bluuebunny/crossref_metadata_2025 huggingface dataset:
A221 AZATHIOPRINE DOSING THRESHOLD IN ANTI-TNF COMBINATION THERAPY FOR MINIMIZING IMMUNOGENICITY AND OPTIMIZING TREATMENT EFFICACY FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE. A RETROSPECTIVE COHORT STUDY
Authors: Alajeel N , Choi J , Khanna R , Wilson A
Published: February 2024

Background

Reported rates of anti-drug antibody (ADA) formation to tumor necrosis factor-a antagonists (anti-TNF) range from 20-75%. One way to reduce the risk of ADA formation is to combine a second immune-suppressing agent such as azathioprine (AZA) with the anti-TNF agent, known as combination therapy. However, it is unknown if the risk of combination therapy, including the additive risk of AZA and anti-TNF side effects, could be reduced by exposing individuals with inflammatory bowel disease (IBD) to the lowest dose of azathioprine while still maintaining the beneficial effect of ADA prevention.

Aims

To identify the minimum dose of AZA needed to prevent ADA formation to anti-TNF agents in individuals with IBD receiving combination therapy. We also assessed the occurrence of adverse drug events, treatment loss of response, treatment discontinuation and the need for treatment dose escalation.

Methods

A retrospective cohort study is ongoing in adult participants with IBDreceiving either infliximab or adalimumab in combination with AZA. Patients are divided based on their AZA dosage (low dose group, AZA ampersand:003C2mg/kg/day versus standard dose group, AZA 2mg/kg/day). All participants will be followed for 1 year and observed for the occurrence of ADA formation, adverse drug events, treatment loss of response, treatment discontinuation and the need for treatment dose escalation.

Results

To date, 48 participants are currently included (low dose, n=29; standard dose, n=19). 42 are on Infliximab and 6 are on Adalimumab. The occurrence of ADA was 17.4% in the low dose group and 20% in the standard dose group (pampersand:003E0.99). More participants lost response to treatment and discontinued anti-TNF therapy in the standard dose group (n=7/19, 36.8%) versus the low-dose group (n=8/29, 27.6%, p=0.54). More participants in the low-dose group received anti-TNF dose escalation (n= 20/29,68.9%) compared to the standard dose group (n=6/19, 31.6%, p=0.017). Adverse events, to Anti-TNF was seen in (n=3/19, 15.7%) in the standard dose group, in comparison to (n=4/29, 13.79%, pampersand:003E0.99) in the low dose group. Adverse events to AZA were surprisingly higher in the low dose group (n=14/29, 48.3%) while in the standard dose, it was (n=5/19, 26.3%, p=0.14).

Conclusions

The preliminary result of the study suggests that there is no significant difference in anti-drug antibody formation between standard and low doses of azathioprine in combination with anti-TNF therapy, in addition, data showed significant lower rates of Anti-TNF discontinuation and loss of response to treatment in low Azathioprine dose group. Completion of the study will help further define if low-dose AZA can be used for ADA prevention in anti-TNF combination therapy without compromising important clinical outcomes.

Funding Agencies

None
A226 NEUTROPHIL-TO-LYMPHOCYTE RATIO AT DIAGNOSIS PREDICTS COLONOSCOPIC ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASES (PIBD)
Authors: Aziz B , Belaghi R , Huynh H , Jacobson K , Mack D , Deslandres C , Otley A , deBruyn J , El-Matary W , Crowley E , Sherlock M , Ahmed N , Griffiths A , Walters T , Wine E
Published: February 2024

Background

Neutrophil-to-lymphocyte ratio (NLR) has been recently identified as a potential biomarker for several autoimmune conditions. NLR predicts disease activity in adults with inflammatory bowel diseases (IBD) but had not been studied in pediatric IBD.

Aims

Investigate the link between NLR and baseline colonoscopic disease activity in UC and CD, the need for surgery or admission, and one-year therapy response in children.

Methods

Pediatric IBD patients were prospectively enrolled into the CIDsCaNN database [Canada-wide inception cohort for pediatric patients with IBD]. The cohort included patients diagnosed between 2003–2022 based on ileocolonoscopy, histopathology, and established diagnostic criteria. Patients were excluded if they had other conditions affecting NLR, such as neoplasms and autoimmune diseases. Endoscopic disease activity was assessed using the Mayo endoscopic score (MES; dichotomized as low (0, 1) or high activity (2, 3)) in UC and SES-CD score (as continuous variable) in CD. Logistic regression was used to test the link between predictors and binary outcomes. Simple linear regression was used to analyze the relationship between continuous variables.

Results

576 UC and 1076 CD patients ampersand:003C18 years old were included. In UC, baseline NLR was significantly associated with baseline MES in univariate and multivariable logistic regression (multivariable OR= 1.5, 95% CI= 1.1–1.99, p= 0.019; Table). Patients with high-activity MES have significantly higher neutrophils (p= 0.0003), but lymphocytes wasn't different between the two groups. In CD, NLR was significantly correlated with SES-CD score in univariate and multivariable simple linear regression (multivariable coefficient= 1.4, 95% CI= 0.7–2.2, pampersand:003C0.0001; Fig1). Additionally, NLR predicted biologic-free remission in the CD cohort only in univariate analysis. NLR did not predict other the need for admission or surgery either in UC or CD.

Conclusions

Pediatric IBD patients with higher baseline NLR had a higher endoscopic disease activity. This establishes the significance of NLR as a non-invasive biomarker to help direct clinical decision making. This association suggests a role for neutrophils, as innate immunity cells in the acute stage of inflammation.

