bluuebunny/crossref_metadata_2025_split huggingface dataset:
P786 Induction of endoscopic response, remission and ulcer-free endoscopy with upadacitinib is associated with improved clinical outcomes in patients with Crohn’s disease
Authors: Panés J , Louis E , Bossuyt P , Joshi N , Lee W J , Lacerda A , Remple V , Xuan S , Loftus Jr. E V 
Published: January 2023

Abstract

Background
STRIDE-II guidelines recommend endoscopic healing as an important treatment goal in Crohn’s disease (CD). This study evaluated the association of achieving endoscopic outcomes at week 12 and clinical outcomes at week 52 of maintenance treatment in patients with CD treated with upadacitinib (UPA).

Methods
This post-hoc analysis evaluated data from two Phase 3 UPA induction (U-EXCEED and U-EXCEL) trials and the maintenance (U-ENDURE) trial in patients with moderate to severe CD. Patients who responded to 12-week induction therapy with UPA (45 mg per day [QD]) in U-EXCEED or U-EXCEL and received maintenance therapy with UPA (15 or 30 mg QD) up to 52 weeks in U-ENDURE were included. Clinical outcomes (CD activity index [CDAI] remission, CDAI response, steroid-free CDAI remission, high sensitivity C-reactive protein [hs-CRP] level ≤5 mg/L, and fecal calprotectin level [F-cal] ≤250 mcg/g), were evaluated at week 52 and compared between patients who achieved endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) at week 12 and those who did not using Chi-square test.

Results
Of 337 clinical responders included in the analyses, 152 (45.1%), 87 (25.8%), and 75 (22.3%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at the end of induction. Significantly more patients who achieved an endoscopic response at end of induction (vs those who did not) attained clinical outcomes at week 52 (CDAI remission, 52.0% vs 34.6%; CDAI response, 54.6% vs 39.5%; hsCRP ≤5 mg/L, 52.0% vs 30.8%; and F-cal ≤250 mcg/g, 42.1% vs 21.6%; P≤0.01, Table 1). Patients who achieved an endoscopic response vs those who did not at end of induction were also more likely to attain steroid-free CDAI remission (50.0% vs 30.9%) at week 52, (P≤0.05, Table 1). Similar findings were observed in patients who achieved endoscopic remission vs those who did not at end of induction (P≤0.01, Table 1). Significantly more patients attained CDAI remission (58.7% vs 37.7%), CDAI response (58.7% vs 42.7%), hsCRP ≤5 mg/L (58.7% vs 35.0%) and F-cal ≤250 mcg/g (50.7% vs 25.0%) at week 52, among patients who achieved ulcer-free endoscopy vs those who did not at end of induction (P≤0.05, Table 1).

Conclusion
Achieving endoscopic outcomes at end of induction is associated with meaningful improvement in symptoms and inflammatory biomarkers at 52 weeks for patients with CD receiving UPA therapy. Endoscopic remission and ulcer-free endoscopy are associated with very similar long-term benefits.
P789 Inflammatory Bowel Disease subgroups identified by longitudinal faecal calprotectin profiles: A 10-year retrospective analysis of the Lothian IBD Registry
Authors: Constantine-Cooke N , Monterrubio-Gómez K , Plevris N , Derikx L A A P , Lyons M , Jenkinson P W , Gros B , Jones G R , Vallejos C A , Lees C W 
Published: January 2023

Abstract

Background
Faecal calprotectin (FCAL) is routinely used to monitor mucosal inflammation, and high FCAL values are associated with poor outcomes in IBD.
Having previously found clusters characterised by distinct FCAL profiles in a Crohn’s disease (CD) cohort of 356 subjects, we aimed to extend this approach to all IBD patients treated by the Edinburgh IBD Unit.

Methods
Subjects were required to have a diagnosis of IBD, three FCAL measurements within ten years of diagnosis between January 2005 and September 2019, and be treated by the Edinburgh IBD Unit. All FCAL was measured on the same ELISA essay as part of routine clinical care.
Latent class mixed models, an extension of linear mixed effects models with cluster specific fixed effects, were used to model and cluster FCAL trajectories. Fixed and random effects were modelled using natural cubic splines, which allows flexible models with relatively low computational cost when compared to high degree polynomials. Akaike information criterion, Bayesian information criterion and alluvial plots were used to decide on the appropriate number of clusters.
CD subjects were modelled independently of UC and IBDU subjects, with similar clusters across disease subtypes given the same numbering for ease of comparison. Hereafter, we will describe the UC and IBDU patients collectively.

