bluuebunny/crossref_metadata_2025 huggingface dataset:
A152 INTESTINAL INFLAMMATION DISRUPTS MICROBIAL ANTIGEN METABOLISM FACILITATING FOOD SENSITIZATION
Authors: Barbosa da Luz B , Rondeau L E , Muppidi P , Ling C , Dang R , Caminero A
Published: February 2025

Background

Patients with inflammatory bowel disease (IBD) report diverse food-related adverse reactions. Dairy is the most self-reported food intolerance in IBD. Emerging evidence suggests that altered diet-microbiota interactions can contribute to the development of IBD and adverse reaction to foods. We hypothesize that microbial alterations in IBD patients facilitate adverse reactions to foods.

Aims

To investigate the role of intestinal inflammation on microbial metabolism and food sensitization.

Methods

To investigate the effects of inflammation on microbial metabolism of food, eight-week-old C57BL6 mice were exposed to different concentrations (1.5 – 3.5%) of dextran sodium sulfate (DSS) for 5 days, then gavaged with dairy proteins. To study the role of inflammation in food sensitization, C57BL/6 mice were exposed to 3% DSS for 5 days, then sensitized to dairy proteins (6 mg casein/whey protein) using 4 oral administrations of cholera toxin (20 ug/mouse). After 1 week of recovery, sensitized mice were exposed to either a dairy-free or dairy containing diet for 7 days. Finally, the effects of inflammatory-mediated microbial alterations on food sensitivities were studied in gnotobiotic mice. Germ-free C57BL6 were colonized with DSS-inflamed microbiota or healthy SPF microbiota. After 3 weeks of colonization, the mice were sensitized to dairy proteins as described above, exposed to dairy and one cycle of DSS. Intestinal microbiota composition (16S sequencing) and function (digestion assays), and markers of intestinal inflammation (disease activity index, histological damage, cell infiltration and pro-inflammatory genes expression) were analyzed.

Results

DSS led to pronounced changes in the intestinal microbiota, impaired microbial capacity to degrade dairy proteins and increased systemic access of antigens. Inflammation also facilitated food sensitization characterized by immune cell infiltration (polymorphonuclear cells and CD3+) and mast cell proliferation in the colonic mucosa, and generation of systemic IgE and IgG levels. Dairy increased genes associated to immune cell recruitment and apoptosis in sensitized mice, and increased of apoptosis in the colon was confirmed by staining (TUNEL). Finally, mice colonized with microbiota from DSS-inflamed mice showed a worsening in inflammatory parameters during the dairy-diet intervention after sensitization. These results suggest that microbial alterations after inflammation facilitate the onset of food sensitivities and exacerbate food-mediated immune reactions in the colon.

Conclusions

Intestinal inflammation facilitates sensitization to foods by altering microbial antigen metabolism in the colon.

Funding Agencies

CCC
A154 TEMPORAL TRENDS OF DEPRESSION HOSPITALIZATION AND SUICIDE DEATH IN THOSE WITH INFLAMMATORY BOWEL DISEASE
Authors: Markovinovic A , Coward S , Ma C , Shaheen A , Kaplan G G
Published: February 2025

Background

Individuals with inflammatory bowel disease (IBD) are known to be more susceptible to mental health disorders such as depression. However, literature examining severe outcomes of depression in IBD, including hospitalizations due to depression and death by suicide, is limited.

Aims

To describe trends in depression hospitalizations and suicide deaths in individuals with IBD living in Alberta compared to matched controls.

Methods

This population-based study used a validated algorithm in administrative data to identify the prevalent IBD population and 10 to 1 age- and sex-matched controls in Alberta from fiscal year 2002/03 to 2021/22. The primary outcomes were hospitalization for depression and suicide death. Annual prevalence rates of depression hospitalization were calculated per 1,000 persons. Average annual percent change (AAPC) with 95% confidence intervals (CI) were calculated from Poisson or negative binomial models. Rates and AAPCs for depression hospitalization in IBD cases were stratified by age (<18, 18–40, 41–64, and ≥65), sex (male or female), and IBD type (Crohn’s disease or ulcerative colitis and inflammatory bowel disease unclassified [IBD-U]). Suicide deaths were reported as a proportion of the prevalent IBD population and as an AAPC (95% CI) calculated from a log-binomial model.