Multivariable logistic regression of the relation between baseline labs in pediatric UC and Mayo endoscopic score

Scatter plot demonstrating the relationship between baseline NLR and baseline SES-CD score

Funding Agencies

C.H.I.L.D.
A228 RISANKIZUMAB - DRUG INDUCED LIVER INJURY; A CASE REPORT
Authors: Borahmah F , Salh B , Chahal D
Published: February 2024

Background

Risankizumab is a humanized monoclonal antibody to IL-23. It was initially used in the treatment of plaque psoriasis with recent approval to extend use to treat moderate to severe Crohn’s disease with evidence of endoscopic healing and clinical remission of disease. In the drugs safety manual, it has been reported to have transient liver enzyme elevation that is asymptomatic and not to a degree requiring drug discontinuation. No reported data on steatohepatitis. In this article we describe a 28 year old female, who had no evidence of liver disease in the past who underwent treatment with Risankizumab and within several months developed evidence of steatohepatitis with radiological evidence of significant hepatomegaly.

Aims

Case report details Drug induced liver injury to Risankizumab.

Methods

Case Report

Results

Drug induced liver injury with elevated liver enzyme levels and liver biopsy showing drug related liver changes likely in the setting of Risankizumab use.

Conclusions

Risankizumab is a newly approved drug in the setting of Crohn's disease, although described in the drug assessment report that it may cause transient hepatitis or eleveted liver enzymes in the setting of lower drug dose for Psoriasis use, the higher drug level used in the setting of Crohn's disease has not been formally evaluated and no previous known case reports of Drug induced Liver Injury to Risankizumab causing severe steatohepatitis

Funding Agencies

None
A230 SARCOPENIA IN PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE IN PAEDIATRICS AND CLINICAL IMPLICATIONS
Authors: Dahlwi G , Yodoshi T , Church P , Ricciuto A
Published: February 2024

Background

Sarcopenia is defined in paediatrics as a decrease in muscle mass for a given age. The coexistence of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is recognized to be a distinct entity with a distinct phenotype. However, to date, there is no study that has assessed the prevalence of sarcopenia and its clinical implications in paediatric PSC-IBD, compared to paediatric colitis.

Aims

We first aimed to determine whether sarcopenia is more prevalent in paediatric PSC-IBD than children with colitis without liver disease. Our secondary aim was to explore the prognostic implications of sarcopenia in paediatric PSC-IBD both for liver and IBD outcomes.

Methods

This was a single-center retrospective cohort study including paediatric IBD patients with and without PSC who underwent magnetic resonance enterography (MRE) for clinical care. Psoas muscle area (PMA) at the L4-5 intervertebral disc level was calculated. Sarcopenia was defined as PMA ampersand:003C 3rd percentile for age and sex. The association between PSC and sarcopenia was examined using logistic regression, adjusting for variables selected using change in estimate method. Survival analysis was used to examine the association between sarcopenia and IBD/liver outcomes.

Results

A total of 85 IBD patients were included – 31 PSC-IBD and 54 colitis controls. Both groups had male predominance. A higher proportion of children with PSC-IBD had pancolitis (Pampersand:003C0.001), and PSC-IBD patients had less severe clinical IBD disease activity than controls (P=0.003). Sarcopenia was present in 39% PSC-IBD and 18% colitis (odds ratio (OR) 2.7, 95%CI 1.02-7.53, P=0.044). Adjusting for endoscopic Mayo score and biologic therapy exposure prior to MRE, the adjusted OR for the association between PSC and sarcopenia was 4.22, 95%CI 1.32-13.44, P=0.015. Sarcopenic patients were younger than non-sarcopenic patients (mean 12.4(SD2.9) years versus 14.3(SD2.3) years, P=0.003), and also had lower weight and height (Pampersand:003C0.001, P=0.002, respectively). Sarcopenia was not a risk factor for escalation to biologics and/or surgery (hazards ratio (HR) 1.18, 95%CI 0.55-2.50, P=0.67) nor for progression to liver fibrosis and/or portal hypertension (HR 0.40, 95%CI 0.044-3.54, P=0.40).

Conclusions

Sarcopenia was 4 times more frequent in PSC-IBD compared to colitis controls in our cohort, after accounting for differences in IBD severity and biologic exposure. Sarcopenia may represent an additional feature that is distinct to PSC-IBD versus colitis without associated PSC.

Funding Agencies

None
A231 EFFECTIVENESS OF DUAL BIOLOGIC THERAPY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE: A MULTICENTRE CANADIAN STUDY
Authors: Diaz F , Belaghi R , Walters T , Chea E , Friedland D , Wine E , Deslandres C , Huynh H , deBruyn J , Mack D , Otley A , Ricciuto A , Benchimol E I , Carroll M W , Church P , Carman N , Shaikh A , Griffiths A , El-Matary W
Published: February 2024

Background

The effectiveness of combining biologics for pediatric inflammatory bowel disease (IBD) is under-investigated.

Aims

To evaluate the effectiveness of dual biologic therapy in children with IBD.

Methods

Children and adolescents ampersand:003C 17 years old with IBD enrolled in the Canadian Children IBD Network (CIDsCANN) who received any biologic therapy were included. Patients were classified as cases if they received two biologics simultaneously, and controls if they were switched from one biologic to another. All cases and controls who met inclusion criteria were analyzed.