Results
1,214 CD and 1,194 UC/IBDU subjects met the inclusion criteria. Across follow-up, 10,503 (median 7 per subject) FCAL measurements were available for patients with CD and 7,495 (median 5 per subject) for those with UC/IBDU.

Figure 1. Log-transformed ten-year faecal calprotectin profiles for Crohn’s disease subjects. Red curves demonstrate overall profile for each cluster. The blue dotted lines indicate an FCAL of log (250 μg/g), the commonly accepted threshold for biochemical remission.
For CD, six clusters were found to be appropriate, whereas five clusters were found to be the most appropriate for UC/ IBDU.
The overall cluster prmofiles were remarkably similar between CD and UC/IBDU. Both CD cluster 2 and UC cluster 2, the largest clusters, were characterised by consistently high FCAL across follow-up: remaining above the 250 μg/g threshold commonly used for biochemical remission (blue dotted lines in the figures).

Figure 2. Log-transformed ten-year faecal calprotectin profiles for ulcerative colitis subjects

Conclusion
After grouping CD and UC/IBDU subjects in a large cohort by their 10-year FCAL trajectories, we found remarkably similar trajectories across the two groups. In both cases, we found a large cluster of subjects with consistently elevated FCAL, which warrants further investigation.
P794 Effectiveness of administering zinc acetate hydrate to patients with inflammatory bowel disease and zinc deficiency: a retrospective observational two-center study
Authors: Sakurai K , Katsurada T , Aoyama K , Fukushima S , Onishi R , Yagisawa K , Nishimura H , Ito T , Furukawa S , Maemoto A , Sakamoto N 
Published: January 2023

Abstract

Background
Inflammatory bowel disease (IBD) patients frequently have zinc deficiency and that IBD patients with zinc deficiency are at higher risk for IBD-related complications and surgery. We reported the efficacy of zinc replacement therapy for IBD patients with zinc deficiency at ECCO2020, and now we report the results of our analysis with an extended observation period and an additional number of patients.

Methods
IBD patients with zinc deficiency who received zinc acetate hydrate (ZAH) from March 2017 to November 2021 were registered in this 2-center（Hokkaido University Hospital and Sapporo Higashi Tokushukai Hospital）, retrospective, observational study.

Results
One hundred twenty patients with Crohn’s disease (CD, n=82) or ulcerative colitis (UC, n=38) were registered.
Median serum zinc level and CDAI in CD patients significantly improved (59.0-92.3 μg/dL, P&lt;0.001; 118-86, P&lt;0.001, respectively) 4 weeks after ZAH administration. Similarly, median serum zinc levels and CDAI significantly improved (58.5-82.0 μg/dL, P&lt;0.001; 96-78, P&lt;0.001, respectively) 20 weeks after ZAH administration. In the 18 patients who underwent endoscopy both within 4 weeks before and within 60 weeks after ZAH administration, median SES-CD improved from 11.5 to 5.5 (P&lt;0.001). Logistic regression analysis identified “serum zinc level ≥52 μg/dl before ZAH administration” as a factor contributing to normalization of serum zinc concentration and “CDAI ≥96 before ZAH administration” as a factor contributing to improvement of disease activity.
Median serum zinc level and partial Mayo scores (PMS) in UC patients significantly improved (63.0-94.0μg/dL, P&lt;0.001; 2-0, P=0.002, respectively) 4 weeks after ZAH administration. Median serum zinc levels significantly improved (62.0-100.0μg/dL, P&lt;0.001) 20 weeks after ZAH administration, but no significant changes in PMS were observed. In the 12 patients who underwent endoscopy both within 4 weeks before and within 60 weeks after ZAH administration, median UCEIS improved from 5 to 3 (P=0.004).
Logistic regression analysis identified “dose of ZAH ≥75 mg/day” as a factor contributing to normalization of serum zinc concentration and “serum zinc level ≥65 μg/dl before ZAH administration” as a factor contributing to improvement of disease activity.
In both CD and UC, there was a significant correlation between serum zinc level and CDAI, CRP, and serum albumin level before ZAH administration.