Results

Table 1 describes depression hospitalizations in the prevalent IBD population (n=42,903). Hospitalization rates for depression in those with IBD decreased with an AAPC of −4.25% (95% CI: −5.51, −2.96) from 4.42 per 1,000 in 2002/23 to 2.08 per 1,000 in 2021/22, while hospitalization rates for depression in controls decreased with an APPC of −2.37% (95% CI: −2.90, −1.94) (Table 1, Figure 1). Hospitalization rates for depression in those with IBD decreased for all stratifications except pediatric cases (AAPC: 2.03%; 95% CI: −5.99, 10.72) (Table 1). Suicide deaths occured in 0.23% (n=99) of the prevalent IBD population and remained stable over time (AAPC: −0.09%; 95% CI: −3.82, 3.79).

Conclusions

Despite the decreasing hospitalization rates for depression in individuals with IBD, suicide deaths have remained stable at 0.23%.

AAPCs and rates of depression hospitalization in those with IBD, stratified by age, sex, and IBD type

*denotes statistical significance

Temporal trends in depression hospitalization in IBD cases and matched controls

Funding Agencies

CIHR
A162 INTERLEUKIN-4 SIGNALING IS NOT A PREREQUISITE FOR HELMINTH-THERAPY PROTECTION AGAINST COLITIS
Authors: Kraemer L , McKay D , Wang A
Published: February 2025

Background

Infection with helminth parasites drives Th2 immunity, characterized by the cytokines IL-4, -5, -13, and IL-10, and expansion of regulatory cells. These orchestrated immune responses promote an immunomodulatory/immunosuppressive environment, which can protect the host from concomitant inflammation. Mice infected with the tapeworm Hymenolepis diminuta display a strong Th2 immune response and they are protected from DNBS-induced colitis. Surprisingly, preliminary data indicated that il-4ra-/- mice (where the worm establishes) were protected from DNBS-induced colitis. Here we sought to confirm or refute the findings in il-4ra-/- and, if positive, investigate the role of IL-10 and macrophages in the anti-colitic effect.

Aims

To determine if IL-10 and macrophages play key roles in the protection against colitis in il-4ra-/- mice infected with H. diminuta.

Methods

BALB/c (WT) and il-4ra-/- mice (IL-4ra-/-) (n=4-15/group) were orally infected with 5 cysticercoids of H. diminuta and 8 days post-infection (dpi) were treated with 2.5 mg of dinitrobenzene sulfonic acid (DNBS) to induce colitis. In some experiments, mice were treated 3 times i.p. with neutralizing anti-IL10 antibody (100 mg/mouse) or clodronate-liposomes (100 ml/mouse) to deplete macrophages (5 days and 24h before and after DNBS). Mice were necropsied 72h post-DNBS and disease was assessed through macroscopic disease activity score (DAS), colon length, weight loss, colonic MPO activity, blood leucocyte profile and histopathological score. Cytokine production by antigen-specific (H.d. antigen 200mg/mL; 48h) stimulated splenocytes was measured by ELISA.

Results

DNBS treatment induced colitis in WT and IL-4ra-/- and prior infection with H. diminuta was anti-colitic in both groups as shown by reduced DAS, weight loss, MPO activity, and histopathology. Compared to WT, il-4ra-/- mice had less blood eosinophilia, and il-5 and il-10 production by worm-antigen stimulated splenocytes, although il-10 production was increased compared to splenocytes from uninfected control mice. Immunoneutralization of il-10 and macrophage depletion abolished the protective effects of infection with H. diminuta, with the clondronate-treated mice displaying severe disease.

Conclusions

Despite harbouring a patient infection with H. diminuta, il-4ra-/- mice are protected from DNBS-induced colitis that is, at least in part dependent on IL-10 and likely a phenotype of regulatory macrophage. The data suggest redundancy in the anti-colitic effects of H. diminuta infection, such that absence of il-4ra is compensated for via other, yet to be determined, mechanisms.