Baseline demographic and disease-specific data were collected. The primary outcome was clinical activity indices at the end of the 1-year period following the start of dual biologic therapy or the switch to a different biologic.

The Wilcoxon signed rank test (for continuous variables) and the Fisher exact test (for nominal variables) were used to compare demographic data. A multivariable Cox proportional hazard model was used to infer about disease activity reduction between the two groups. p ampersand:003C 0.05 was used to determine statistical significance.

Results

Twenty-six cases and 194 controls fulfilled the inclusion criteria. Demographic and disease-specific data are summarized in Table 1.

The most common combination was ustekinumab with vedolizumab in 11 (42.3%) patients; while the most common first biologic in the control group was infliximab (104, 54.1%) and the second was ustekinumab (109, 56.2%). The most common indication for the biologic therapy addition or switch was unsatisfactory clinical response.

No differences between cases and controls in reductions of disease activity indices were seen at the end of the 1-year period (Figure 1).

Conclusions

In children with IBD, dual biologic therapy was not more effective than switching from one biologic to another. We are currently investigating the safety of this approach.

Baseline data

Proportion of patients with 10- and 20-point reduction in clinical activity indices at the end of the 1-year period

Funding Agencies

None
A232 TEMPORAL TRENDS IN RE-HOSPITALIZATION RATES AMONG PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN THE POST-BIOLOGIC ERA
Authors: Dziegielewski C , Pugliese M , Begum J , Benchimol E I , McCurdy J , Murthy S
Published: February 2024

Background

Hospitalization for severe inflammatory bowel disease (IBD) flares or complications are a major source of morbidity and healthcare expenditure.

Aims

To assess temporal trends in 30-day and 90-day re-hospitalization rates among persons with Crohn’s disease (CD) and ulcerative colitis (UC) in the post-biologic era.

Methods

We conducted a population-based study of all non-elective IBD-related hospitalizations among patients with CD and UC in Ontario, Canada between April 1, 2002 and March 31, 2020. We identified individuals, admissions, and variables of interest from Ontario population health administrative datasets housed at IC/ES. We performed multivariable logistic regression analysis to evaluate the association between time period of hospitalization (2002-2007 vs. 2002-2007 vs. 2007-2012 for CD; 2004-2008 vs. 2008-2012 vs. 2012-2016 vs. 2016-2020 for UC) and rates of 30-day and 90-day re-hospitalization, adjusting for patient age, sex, co-morbidities, residential setting, income quintile, hospital type of initial admission, and clustering of hospital admissions within patients. We excluded patients with elective admissions or length of stay ampersand:003C24 hours, and those without continuous valid Ontario health care registration during the 90-day period following hospital discharge.

Results

There were 18,625 hospitalizations among 14,868 patients with CD, and 10,830 hospitalizations among 9,264 patients with UC. The 30-day re-hospitalization rate was 8.5% for patients with CD and 9.7% for patients with UC, while the respective 90-day re-hospitalization rates were 15.0% and 13.8%. For CD, re-admission rates differed across the 3 time periods (pampersand:003C0.0001 for 30-day and p=0.012 for 90-day). For UC, re-hospitalization rates differed across the 4 time periods for 30-day re-hospitalization (p=0.048), but not 90-day (p=0.080). There was a higher relative odds of CD-related re-hospitalization in 2002-2007 as compared to 2012-2017 (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.16-1.50 for 30-day; aOR 1.14, 95% CI [1.03-1.26] for 90-day). For UC, there was a higher relative odds of re-hospitalization in 2012-2016 as compared to 2016-2020 (aOR 1.26, 95% CI [1.05-1.52] for 30-day; aOR 1.22, 95% CI [1.04-1.43] for 90-day).

Conclusions

Up to 15% of patients with IBD in Ontario are re-admitted to hospital within 90 days of hospital discharge. The risk of re-hospitalization may have decreased over time in the post-biologic era. Our findings could be explained by changing access to inpatient and/or outpatient resources, improvements to medical and/or surgical care, shifting patient behaviour with respect to healthcare resource utilization, or residual confounding. These results require validation in other jurisdictions.

Funding Agencies

None
A233 PHENOTYPE OF MUSCULOSKELETAL MANIFESTATIONS IN A CANADIAN INCEPTION COHORT OF PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Dzongowski E , Suthar N , Walters T , Griffiths A , El-Matary W , Benchimol E I , deBruyn J , Berard R , Crowley E
Published: February 2024

Background

Musculoskeletal (MSK) manifestations, including arthritis and arthralgia, are among the most common extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD), reported in 20-30% of adult patients [1]. However, there is a paucity of data regarding MSK EIMs in the pediatric IBD population. A recent systematic review [2] found only 13 studies with limited results, due to heterogenous study design and data reporting methods. As such, little is known regarding frequency of MSK EIMs, their phenotype, or factors associated with their development.

Aims

The purpose of this study was to determine the frequency of MSK EIMs in a contemporary cohort of Canadian pIBD patients and describe the phenotype of MSK EIMs in this population.

Methods

This was a prospective longitudinal cohort study with data from the inception cohort of CIDsCaNN (Canadian Children IBD Network) comprising patients aged 2-17 from 12 Canadian pediatric centres, from 2014 to 2021.

MSK EIM frequency was calculated for the cohort, and for subgroups by age, sex, and IBD type. MSK-EIM phenotype was described from case report forms with specific MSK features reported. Variables were compared with Pearson Chi-square or Fisher’s exact test. For patients without MSK EIM at IBD diagnosis, a Cox regression survival analysis was used for time to MSK development, with right censoring for patients who never reported MSK EIMs.

