Introduction

Adults with Crohn’s Disease (CD) may have dietary restrictions, micronutrient inadequacies and impaired health-related quality of life. With limited dietetic resources typically directed towards those with intestinal failure, overt malnutrition or active disease, there is a need to screen all patients to identify those at risk of nutritional issues for further assessment and support. Traditional methods of identifying nutritional risk focus on weight and BMI, and do not take account of factors related to IBD such as gastrointestinal symptoms that may limit food intake.

Aims & Methods

The INTICO2 study aimed to characterise the nutritional risk factors and nutritional status of adults with CD during disease remission. 196 adult CD outpatients in clinical and biomarker remission were recruited from a single centre UK IBD centre outpatients (Harvey Bradshaw Index<5 and calprotectin<250µg/g) as part of the INTICO2 observational study. Subjects needed to be in intestinal continuity and not under current dietetic care or treatment. Assessments comprised of a 7-day electronic food diary and a single time-point assessment of body composition (Bioelectrical Impedance), functional measurement (hand grip). Dietary impact factors (DIF) were captured using a novel patient-completed questionnaire. The questionnaire aimed to capture 1) weight loss 2) appetite using Simplified Nutritional Appetite Questionnaire¹(SNAQ) 3) restricted foods 4) disease specific factors 5) symptoms of micronutrient deficiencies.

Results

Subjects reported a mean of 4 (SD 3) DIFs, with 92% (180/196) of the cohort reporting at least 1 DIF. Food restriction was reported by 34% (67/196) of patients, with the most restricted foods being dairy, wheat, red meat, pulses, garlic and onion. In total, 47 separate food items were reported as being avoided, with a mean of 2 foods avoided per participant. Food diary analysis revealed dietary micronutrient inadequacy to be common with a mean of 6 (SD 4) nutrients below LRNI per subject. Impaired appetite (SNAQ ≤14) was reported in 30% (57/192) of participants; mean SNAQ 15.45±2.29. IBD risk factors and physical manifestations of nutritional issues DIFs are described in Table 1.

Table 1. IBD risk factors and physical manifestations of nutritional issues

Conclusion

Potentially undiagnosed nutritional issues were reported by patients completing the questionnaire. DIFs such as food restriction and impaired appetite appear to be evident in these adults with CD during clinical remission which may be associated with inadequate micronutrient intake when assessed by dietary analysis and lower fat free mass and muscle function. Developing a structured approach to exploring DIFs by a self-reported questionnaire may help identify individuals who may require a dietetic assessment.

References

1. Wilson MM, Thomas DR, Rubenstein LZ, Chibnall JT, Anderson S, Baxi A, Diebold MR, Morley JE. Appetite assessment: simple appetite questionnaire predicts weight loss in community-dwelling adults and nursing home residents. Am J Clin Nutr. 2005 Nov;82(5):1074-81. doi: 10.1093/ajcn/82.5.1074. PMID: 16280441.

Disclosure

INTICO2 is an investigator-led collaborative research program funded by Nestle Health Sciences

Introduction

Immunomodulators and biologicals play an essential role in current IBD management, but are associated with increased risk of infections. In light of the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. Post-marketing surveillance studies are pivotal to assess infection risk, yet mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. However, mild and moderate infections take longer to clear in immunosuppressed patients, have been reported to be the most burdensome adverse drug reaction according to patients, and can negatively influence drug adherence.

Aims & Methods

Aim: To assess the incidence of all infections and identify risk factors for the development of infections in IBD patients.
Methods: We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. [1] The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients and using the PRIQ which was implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for infections.

Results

In total, 629 IBD patients (n=346 CD, n=283 UC, 58.3% female, mean age at cohort entry 48.3 years [SD 14.8], mean disease duration 12.4 years [SD 10.8]) were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up. This resulted in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively. Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections types, respectively (Table 1). Compared to patients without treatment, patients on immunosuppressive treatment more frequently experienced infections of any severity (mild vs. no treatment: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p<0.001, moderate vs. no treatment: IRR 1.42 [95%CI 1.20-1.69] p<0.001). On multivariable logistic regression, female sex (mild adjusted odds ratio [aOR] 1.96 [95%CI 1.38-2.79]; moderate aOR 1.71 [95%CI 1.15-2.54]), smoking status (mild aOR 1.66 [95%CI 1.15-2.41]; moderate aOR 1.86 [95%CI 1.05-3.28]), higher BMI (moderate aOR 1.05 [95%CI 1.02-2.00]), and more comorbidities (mild aOR 2.41 [95%CI 1.46-3.98]; moderate aOR 1.82 [95%CI 1.07-3.11]) were all significantly associated with the development of mild and moderate infections.