Funding Agencies

CAG, CIHRTRIANGLE
A168 DIFFERENTIAL ASSOCIATION OF DIETARY FIBER INTAKE WITH METABOLOMIC AND PROTEOMIC SIGNATURES LINKED TO THE RISK OF CD
Authors: Kim J , McShane C , Xue M , Lee S , Leibovitzh H , Shao J , Khorasaniha R , Griffiths A , Armstrong H , Moayyedi P , Croitoru K , Turpin W
Published: February 2025

Background

Epidemiologic studies have shown that increased dietary fiber intake may be associated with a reduced risk of developing Crohn’s disease (CD). Our previous research identified specific patterns of serum proteomics and metabolomics associated with CD onset.

Aims

We aimed to understand how specific dietary fibers might be associated with risk biomarkers of CD in a high-risk population.

Methods

In the CCC-GEM Project, a nested case-control cohort was established involving healthy first-degree relatives (FDRs) of individuals with CD. This cohort was matched in a 1:4 ratio, comparing those who developed CD with those who remained healthy. The intake of five energy-adjusted dietary fibers, including inulin, fructooligosaccharides (FOS), β-glucan, pectin, and arabinoxylan, was assessed using a food frequency questionnaire completed at recruitment. Of the serum markers measured at recruitment, 63 metabolites (Metabolon®) and 25 proteins (Olink®), and C-reactive protein (Prometheus®) were associated with future CD risk; 34 metabolites and 15 proteins were associated with increased CD risk, while 29 metabolites and 10 proteins were protective against CD risk. To evaluate the association between dietary fibers and these serum markers, we used generalized estimating equations, considering a false discovery rate-adjusted p < 0.05 as significant.

Results

Among 215 healthy FDRs, 41 developed CD during a median follow-up of 9.4 years, while 173 remained healthy. We found that 14 metabolites and eight proteins previously associated with an increased risk of developing CD in future were negatively associated with the intake of at least one dietary fiber, whereas six metabolites and five proteins linked to a decreased risk of CD development were positively associated with dietary fibers. In particular, the intake of inulin, FOS, and β-glucan was negatively associated with the CD-associated markers TREM1, MMP9, HGF, and sphingomyelin species (p < 0.001), and positively associated with isocitrate (p < 0.001), previously linked to a reduced CD risk. Furthermore, the consumption of inulin, FOS, β-glucan, anarabinoxylan were negatively associated with C-reactive protein levels (p < 0.05).

Conclusions

Our findings suggest that select fermentable dietary fiber intake may be protective against the development of CD by influencing the abundance of specific proteins and metabolites associated with CD risk. Further research is needed to directly explore the mechanisms of specific fermentable dietary fibers on CD development.

Submitted on behalf of the Crohn’s and Colitis Canada GEM Project Research Consortium, list available at www.gemproject.ca.

Funding Agencies

CCC, CIHRHelmsley Charitable Trust
A171 IL-23 RECEPTOR VARIANT PREDICTS ANTI-TNFα INDUCED PARADOXICAL PSORIASIS IN INFLAMMATORY BOWEL DISEASE
Authors: Natt N , Gindi M , Wilson A
Published: February 2025

Background

Anti-tumor necrosis factor (TNF)-α therapy is frequently used to treat inflammatory bowel disease (IBD). Paradoxical psoriasis (PP) is a known adverse effect of this drug class resulting in disfiguring skin lesions that impact quality of life and lead to treatment discontinuation. To date, there are no tools to identify individuals who are susceptible to developing PP. Variation in the IL-23 receptor (IL23R) gene has been linked to psoriasis onset and may be implicated in PP.

Aims

To study the incidence and outcomes of PP in anti-TNFα treated IBD patients at an academic centre in London, Ontario and examine risk factors associated with PP including the IL23R variant (IL23R1142G>A).

Methods

We performed a retrospective study of adult IBD patients treated with anti-TNFα therapies at London Health Sciences Centre between 2012 and 2024. Patient charts were reviewed for clinical variables and disease outcomes from the time of anti-TNFα exposure to treatment discontinuation or last follow-up. Patients’ serum was retrospectively genotyped for the IL23R1142G>A variant.

Results

We identified 496 IBD patients with 570 unique anti-TNFα exposures between 2012 and 2024. 26 patients developed 29 cases of PP while the remaining 473 patients did not develop PP after exposure to 542 anti-TNFα therapies. There was an increased proportion of patients with PP who had a positive family and personal history of psoriasis, though the latter was not significant (Table 1). The IL23R variant was more common in patients who developed PP compared to those who did not (46.2% vs. 5.1%, OR 16.04, 95% CI 6.69-38.41, Figure 1). The average time to develop PP was 9.5 months, with 55% of patients receiving high-dose anti-TNFα drugs. Majority of patients had moderate-to-severe disease (72.4%) and required treatment cessation (69.0%). All participants had complete resolution of PP following interruption of anti-TNFα therapy.