Results

1,330 pIBD patients were included, with 761 males (57.2%) and 569 females (42.8%). There were 824 CD (62.0%), 382 UC (28.7%), and 124 IBD-U patients (9.3%).

81 patients (6.1%) reported MSK EIMs, with 63 CD (7.6%), 10 UC (2.6%), and 8 IBD-U (6.4%). CD patients were more likely to have MSK EIMs (7.6% vs 3.6% UC/IBD-U, p=0.002). 47 patients (58.0%) had MSK EIMs at or before diagnosis while 34 had them ampersand:003E4 weeks after diagnosis. There was no difference in overall frequency between sex or age groups, or time to MSK EIM development by age or ethnicity. Females were more likely to develop MSK EIMs, with odds increasing by 4.68 for each year after diagnosis (p=0.047).

59 (74.7%) MSK patients were seen by a rheumatologist. Peripheral MSK disease was in 51 patients (63%), axial disease only in 37. Peripheral and axial MSK symptoms followed the course of bowel disease in 40.3% and 28.1% of patients respectively, which were not significantly different.

Conclusions

MSK EIMs affect 6.1% of a contemporary cohort of Canadian pIBD patients.This is less than reported in literature, likely due to physician-reported nature of our data. Our next step is to compare pIBD patients with MSK EIMs to a matched group without, for bowel disease-related outcomes and response to medications.

Funding Agencies

Cassie and Friends Care and Research Network (CREW) funding.
A234 DOES FECAL CALPROTECTIN CORRELATE WITH INFLAMMATION ON ULTRASOUND IN CROHN’S DISEASE STRICTURES?
Authors: Gulhati V , Rosentreter R E , Motamedi M , Macci A , Ingram R , Kaplan G G , Ma C , Seow C , Novak K , Panaccione R , Lu C
Published: February 2024

Background

Fibrostenotic Crohn’s Disease (CD) is a challenging phenotype particularly due to the absence of intestinal anti-fibrotic therapies. Differentiating between strictures that are predominantly fibrotic as opposed to inflammatory remains a diagnostic dilemma. The ability to make this differentiation is critical to inform decisions for therapeutic approach. Fecal calprotectin (FC) is a stool marker reflective of intestinal inflammation. Very few studies have evaluated the relationship of FC concentration in ileal CD strictures and parameters of inflammation on intestinal ultrasound (IUS). Strictures on imaging are defined as 1) increased bowel wall thickness (BWT), 2) narrowed luminal apposition, and 3) pre-stenotic dilation (PSD). BWT and hyperemia (color Doppler signal (CDS)) are the most sensitive markers for CD inflammation on IUS. It is predicted that FC will match CDS in ileal strictures, similar to non-stricture phenotypes.

Aims

We aim to correlate FC levels with IUS inflammation of ileal CD strictures.

Methods

We performed a retrospective cohort pilot study exploring the relationship between FC levels and IUS inflammatory parameters in ileal strictures. FC levels were obtained ≤ 60 days of index IUS in fibrostenotic ileal CD patients. Individuals who underwent medication changes or experienced a clinical flare during this period were excluded. Inflammation was measured as BWT and CDS using a modified Limberg (ML) score. Pearson correlation for continuous variables, Spearman rank correlation and a Kruskal-Wallis test for FC and Limberg scale were completed.

Results

A total of 25 fecal samples were obtained from 17 patients with ileal strictures (47% male, median age 59 years (range 18-76)) were assessed. Median FC concentrations was 204.9 ug/g, IQR: 250.4. Median ileal stricture BWT was 7.0 mm (range 3.0–10.0). 40% (10/25) had ML1 (short chains in bowel), 32% (8/25) ML2 (long chains in bowel), and 28% (7/25) ML3 (long chains and perienteric fat). There was no correlation between FC and BWT (r= .02, p = 0.92), nor FC with ML scores (r=0.20, p= 0.25). In those with ML1, median FC was 232.4, while those with ML2 or 3, had a FC of 155.6 and 469.7, respectively. FC values were significantly different between the ML scores, pampersand:003C0.0001.

Conclusions

FC levels were not correlated with inflammatory parameters as seen on IUS in ileal CD. This unexpected finding may be due to ML2 scores having lower FC than anticipated, and small sample size. Other imaging factors such as loss of wall stratification need to be taken into account, and are perhaps more reflective of inflammation than BWT and CDS. This study provides the initial data to assess accuracy of FC and hyperemia of ileal CD strictures on IUS compared to histologic measures of inflammation on resected specimens.

Funding Agencies

None
A235 INFLAMMATORY BOWEL DISEASE AND PREECLAMPSIA: A PHYSICIAN SURVEY
Authors: Hanna Y , Tandon P , Huang V
Published: February 2024

Background

Preeclampsia is a disorder of pregnancy recognized as the second cause of maternal mortality worldwide. The association between IBD and preeclampsia remains unclear, but the significant comorbid profile, and lack of treatment aside from urgent delivery, make primary prevention a priority.

Aspirin was shown to halve preeclampsia rates and is recommended for primary prevention for women at risk. Despite high-quality evidence supporting Aspirin use and its well tolerated side effect profile, studies in non-IBD patients have demonstrated a knowledge-to-practice gap.

