bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.