bluuebunny/crossref_metadata_2025_split 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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