Aims

While there are no studies reported in women with IBD, prescribing rates may be even lower in this population, given that it may be incorrectly perceived to increase the risk of an IBD flare. Understanding physician perceptions could allow for a targeted educational approach to increase patient and physician awareness of the indications for Aspirin prophylaxis and its safety profile.

Methods

This is a cross-sectional survey study assessing physician perceptions and Aspirin prescribing patterns for preeclampsia prevention conducted from Mount Sinai Hospital. Demographic information, information on perceptions of preeclampsia risk in pregnant women with IBD, and on the perceived clinical benefit and risk of Aspirin prescribing were collected.

Results

A total of 38 Canadian healthcare professionals (HCPs) (15 Gastroenterologists, 14 Obstetricians, 5 General Practitioners, 2 General Internists, 1 nurse practitioner, and 1 midwife) were surveyed. Most HCPs were practicing for over 10 years (71%). In total, 68% of HCPs were comfortable with pregnancy-specific management of IBD. Most HCPs correctly identified all comorbidities associated with a high risk of preeclampsia including a history of preeclampsia (95%), renal disease (87%), and autoimmune disease (68%). A total of 55% of HCPs believed that pregnant patients with IBD were at increased risk of placental related diseases, and 56% agreed that these patients were at increased risk of preeclampsia specifically. Thirty-five percent of HCPs believed that IBD in remission, in the absence of other risk factors, was an indication for Aspirin prophylaxis. More so, 45% believed that IBD, with poor disease control, was an indication.

Only 8% of HCPs believed that Aspirin, when used for preeclampsia prevention, was associated with an IBD flare. In patients whom Aspirin prophylaxis was indicated, 77% agreed with its use, even in patients in whom disease control was poor. Finally, 63% agreed that the Aspirin dose should be 162 mg daily, and more than half (58%) agreed that the prescriber should be the patient’s obstetrician.

Conclusions

Most HCPs agreed that IBD was a risk factor for preeclampsia and that Aspirin prophylaxis was effective and safe for primary prevention. High quality studies are needed to evaluate risk of preeclampsia in IBD, especially in patients with active disease.

Funding Agencies

CAG
A236 THE EFFECTIVENESS AND SAFETY OF DUAL ADVANCED THERAPIES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE-SERIES
Authors: Howarth N C , Wilson A , Boyd T , Rohekar S , Basharat P
Published: February 2024

Background

Patients with inflammatory bowel disease (IBD) refractory to medical therapy and patients with IBD and concurrent extra-intestinal manifestations (EIMs) pose a challenge within gastroenterology. The small number of approved agents for IBD limits therapeutic options for this population. Utilizing a combination of newer biologic therapies with favourable safety profiles may provide a safe and efficacious option for treating patients with refractory disease or patients with well-controlled IBD but uncontrolled EIMs.

Aims

The aim of our study was to assess the safety and efficacy of dual advanced therapies for patients with IBD.

Methods

Patients at London Health Sciences Centre and St. Joseph’s Healthcare Centre on dual advanced therapies for inflammatory bowel disease were retrospectively assessed for a minimum period of 12 months. Major bacterial infection, adverse events, endoscopic, histologic, and clinical remission of IBD, and remission of EIMs of IBD were assessed.

Results

Five patients with Crohn’s disease receiving dual advanced therapies were identified. Stricturing Crohn’s disease was the predominant phenotype in 80% of the patients. One patient had perianal fistulizing disease. Dual therapy was initiated for concurrent management of EIMs in 80% of patients (enteropathic arthritis in 2 patients, spondyloarthritis in 2 patients, rheumatoid arthritis in 1 patient) and for refractory IBD in one patient. The majority of patients were on a combination of a tumour-necrosis-factor inhibitor and vedolizumab. Other advanced therapies included JAK inhibitors and ustekinumab. The patients were predominantly female (80%) and age at diagnosis was ampersand:003C50 years old in 80% of patients. No adverse events or major bacterial infections were observed during dual therapy. At the end of follow-up, all 5 patients were in clinical remission of their IBD and 4 patients demonstrated endoscopic remission. Only 60% of patients had remission of their EIMs within the follow-up period.

Conclusions

Our findings suggest that dual advanced therapies are safe and may represent a long-term treatment option for complicated patients with IBD.

Funding Agencies

None
A237 ROTAVIRUS VACCINE SAFETY IN INFANTS EXPOSED TO BIOLOGICS IN UTERO IN AN INFLAMMATORY BOWEL DISEASE POPULATION: A PROSPECTIVE COHORT STUDY
Authors: Jeyakumar Y , Mohmand Z , O'Connor K , Piche-Renaud P , Morris S , Huang V
Published: February 2024

Background

Biologics, the mainstay of therapy in patients with moderate-to-severe inflammatory bowel disease (IBD), undergo placental transfer during the second trimester of pregnancy and may remain detectable in the blood of exposed infants for up to 12 months. Due to concerns regarding the risk of immunosuppression and adverse events following immunization with live attenuated vaccines in infants exposed to biologics in utero, current guidelines recommend avoiding live vaccines in the first 6 to 12 months of life.

Aims

This study investigates whether the live rotavirus vaccine can safely be administered in infants exposed to biologics in utero.

Methods

We conducted a single-centre prospective cohort study, which included infants exposed to biologics in utero and born to mothers with IBD between October 1, 2020 and June 30, 2022. Infants were included in the study if they were assessed by Paediatric specialists at the Special Immunization Clinic (SIC) at SickKids Hospital (Toronto, Ontario). Mothers were followed by Gastroenterologists at the Special Pregnancy IBD Clinic at Mount Sinai Hospital (Toronto, Ontario). Data were collected on biologic agent exposure history, infant immune function testing, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunization. Adverse events following immunization included fevers, vomiting, diarrhea, and/or intussusception within 42 days following immunization.