Conclusions

IL-23R mutations may identify those at risk for anti-TNFα induced PP. Personal and family history of psoriasis may also predict those at higher risk and should be elicited on assessment.

Table 1 - Baseline Characteristics

Funding Agencies

None
A179 A CANADA-WIDE STUDY OF TRENDS IN HOSPITALIZATION RATES FOR INFLAMMATORY BOWEL DISEASE
Authors: Coward S , Benchimol E , Bernstein C N , Avina-Zubieta A , Bitton A , Hoentjen F , Kuenzig E , Lu N , Leal J , Ma C , Murthy S , Novak K , Nugent Z , Otley A , Panaccione R , Peña-Sánchez J , Singh H , Targownik L , Kaplan G G
Published: February 2025

Background

Hospitalizations among individuals with inflammatory bowel disease (IBD) place a strain on healthcare resources. The decline in hospitalization rates during the era of anti-TNF therapies remains debated in the literature.

Aims

To examine temporal trends in hospitalization rates among individuals with in IBD across Canada.

Methods

We used population-based administrative healthcare data (2002–2014) from seven Canadian provinces (AB, BC, MB, NS, QC, ON, SK) to identify hospitalizations in prevalent IBD cases. Hospitalizations were categorized as: 1. all-cause, any hospitalization of an IBD patient; 2. IBD-related, admission for IBD or symptoms/comorbidities associated with IBD (eg. venous thromboembolism). We calculated hospitalization rates per 100 IBD persons with 95% confidence intervals (CIs) using IBD prevalence data. Hospitalization rates were forecast from 2015–2025, with 95% prediction intervals (PIs), using auto regressive integrated moving average models on log transformed data. We calculated average annual percentage change (AAPC) using Poisson models with quadratic equations applied for non-linear trends. We stratified by IBD subtype (CD, UC), age (<18, 18–64, 65+), and sex (female, male). We calculated AAPCs for counts to assess the actual number of hospitalizations.

Results

From 2002–2014, hospitalizations rates decreased for both all-cause and IBD-related admissions for IBD patients, and across age, sex, and IBD type (Table 1). In 2025, we forecast hospitalization rates to be 15.82 (95%CI:14.17,17.66) per 100 for all-cause and 7.87 (95%CI:6.16,9.90) per 100 for IBD-related. Hospitalization rates are falling, but AAPCs for hospitalization counts significantly increased for all-cause (2.65%; 95%CI: 2.42,2.89) and IBD-related (1.52%; 95%CI: 1.29,1.76). The disparity between decreasing rates and increasing counts is due to the faster rise in the AAPC of IBD prevalence (denominator) compared to hospital counts (numerator).

Conclusions

During the anti-TNF era (2002–2014), hospitalization rates for IBD steadily declined across Canada and are projected to continue decreasing through 2025. Despite this decline, the actual number of hospitalizations is increasing, likely driven by the rising prevalence of IBD.

¥ Includes IBD-Unclassified *Non-linear

Funding Agencies

CIHR
A182 THE IMPACT OF DISEASE STATUS AFTER BIOLOGIC INDUCTION THERAPY ON LONG-TERM OUTCOMES IN PERSONS WITH CROHN’S DISEASE
Authors: Brar G S , Tandon P , Haque M , Butt N , Sanon M , Naessens D , Pone E , Targownik L
Published: February 2025

NOT PUBLISHED AT AUTHOR’S REQUEST

Please acknowledge all funding agencies listed below

Funding Agencies: Study Supported by funding from Janssen
A185 ERYTHEMA NODOSUM AS A MARKER FOR OBJECTIVE DISEASE ACTIVITY IN INFLAMMATORY BOWEL DISEASE: A SINGLE CENTER RETROSPECTIVE STUDY
Authors: Sasson S , Kalisky I , Rosenfeld G , Bressler B
Published: February 2025

Background

Erythema Nodosum (EN) is an inflammatory condition characterized by tender, erythematous nodules, typically found on the extensor surfaces of the extremities. EN is linked to both immune-mediated conditions, such as inflammatory bowel disease (IBD), Behçet’s syndrome, and sarcoidosis, as well as non-immune-mediated conditions. In patients with IBD, EN affects 3–10% of those with ulcerative colitis (UC) and 4–15% with Crohn’s disease (CD), particularly in patients with colonic involvement. While EN has been thought to be associated with disease activity, this conclusion has been primarily based on symptom assessment, and a definitive association with objective measures, such as inflammatory markers or endoscopic activity, has not yet been established.

