, 12 week period with respect to symptoms, quality of life and CRP, showing the effectiveness of risankizumab in this refractory cohort. We will follow up, and at week, 24 will objectively assess disease activity with cross sectional imaging and/or endoscopy.