Results

22 infants were included in the study. Of the 22 infants, 5 (22.7%) were exposed to infliximab in utero, 10 (45.5%) were exposed to adalimumab, 3 (13.6%) were exposed to vedolizumab, and 3 (13.6%) were exposed to ustekinumab. Of the 22 infants, 18 (81.8%) were recommended to receive the rotavirus vaccine by the SIC. 1 (0.05%) was not recommended to receive the vaccine due to neutropenia and low CD54 count on lymphocyte testing. The recommendation given to 3 infants is unknown. Of the 18 infants who were recommended to receive the vaccine, 16 (88.9%) received the vaccine and had no adverse events following immunization. 1 (6%) infant did not receive the rotavirus vaccine despite it being recommended due to parental choice. The rotavirus vaccination status and response in 1 infant recommended to receive the vaccine, is unknown.

Conclusions

Administration of the rotavirus vaccine in biologic-exposed infants did not result in adverse events in our study cohort. Although guidelines currently advise against live vaccinations in infants exposed to biologics in utero, specialist assessment of infant immune function can help encourage safe live vaccination uptake.

Funding Agencies

None
A238 BEST APPROACH TO SURVEILLANCE COLONOSCOPY FOR COLORECTAL CANCER IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE
Authors: Khan R , Dhalwi G , Ricciuto A
Published: February 2024

Background

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease and it has been recognized as a risk factor for hepatobiliary and colorectal carcinoma (CRC). Inflammatory bowel disease (IBD) is associated with a 6-fold increased risk of CRC as compared to the general population but with co-existing PSC, this risk rises to 30-fold and hence CRC surveillance is critical in these patients.

Aims

We performed a systematic review of the literature on surveillance colonoscopy for CRC in patients with PSC-IBD, with the aim of identifying the most effective approach.

Methods

The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under ID 472215. The search was executed in the databases Medline, EMBASE, Cochrane, Web of science, Scopus and Google Scholar databases from 1947 to May 2023. Observational or randomized controlled studies were included if patients had PSC-IBD (paediatric or adult) undergoing surveillance colonoscopy. There was no restriction for language. We used a modified version of the Newcastle–Ottawa Quality Assessment Scale to assess the risk of bias. Neoplasia was defined as the presence of low-grade dysplasia, high grade dysplasia or colorectal carcinoma.

Results

Amongst 2900 studies identified, 7 studies met the inclusion criteria with a total number of 379 PSC-IBD patients and 1884 IBD patients (all adult). The median frequency of surveillance colonoscopy was every 0-2 years. The most common endoscopic presentation of dysplasia in PSC-IBD was a normal appearing mucosa or subtle abnormalities such as mild inflammation. Three studies performed random and targeted biopsies and only one study did quadruple random biopsy (every 10 cm of the colon). Two studies used chromoendoscopy and high-definition endoscopy whereas another two studies used white light colonoscopy. Studies varied in terms of the number of biopsies taken and timing for the frequency and initiation of surveillance. Outcomes included intensive surveillance, resection, and colectomy. Our meta-analysis of 2 studies that reported the prevalence of colorectal dysplasia in PSC-IBD patients revealed a pooled prevalence of 21% (95% CI 1.4%-28%, I2 = 0%, Pampersand:003C0.597, shown in Figure 1)

Conclusions

Colorectal dysplasia is prevalent in patients with PSC-IBD and is associated with worse disease outcomes. As a result, PSC-IBD patients should be screened annually from the diagnosis of PSC. However, there is variation in practice, and no clear consensus on the best approach to perform screening colonoscopy in this population. Literature comparing various approaches is very sparse. Additional high-quality studies on this subject are needed to guide practice, particularly in paediatrics where data are non-existent.

Figure 1: Forest plot for meta-analysis of CRC dysplasia prevalence in PSC-IBD

Funding Agencies

None
A239 MOTIVATIONS BEHIND CAM USE IN PATIENTS WITH CROHN'S DISEASE AND ULCERATIVE COLITIS
Authors: Klemm N K , Trasolini R , Bressler B , Rosenfeld G , Leung Y
Published: February 2024

Background

Complementary and alternative medicine (CAM) use is common in IBD patients and impacts compliance with conventional treatment. Gastroenterologists should understand the motivational factors of CAM use—factors that push patients away from standard therapy or pull towards CAM. Our study describes the motivations behind CAM use for IBD and evaluates differences between CD and UC patients.

Aims

To compare the motivations behind CAM use between CD and UC patients.

Methods

Retrospective cohort survey of patients over 18 years old with IBD, evaluated by gastroenterologists at a tertiary care referral centre from January 1 to December 31, 2019. Only patients that reported CAM use were included. Chi-square and independent t-tests were performed and p-value ampersand:003C0.05 was significant.

Results

Of the 230 completed surveys, 193 reported CAM use (CD:57.5% & UC:42.5%). Demographics, disease duration and hospitalizations were similar, but CD patients had lower SIBDQ scores (CD:48.1 & UC:53.5 pampersand:003C0.001).