Conclusion

​In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.

References

[1] Rezazadeh Ardabili A, van Esser D, Wintjens D, et al. Development and validation of a remote monitoring tool for assessment of mild, moderate, and severe infections in Inflammatory Bowel Disease [published online ahead of print, 2023 Feb 16]. J Crohns Colitis. 2023;jjad023. doi:10.1093/ecco-jcc/jjad023

Disclosure

M.P. reports grants and non-financial support from Falk Pharma, grants from European commission, grants from ZonMw (Dutch national research fund), grants and non-financial support from Takeda, grants and non-financial support from Johnson and Johnson, grants and non-financial support from Abbvie, non-financial support from Ferring, non-financial support from Immunodiagnostics, non-financial support from MSD, all outside the submitted work. D.J. reports grants from Top Knowledge Institute (Well on Wheat), grants from Horizon 2020 DISCOvERIE, grants from NWO-CCC Partnership program (Carbokinetics), all outside the submitted work. Z.M. reports grants form MLDS, Niels Stensen Fellowship and Galapagos. A.v.B. has served as speaker, adviser and/or principal investigator for AbbVie, Arandal, Arena, Celgene, Ferring, Galapagos, Janssen, MSD, Pfizer, Roche, Takeda, TEVA, and received research grants from Pfizer, TEVA, Eurostars funding, ZonMw, all outside the submitted work.
The other authors have nothing to disclose relevant to this publication.

Introduction

Ulcerative proctitis (UP) is an uncommon presentation in paediatric patients with ulcerative colitis, accounting for <10% of cases in most studies. Therefore, there is limited data on the clinical features and outcomes of these paediatric patients.

Aims & Methods

We aimed to characterize the clinical features and natural history of UP in children, and identify predictors of poor outcomes in a retrospective cohort study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged<18 years diagnosed with UP between 01/01/2016-31/12/2020. Associations between baseline characteristics at diagnosis of UP and different clinical outcomes were evaluated using univariable and multivariable Cox regression.

Results

Data were collected from 196 patients (median age at diagnosis 14.5 [IQR 11.9-15.9] years, 105 females [53.6%]). The most common presenting features were bloody stools (95%), abdominal pain (60%) and diarrhea (47%). The median Pediatric Ulcerative Colitis Activity Index (PUCAI) score at the time of diagnosis was 25 (IQR 20-35), with only 2 patients (1.1%) presenting with acute severe colitis (ASC). 125 patients (67.9%) had a PUCAI score of <35, reflecting mild clinical disease activity. Nevertheless, the majority of patients exhibited moderate-severe endoscopic inflammation, with a Mayo score of 2 in 103 (54.2%) and 3 in 40 (21.1%) patients. Most patients had normal inflammatory markers and albumin levels and the median fecal calprotectin value was 645 (IQR 238-1435) mcg/g, with 13/132 (9.8%) and 28/132 (21.2%) having a level of <100 mcg/g or <250 mcg/g, respectively. By the end-of-induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 52%, 50% 73%, respectively.
The median time to last follow-up was 2.7 (IQR 1.7-3.8) years. The rates of treatment escalation to oral steroids, thiopurines and biologics at 1, 3 and 5 years were 17.6%, 32.6% and 57.8%, 9.8 %, 24.3% and 43.2%, and 10.4%, 22.0% and 42.8%, respectively. Subsequent episodes of ASC were uncommon, involving up to 20% of the patients within 5 years of diagnosis. Nevertheless, IBD-related admissions were frequent, reaching 11.3%, 23.2% and 33.7% within 1, 3 and 5 years from diagnosis, respectively. Finally, only 6 patients (3.1%) had a colectomy by the end of follow-up. On multivariable cox regression analysis, only the PUCAI score was associated with poor outcomes, with a score ≥35 providing increased risk, including escalation to biologics (HR 3.5 [95% CI 1.8-6.6, P<0.001]), subsequent ASC event [HR 2.7 (95% CI 1.3-5.7, P=0.009]) and IBD-associated admission (HR 2.3 [95% CI 1.2-4.2, P=0.008]).
48% of patients that presented with UP and were rescoped exhibited proximal disease progression during follow-up. The presence of cecal patch at the diagnostic colonoscopy was more frequent in patients that subsequently exhibited proximal disease progression (4/58 [6.9%]) vs 11/51 [ 21.6%], [P=0.027).Moreover, the PUCAI score at the end-of-induction was significantly higher in patients that had subsequent disease progression.