Conclusion
ZAH administration to IBD patients with zinc deficiency is effective in improving zinc deficiency and may contribute to improving disease activity in IBD.
P796 Effectiveness and safety of ustekinumab for patients with ulcerative colitis: A single-centre retrospective study
Authors: Kimura M , Shimizu M , Shirai M , Sakaguchi Y , Kobayashi K , Iruya R , Seki S , Naitou D , Nishimiya T , Oouchi Y , Shibamoto M , Iwashita H , Miyamura M , Kikuchi H , Yamada A , Nakamura K , Matsuoka K 
Published: January 2023

Abstract

Background
Ustekinumab, a monoclonal antibody directed against the interleukin 12/23 p40 subunit, was approved worldwide in 2020 for the treatment of ulcerative colitis. The efficacy of ustekinumab in inducing and maintaining remission in moderate to severe ulcerative colitis was demonstrated in the phase 3 clinical study, the UNIFI trial; however, real-world data on the effectiveness and safety of ustekinumab for patients with ulcerative colitis is still scarce. We aimed to investigate the real-world effectiveness and safety of ustekinumab in patients with ulcerative colitis.

Methods
This was a single-centre retrospective study enrolling patients with ulcerative colitis who were aged 16 years or more and administered ustekinumab between March 2022 and March 2022 at Toho University Sakura Medical Center, a tertiary center. Data were extracted by chart review. Ustekinumab was administered as a single intravenous infusion (approximately 6 mg/kg) followed by 90mg subcutaneous injection at week 8 and then by 90mg subcutaneous injection every 8-12 weeks. The endpoints were 1) the proportion of patients achieving symptomatic remission, defined as a rectal bleeding score of 0 and a stool frequency score of 0 or 1 in patient-reported outcome-2 (PRO-2), at week 8, 2) time to discontinuation, and 3) safety during the observation periods.

Results
We enrolled 53 patients in this study, with a median age of 45 years (interquadrant range: 27-57). Thirty patients (56.6%) were male and 23 (43.4%) were female. The majority of patients (n=39; 73.6%) had extensive colitis. Notably, 21 (38.9%) patients were naïve to advanced therapies. Thiopurines had been administered to 24 (45.3%) patients. Twenty-one (39.6%) patients achieved symptomatic remission at week 8 after a single intravenous infusion. The proportion of patients with symptomatic remission was numerically higher in advanced therapy-naïve patients compared with advanced therapy-experienced patients (47.6% versus 34.4%) (Figure 1). Univariate analysis failed to identify clinical predictors for symptomatic remission at week 8. The time to discontinuation were significantly longer in advanced-therapy naïve patients compared with advanced therapy experienced patients, with a median observation period of 296 days (Figure 2). As for safety, one patient discontinued ustekinumab due to skin disorder. One death due to pneumonia was observed, which was unrelated to ustekinumab.

Conclusion
Ustekinumab was effective and safe in the real-world setting. Advanced-therapy naïve patients were more likely to continue ustekinumab compared with advanced therapy experienced patients.
P806 Perianal Crohn’s Disease (pCD): The outcome of 2nd line and 3rd line biologics in perianal Crohn’s disease
Authors: Shani U , Ben Shabat N , Klang E , Ungar B , Ben-Horin S , Kopylov U 
Published: January 2023

Abstract

Background
Treating perianal Crohn’s disease (pCD) is challenging with at least 60% of the patients not responding or relapsing after a year of 1st line biological therapy. Effectiveness data on 2nd and 3rd line in pCD is still quite limited. The aim of this study was to describe the effectiveness of 2nd and 3rd line biological therapy in pCD.

Methods
A retrospective cohort study of patients with pCD from a large tertiary center registry. We included all patients with pCD that were treated with &gt;1 biologic while anti-TNF was the first one used. Primary outcome was defined as clinical failure of 2nd or 3rd line treatment (as defined by the clinician) or radiological evidence for disease progression by MRI or transrectal ultrasonography (TRUS). Secondary outcomes were relapse of perianal fistula or abscess.