Both groups were largely influenced by their social network to use CAM (CD:33% & UC:31.3%) and did not feel well informed of CAM (87.4%). CD and UC patients had similar push and pull factors. Push factors included lack of improvement (39%) and side effects (20%) with conventional treatment. Pull factors included the desire for a holistic approach (21%) and to improve mood (35%). Most patients hoped fatigue 62.7%, diarrhea 61.7% and abdominal pain 58.0% would improve with CAM.

Conclusions

Despite differences in QoL, push and pull motivations for CAM use do not differ between CD and UC patients. Most users do not feel well informed of CAM and ongoing dialogue is important for patient-centred care.

Table 1: Characteristics of CAM use

Funding Agencies

None
A240 THE PROTECTIVE EFFECT OF HYMENOLEPIS DIMINUTA INFECTION IN EXPERIMENTAL COLITIS CAN BE INDEPENDENT OF IL-4RΑ SIGNALING
Authors: Kraemer Rocha L , Li S , Rajeev S , Wang A , McKay D
Published: February 2024

Background

Helminth parasites are potent inducers of Th2 immunity, characterized by the production of IL-4, IL-5, IL-13 and IL-10, and mobilization of regulatory cells. This orchestrated immune response establishes an immunomodulatory and/or immunosuppressive environment that may be protective against colitis and other inflammatory diseases. Earlier studies reveal that infection with the tapeworm parasite Hymenolepis diminuta ameliorates chemical-induced colitis in immunocompetent mice, and highlighted participation of the anti-inflammatory cytokine IL-10 in the mechanisms of protection. Moreover, the IL-4ra/STAT6 signaling pathway plays a pivotal role in promoting the Th2 immune response that is crucial for parasite expulsion: IL-4ra KO mice cannot expel the worm. However, the need for activation of IL-4rasignaling in the suppression of colitis by H. diminuta infection is unknown.

Aims

To determine if the inhibition of DNBS-induced colitis evoked by infection with H. diminuta requires IL-4ra signaling.

Methods

IL-4ra KO mice (n=4-8/group) were orally infected with 5 viable cysticercoids of H. diminuta and 8 days post-infection (dpi) were treated with 2.5 mg of dinitrobenzene sulfonic acid (DNBS). Subsequently, mice were assessed 72h post-DNBS. Disease was assessed by macroscopic disease activity score, colon length, weight loss, MPO activity of the colon, and leucocyte profile by blood count. Production of IL-10 by concanavalin-A (con-A; 48h)-stimulated splenocytes was measured by ELISA.

Results

An increase in blood eosinophilia in H. diminuta infected mice indicated a successful infection. DNBS treatment induced acute colitis in IL-4ra KO mice, and surprisingly prior infection with H. diminuta resulted in significantly less severe colitis, as evidenced by reduction in macroscopic disease activity score, prevention of weight loss, reduced MPO colon levels and maintenance of regular colon length. However, splenocytes from H. diminuta-infected IL-4ra KO mice did not show increased IL-10 production evoked by con-A compared to cells from non-infected mice.

Conclusions

These results indicate that the protection against DNBS-induced colitis by prior infection with H. diminuta can occur in the absence of IL-4ra signalling. This suggests redundancy in the anti-colitic effect of infection with this helminth parasite, such that absence of IL4ra is compensated for via another, yet to be determined, mechanism. We speculate that this may be via participation of type 2 innate lymphoid cell activity, mobilization of regulatory T cells or innate immunity: all possibilities that need to be rigorously tested.

Funding Agencies

CIHRBeverly Phillips Rising Star and Cumming School of Medicine (U. Calgary) Fellowships
A243 BONE MINERAL DENSITY AND DIETARY BONE NUTRIENTS DIFFER IN PATIENTS WITH CROHN'S DISEASE STRICTURES
Authors: Macci A , Basit J , Klassen R , Rosentreter R E , Bindra K , Lethebe B , Boyd S , Billington E , Raman M , Burt L , Lu C
Published: February 2024

Background

Crohn’s disease (CD) phenotypes include inflammatory (non-stricture) and stricture behaviours. Strictures are bowel narrowing’s that may lead to obstructions and subsequent dietary restrictions to prevent blockages. Bone mineral density (BMD) in CD is affected by many factors including corticosteroid use, CD itself, but also dietary changes. Clinical gold standard for measuring BMD is by dual x-ray absorptiometry (DXA) scans. High-resolution peripheral quantitative computed tomography (HR-pQCT), a more precise imaging modality assesses volumetric BMD, bone geometry and bone microarchitecture. We aim to compare dietary intake, and bone quality in both stricture and non-stricture CD.

Aims

To identify nutritional patterns, bone quality differences and deficiencies between two subtypes of CD; including energy intake, dietary components and/or micronutrients

Methods

Individuals (≥55 years old) with ileal CD strictures (fixed, angulated bowel or thickened bowel with pre-stenotic dilation on diagnostic imaging), or inflammatory CD were prospectively recruited. Patients with short gut, celiac disease, dysphagia history were excluded. All patients completed DXA hip and spine scans and HR-pQCT radius and tibia scans. Dietary assessment questionnaires (Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24), and Diet History Questionnaire III for food frequency over the past year were completed.