Conclusion

This is the largest cohort, to date, of paediatric patients with UP. Children with UP exhibit high rates of proximal disease extension and requirement of systemic immunosuppressive medications, in the first years after diagnosis. Providers should consider to apply treat-to-target approaches, similar to other patients with UC, in the care of these patients with repeated sigmoidoscopies to document mucosal healing and a specific focus on quality-of-life measurements.

Disclosure

DES received payment or honoraria for contracts from Abbvie, lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Dr. Reddy’s, Montavit, Noventure, Nutricia, and Reckitt Benckiser, support for attending meetings from Nestle, not related to this study; KLK received consulting fees from Abbvie, Biocodex and Tillots pharma and a grant from Pediatric Research Foundation (Finland) and aa grant from Helsinki University Hospital Research Fund; DSS received consulting fees from AbbVie and a research grant from Takeda.

Clinical Case Summary

A 50 year old paraplegic gentleman (secondary to a road traffic accident) with a diversion colostomy and preserved small bowel length, and a history of idiopathic cirrhosis, was admitted with a one week history of high output stoma. Initially felt to be infectious, he was resuscitated with volume and electrolyte replacement. Despite a negative infection, autoimmune and extended inflammatory screen, the high stoma output persisted between 4-6L per 24 hours. He subsequently developed circulatory failure due to volume losses and required intensive care support for fluid management, parenteral nutrition (PN) and inotropes. Serial cross sectional imaging showed oedematous jejunal and ileal bowel without evidence of vascular insufficiency.

His stoma output failed to respond to maximum doses of loperamide, octreotide, proton pump inhibitors or opiates. He was commenced on a trial of high dose steroids without any benefit. A colonoscopy showed grossly oedematous bowel, with biopsies demonstrating preserved crypt architecture on a background of significant oedema. He was PN dependant with challenging management of his fluid balance. Due to a new acute renal injury with nephrotic range proteinuria, further stains on his colonic biopsies were requested. These stained positive with congo red, showing apple green birefringence which was suggestive of a diagnosis of Amyloidosis.
Following consultation with the National Amyloidosis Referral Centre, further investigations were requested which showed an amyloid load in the spleen (SAP scan) and chronic pelvic sepsis (PET CT) likely to be driving a chronic inflammatory state. Due to the advance nature of his disease, no active treatment could be offered and the patient unfortunately passed away 8 months into their hospital admission due to multi-organ failure.
Through reporting of this case, we want to raise awareness of Amyloidosis as a rare cause of Type 2 intestinal failure.

Introduction

Obscure gastrointestinal bleeding (OGIB) is defined as gastrointestinal bleeding of unknown origin that persists or recurs despite a negative finding from an initial bidirectional endoscopy. According to recent guidelines, capsule endoscopy was recommended first in overt OGIB, but it is unclear when it is appropriate to perform capsule endoscopy in overt OGIB patients.

Aims & Methods

We aimed to analyze clinical outcomes with regard to the timing of capsule endoscopy in overt OGIB patients. We conducted a single-center retrospective study enrolling patients who had undergone capsule endoscopy for overt OGIB between February 2010 to December 2021. We included hospitalized patients who underwent capsule endoscopy for overt OGIB after negative bidirectional endoscopy. We investigated the diagnostic yield of capsule endoscopy, rebleeding rate, length of hospital stay, initial hemoglobin, and the amount of blood transfusion with regard to the timing of capsule endoscopy.

Results

A total of 118 patients underwent capsule endoscopy to assess overt OGIB. The diagnostic yields in the groups that underwent capsule endoscopy < 48h and > 48h from the last overt OGIB were 50.0% and 22.0%, respectively (P=0.017). Rebleeding rate and the length of hospital stay were not significantly different between the two groups. Initial hemoglobin level in the group who underwent capsule endoscopy > 48h group was lower than in the < 48h group (8.8±3.0 vs. 10.7±3.7, P=0.015).

Conclusion

Performing capsule endoscopy within 48 hours from the last overt OGIB resulted in a higher diagnostic yield. Performing capsule endoscopy within 48 hours may improve the clinical outcomes of patients with overt OGIB.

Introduction

Dysbiosis of the microbiome is associated with inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of IBD. However, data are scarce and primarily limited to animal studies

Aims & Methods

We aimed to assess if stool microbiome characteristics are associated with disease severity, disease location, and inflammatory pathways using microbiome data obtained from the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus program of the Crohn’s & Colitis Foundation for 926 CD and 491 UC patients. Characterization of stool shotgun metagenomics was conducted with MetaPhlAn2 and HUMAnN2 to determine abundance of taxa and functional pathways, respectively. ANOVA and linear regression analyses were conducted to associate bacterial composition and functional potential with the selected clinical and exploratory measures. Mucosal inflammation was assessed with mucosal transcriptome data.