Results
Registry included 893 patients with pCD who are being followed up routinely in a dedicated IBD clinic; 643 patients received 1 biological were excluded. Final cohort included 245 patients treated with ≥2 biologics.
In 2nd line, 40/245 patients (16%) treated with infliximab (IFX), 128/245 (52%) with adalimumab (ADA), 48/245 (20%) with vedolizumab (VDZ) and 32/245 (13%) with ustekinumab (UST). 7/32 patients (22%) treated with UST failed the treatment, compared to 32/40 (80%), 101/128 (79%) , 37/48 (77%) patients treated with IFX, ADA and VDZ, respectively [Hazard Ratio(HR) 0.27 (0.1-0.69)]. Median time of 2nd line treatment with UST, anti-TNFs and VDZb was 2.5 (IQR=1-3[uk1] ), 3 (IQR=1-5) and 3 (IQR=1-4) years, respectively. Higher response rate in 2nd line therapy was associated with longer response duration to 1st line [OR (1.11-1.55), p&lt;0.001)].
99/245 patients (40%) required 3rd line treatment (VDZ - 52/99 , UST - 47/99 (48%)) patients). 8/47 patients (17%) under UST therapy experienced clinical failure, compared to 41/52 (78.8%) patients treated with VDZ [HR 0.32 (0.12-0.68)]. Median duration (years) of third line treatment with both UST and VDZ was 3 years (IQR=3-1).
Figure A shows Kaplan-Meier survival analysis to 2nd line and 3rd line failure.

Conclusion
2nd and 3rd line biological therapies may be efficacious in pCD patients. Ustekinumab appears to be effective as a 2nd or 3rd line treatment. Longer duration of treatment is associated with a higher likelihood of response to 2nd line treatment.
P815 Diet, nutrition, and the multidisciplinary approach in adults with Inflammatory Bowel Disease
Authors: Playford C , Asghar Z , Armstrong S , Ngomba R , Rochford A 
Published: January 2023

Abstract

Background
Patients with Inflammatory Bowel Disease (IBD) may associate dietary triggers with symptoms and even relapse of the disease, yet this is rarely acknowledged and included in treatment plans. Patients often self-impose dietary restrictions and manipulate their diet which can have significant health complications including nutrient deficiencies and malnutrition1. This often leads to a worse disease state, poorer clinical outcomes, and a reduced quality of life for these patients2.

Methods
A self-administered survey was digitally created with Crohn’s and Colitis UK (CCUK) and advertised through the CCUK website and their social media accounts. Patients with IBD aged ≥18 years were identified through convenience sampling. Those who were three months peri-operative or had a stoma were excluded from the study as their nutritional needs and experiences were likely to be more complex. Statistical Package for Social Sciences (version 27) was used for statistical analysis. A P-value of &lt;0.05 was considered statistically significant.

Results
267 participants completed the survey, 77.5% were female, 30% of participants were aged 36-45 years and 53.9% had Crohn’s disease. 44.9% of participants had been diagnosed with IBD for &gt;10 years. 90% of participants believed that food impacted on their disease at least some of the time. 77% reported that dietary therapy may be useful in managing their disease (P-value &lt; 0.001). Table 1 highlights where patients with IBD source dietary information. 93% of patients report a ‘trial and error’ approach to dietary manipulation to reduce their symptoms. Access to formal dietetic advice is extremely limited and reported by only 13% of participants. The majority of participants (78.7%) reported that a multidisciplinary approach was ‘very important’ in IBD care despite 68.2% reporting no access to a multidisciplinary team (P-value = 0.006).
Table 1. Sources of IBD dietary information

Conclusion
Diet plays an important role in the disease course for patients with IBD; however, our respondents reported poor dietary support from healthcare professionals. This may lead to unsupervised dietary restrictions based on poor sources of information that can cause or worsen nutrient deficiencies and lead to adverse health outcomes. Patients with IBD should have access to high quality dietary advice to help manage the disease.
References:
1. Nazarenkov N, Seegar K, Beekan L, et al. Implementing dietary modifications and assessing nutritional adequacy of diets for Inflammatory Bowel Disease. Gastroenterology & Hepatology. 2019; 15: 133-144.
2. Balestrieri P, Ribolsi M, Guarino M, et al. Nutritional aspects in Inflammatory Bowel Disease. Nutrients. 2020; 12: 1-11.
P817 Symptoms of COVID-19 in Patients with Immune Mediated Inflammatory Diseases
Authors: Schlosser T , Krasselt M , Elsing L , Hecker M , Holler B , Hoffmeister A 
Published: January 2023

Abstract

Background
Pandemic situation of the novel coronavirus disease (COVID-19) represents a challenging condition with a plethora of aspects. Symptoms of patients with immune mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD) and different rheumatic diseases are not well described.