Results

56 (27 inflammatory (48% female, mean age 64.2, BMI 28.7, 16 years CD duration) and 29 strictures (45% female, mean age 65.9, BMI 27.3, 25 years CD duration, 15 (51.7%) prior bowel resection) were included. 31/56 (55.4%) patients were on biologics and 11 (19.5%) had past corticosteroid exposure. DXA-based BMD for stricture versus non-stricture CD patients was not significantly different at the hip or spine. However, HR-pQCT-based radial total BMD (p=0.03), cortical thickness (p=0.01) and cortical area (p=0.04) were lower in stricture than non-stricture patients.11 (7 stricture, 4 inflammatory) patients with past steroids consumed more dairy (p=0.01), vitamin D (p = 0.04), and calcium (p=0.03) than other CD patients. Stricture patients had significantly less consumption of vitamin K (p=0.001), vegetables (p=0.02), calcium (p=0.03), and dairy (p=0.03).

Conclusions

Patients with CD strictures have lower BMD and cortical bone quality at the radius than those without strictures. Patients with CD strictures also consume significantly less vitamin K, calcium, and dairy, all vital dietary components to prevent OP, compared to non-stricture patients. Overall, the skeletal fracture risk is likely much greater in CD patients with strictures than without, due to greater inherent bone fragility, and less consumption of key nutrition building blocks of bones.

Funding Agencies

Koopmans Memorial Research Fund
A244 DEVELOPING AND ASSESSING THE EFFECTIVENESS OF A REMOTE MONITORING PROTOCOL FOR ULCERATIVE COLITIS PATIENTS - ULCERATIVE COLITIS CLINICAL OUTREACH (UCCO)
Authors: MacKay S A , Hagerman C , Parsons D , Dieleman L , Hoentjen F , Kroeker K , Peerani F , Wong K , Halloran B
Published: February 2024

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease which requires regular gastroenterologist monitoring. Outpatient monitoring programs to date have focused on clinical scores alone, leaving patients with asymptomatic inflammation susceptible to undertreatment despite increased risk of flares and colorectal cancer. The University of Alberta IBD Unit developed and piloted an outreach and remote monitoring protocol for UC patients including clinical and biochemical variables. We assessed the effectiveness of this protocol at improving UC care.

Aims

This study aimed to develop a clinical outreach and remote patient monitoring protocol for UC patients and assess the impact this protocol had on disease management.

Methods

Biologic naïve adult UC patients who had not been reviewed by their gastroenterologist in at least six months were contacted by phone and mailed monitoring kits with Partial Mayo, Sutherland Index, and medication adherence questionnaires and a requisition for blood work and fecal calprotectin (FCP). Results were compiled and sent to each patient’s gastroenterologist. Participating gastroenterologists completed a survey about the perceived utility of the protocol and intended UC management changes.

Results

85 patients completed the protocol. 86.4% of physician surveys rated the protocol as helpful to clinicians. UC management was changed in 55.6% of cases, with 82.2% of changes being management escalations. Six patients had active flares and 17 patients with asymptomatic inflammation were identified. Endoscopy was completed for 23 patients, with active disease observed in 78.2% of cases. Six patients started biologic therapies based on the protocol and endoscopic findings. UC management escalations were significantly predicted by FCP and Sutherland Index scores on logistic regression analysis.

Conclusions

This protocol had a meaningful impact on UC management and identified patients with active disease in both the presence and absence of clinical remission. Remote outpatient monitoring in UC should include collection of both FCP and clinical scores every six months to improve UC management.

Funding Agencies

None
A245 CROHN’S DISEASE-ASSOCIATED BACTERIAL PATHOBIONT EVOKED EPITHELIAL MITOCHONDRIAL DAMAGE DRIVES TYPE I INTERFERON EXPRESSION
Authors: Mohan A , Wang A , McKay D , Shutt T
Published: February 2024

Background

The Crohn’s disease-associated adherent invasive E. coli (AIEC) (strain LF82) decreases mitochondrial membrane potential and fragments the epithelial mitochondrial network. Due to the evolutionary history of mitochondria as former bacteria, they present a variety of molecular patterns known to trigger innate immune responses. Specifically, mitochondrial DNA (mtDNA) released following mitochondrial damage causes upregulation of type I interferons, priming inflammatory signalling. Thus, we hypothesized that AIEC-induced mitochondrial dysfunction results in mtDNA release to activate innate immune signalling that could contribute to disease pathogenesis in the gut.

Aims

We aimed determine if an inflammatory response occurs downstream of mitochondrial damage evoked by E. coli-LF82 infection.

Methods

Control T84 epithelial cells, T84s infected E. coli-LF82 (108 cfu, MOI=100, 4h) and T84s infected with the commensal E. coli-HB101 (108 cfu for an MOI=100, 4h) were collected for protein and RNA extraction. RNA was used to measure IFNα and IFNβ expression following infection, while protein was used to measure upstream mediators including phosphorylation of TANK Binding Kinase-1 (TBK1) via Western blot.

Results

Epithelia infected with E. coli-LF82 but not E. coli-HB101 displayed dramatic fragmentation of their mitochondria network and increased levels of phosphorylated-TBK1 compared to control T84 cells (pampersand:003C0.01). Assessment of IFNα and IFNβ mRNA revealed significant up-regulation E. coli-LF82 infected T84 cells and human colon organoids.

Conclusions

Our findings identify a novel role for E. coli-LF82 in activating type I interferon response and for the first time show AIEC-induced activation of TBK1 and type I interferons, which may occur through mitochondrial damage, rather than through response to bacterial molecular patterns. As a result, our findings suggest that the AIEC colonization seen in Crohn’s disease may dysregulate inflammatory signalling through mitochondrial damage. Ultimately, we believe this dysregulation of inflammatory signalling may sensitize the host to further inflammatory signalling, contributing to the pathogenesis of inflammatory bowel disease.

Funding Agencies

CIHR