Results

Most of the samples came from Caucasians and females, and approximately 70% patients were in remission. 295 of 727 patients with CD had disease location data and 83% of these patients had ileal involvement (Table 1). We observed distinct microbial profiles between patients with active disease versus inactive disease in both CD and UC. Specifically, oral commensals belonging to Veillonella, Klebsiella, Rothia, and Megasphaera were more abundant in patients with active disease in both CD and UC, while 21 genera including butyrate producing species belonging to Anaerostipes, Ruthenibacterium, Faecalibacterium and Roseburia were more abundant in patients with inactive disease in both CD and UC. We also noted differences in relative abundances of bacterial taxa by disease activity separately within UC and CD. In UC, the fecal microbial signatures with active disease were enriched with Escherichia, Haemophilus, and Anaerococcus, while Lactococcus, Proteobacteria_unclassified, Parasutterella, and Gemella were more abundant in patients with inactive disease. In CD, 9 unique genera were more abundant in patients with active disease, and 24 unique genera were more abundant in patients with inactive disease, consistent with the fact that CD manifests in both isolated disease locations (ileum or colon) or a combination of locations (ileocolonic) and UC is limited to the colon and the rectum. Indeed, 32 out of the 33 genera specific to CD, but not UC, were found to be associated with altered enrichment in ileal or ileocolonic CD compared to colonic CD, when stratifying by disease location.

Table 1 Population characteristics including disease activity (CD and UC) and CD disease location

Conclusion

Differences in microbiota by disease location suggest separate location-specific pathologies. Location-specific interactions between host intestinal gene expressions and microbiota, suggest key immune-mediated molecular pathways and relevant bacteria in intestinal tissue, which may guide drug development and precision medicine in IBD.

Disclosure

Christopher Morehouse, Ben Sparklin, Bret Sellman, Antonio DiGiandomenico, Vancheswaran Gopalakrishnan, Bastian Angermann, Ulf Gehrmann, Jessica Neisen, Emon Khan and Junmei Cairns are all employees of AstraZeneca.

Introduction

We lack reliable biomarkers to identify patients with inflammatory bowel disease (IBD) at a greater risk of severe disease course. With emerging evidence that early step-down treatment in severe patients leads to better disease outcomes, alongside worries about overtreatment of mild patients, there is a clinical need to identify such biomarkers.

Aims & Methods

In this study, we explore genetic variants associated with severe disease course for ulcerative colitis (UC) in a nationwide cohort of 4491 patients from Denmark.
We genotyped 4491 patients with UC (4153 from Danish birth blood spot archive; 338 from NorDIBD regional cohort), linking them with registry data capturing medical interactions throughout patients’ lifetimes. Patients who required 2+ IBD-related hospitalizations, 2+ IBD-related major surgeries, 1 IBD-related hospitalization and 1 IBD-related major surgery or use of systemic corticosteroids (≥5000 mg) in the first 3 years of diagnosis were defined as severe. We conducted a genome-wide association study comparing severe patients (N=1203) to those with a less severe disease course (N=3288).

Results

The GWAS identified a signal within the HLA region, with the HLA-DRB1*01:03 allele driving the association (OR=3.30 [2.23-4.87], P=2.08×10^-9, UC carriage rate=2.8%). We did not observe an association with CD severity in a similarly ascertained cohort of 3688 individuals (P=0.79).
Remarkably, carriage of DRB1*01:03 was associated with a seven-fold increase of major surgery risk (OR=7.05 [4.55-10.91], P=2.31×10^-16) (Table 1). At the point of diagnosis, carriage of DRB1*01:03 was associated with higher CRP levels (β=2.68, P=1.70×10^-7), f-cal levels (β=1.92, P=4.42×10^-3) and a higher rate of hospitalization at diagnosis (OR=1.64, P=0.014), suggesting that the effect on severity is not limited to disease progression.

Conclusion

In this large-scale, unselected nationwide cohort study, we find that HLA-DRB1*01:03 is a biomarker of UC disease course that is associated with a more severe presentation at diagnosis, as well as higher subsequent risk of surgery and hospitalization. Demonstrating the association at a genome-wide significance level for the first time, this study revitalizes findings from smaller studies at the beginning of the genetic era which explicitly recruited severe patients and made estimating carriage effects difficult.
While HLA-DRB1*01:03 is a low-frequency allele, patients who carry it are at a much higher risk of severe UC. As the cost of typing a single HLA allele is low (under 50 EUR) and several pharmacogenetic variants are beginning to be tested at diagnosis, we argue that it is a valuable addition to the arsenal of personalized healthcare tools.