Methods
We conducted a prospective questionnaire-based study (04/2022 – 10/2022) at our university medical center. Outward patients over the age of 18 years were screened. Participating patients reported about their individual COVID-19 history during pandemic′s course.

Results
In the end, 156 patients were willing to participate. Vast majority of the cohort had an established diagnosis of inflammatory bowel disease (117 [75%] vs. 39 [25%] patients with rheumatic disease). Eightyone patients (51%) self-reported about their COVID-19 infection. Diagnosis had usually been established by positive PCR. In general, courses of infection were mild: Only two patients (2% of patients with reported COVID-19) were hospitalized due to COVID-19 with one of the two needing intensive care. Asymptomatic COVID-19 had been described by 7 persons (9% of patients with reported COVID-19). Acute COVID-19 was accompanied by fatigue/tiredness in 58 persons (72% of patients with COVID-19) as most frequent symptom. Other complaints were common cold (55 patients = 68%), cough (51 patients = 63%), headache (44 patients = 54%) and fever (35 patients = 43%). Joint respectively muscle pain was a symptom of eight respectively nine patients with rheumatic IMID (=33%/38% of 24 self-reported COVID-19). Five rheumatic patients (21%) presented diarrhea as complaint due to COVID-19. In the IBD subgroup 15 patients (27% of 57 self-reported COVID-19) had this complaint. Painful joints were mentioned in 23 IBD patients (41%). Aching muscles occurred in 19 IBD patients (34%).

Conclusion
Discrimination between symptoms of COVID-19 in contrast to chronic IMID condition can be difficult as complaints might be overlapping.
P822 The negative impact of mental health comorbidity in children and young adults with inflammatory bowel disease: a UK population-based cohort study
Authors: Cooney R , Barrett K , Russell R K 
Published: January 2023

Abstract

Background
Whilst the high burden of mental health comorbidity in people with inflammatory bowel disease (IBD) is now being recognised, less is known about the additional impacts of having concurrent IBD and a mental health condition, especially in children and young adults.

Methods
We conducted a retrospective, observational study using a large UK primary care dataset (Optimum Patient Care Research Database). Children and young adults (aged 5-25 years) diagnosed with IBD prior to 2015 were identified and grouped into those with and without prevalent mental health conditions (any of depression, anxiety, eating disorders, body image disorder, attention-deficit disorder, behavioural disorders, adjustment disorder, acute stress disorder, schizophrenia, bipolar disorder or post-traumatic stress disorder). The following outcomes were compared over 5 years in the two groups; quality-of-life indicators (bowel symptoms [abdominal pain, discomfort or bloating, diarrhoea], systemic symptoms [fatigue, sleep problems, weight-loss, underweight, growth retardation], emotional function [low mood, substance abuse, deliberate self-harm, suicidal attempt or parasuicide] and social function [absence from school, absence from work, unemployment]), IBD-specific therapy interventions (diet [nutritional supplements], medications [oral and rectal 5-aminosalicylic acid and steroids, antimetabolites and tumour necrosis factor inhibitors] and surgery [abdominal and stoma formation]), and healthcare utilisation (primary care interactions and hospital admissions). Adjustment for confounders was performed using Cox regression for non-recurring outcomes (e.g. stoma formation), and negative binomial or Poisson regression for outcomes with recurring events (e.g. primary care interactions).

Results
1,943 individuals with IBD were identified. 295 of these had a prevalent mental health condition. Mental health comorbidity was associated with increased bowel symptoms (adjusted Incident Rate Ratio [aIRR] 1.82; 95% Confidence Interval [CI] 1.33, 2.52), sleep disturbance (adjusted Hazard Ratio [aHR] 1.63; 95% CI 1.02, 2.62), substance abuse (aHR 3.63; 95% CI 1.69, 7.78), primary care interactions (aIRR 1.33; 95% CI 1.12, 1.58) and hospital admissions (aIRR 1.87; 95% CI 1.29, 2.75) (Figure 1). In those &gt;18 years old, mental health comorbidity was associated with increased time off work (aHR 1.55; 95% CI 1.21, 1.99) (Figure 1).

Conclusion
Mental health comorbidity in children and young adults with IBD is associated with increased IBD symptoms, healthcare utilisation and time off work. Given the impact of mental health comorbidity, it is crucial those affected are monitored and receive appropriate mental health support as part of their multidisciplinary care.