Aims

To investigate the association of EN to objective inflammatory assessments among IBD patients.

Methods

Using the IBD Center of British Columbia database, patients with active EN were assessed. For each patient, disease activity based on symptoms was evaluated. Objective assessments, such as colonoscopy and imaging modalities such as CT, MR, or video capsule enterography, were included if they were performed within a three-month window of the EN presentation. Fecal calprotectin and C-reactive protein (CRP) were collected if obtained within four weeks of the EN presentation, using thresholds of 250 µg/g and 5 mg/L respectively.

Standard descriptive analyses were conducted to evaluate any association between both objective and subjective measures of disease activity and the presence of EN.

Results

The initial search identified 165 patients with a documented presentation of EN. The mean age at presentation of EN was 40 years. The majority of EN patients had Crohn’s disease (89, 76%), and were predominantly female (86, 74%). Among those, 116 patients had at least one objective assessment within the prespecified time with 71 patients (61%) having a colonoscopy as a sole method to identify disease activity, while CRP, imaging, and fecal calprotectin were used in 28 (24%), 10 (9%), and 7 (6%) of the cases, respectively.

In regards to disease activity, 68 (58%) patients had gastrointestinal symptoms at the time of EN presentation. However, out of 116 cases, a total of 93 (80%) had objective evidence of active disease.

Conclusions

In this analysis of IBD patients with active EN, objective evidence of intestinal disease activity was found in a significant majority (80%) of cases, despite only 58% of patients reporting gastrointestinal symptoms at the time of EN presentation. These findings suggest that EN may be closely associated with underlying intestinal inflammation even in the absence of overt clinical symptoms. This highlights the potential importance of pursuing objective assessments in patients who present with EN, even with no overt clinical symptoms.

Funding Agencies

None
A187 VANCOMYCIN CAN INDUCE AND MAINTAIN REMISSION OF REFRACTORY INFLAMMATORY BOWEL DISEASE IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS – A CASE SERIES
Authors: Cintosun A , Narula N
Published: February 2025

Background

The microbiome is suspected to play a role in the pathogenesis of inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). Meta-analyses have shown a positive response for antimicrobials in IBD, although the results are difficult to apply clinically given the wide variability in antimicrobial modality and treatment regimen as well as perceived reduced effectiveness compared to advanced therapies. Fewer antimicrobial studies have been performed in the PSC population. There is some evidence that vancomycin may represent a treatment option with concurrent IBD and PSC.

Aims

To determine the clinical and endoscopic effect of vancomycin for patients with refractory PSC-IBD.

Methods

Retrospective chart review.

Results

We identified 6 patients (4 male) with IBD and PSC who were started on vancomycin (Figure 1). Four had ulcerative colitis (UC) and 2 had Crohn’s disease. Three had pre-existing cirrhosis; 1 of these patients had undergone liver transplantation for PSC. All had failed multiple therapies for IBD with up to 4 advanced therapies failed. One patient had previously required surgery for UC.

Patients were started on induction vancomycin at 125 mg 4 times daily or BID (twice daily) for 8 weeks followed by maintenance therapy at 125 mg BID or daily.

The initial response to vancomycin therapy was demonstrated for all 6 patients at early follow-up ranging from 1 to 3 months. All had improvement of clinical symptoms with reduction in stool frequency and improvement in consistency. Some had bloody stools, nocturnal symptoms, and abdominal pain, which also improved.

One patient is awaiting post-vancomycin endoscopy. The remaining 5 started with moderate-to-severe inflammation and improved to mild or no inflammation on follow-up endoscopy 2 months to 2 years after starting vancomycin. Two patients had documented repeat endoscopy at a longer period of follow-up (4 and 6 years) and maintained remission.

The follow-up duration ranged from 2 months to 6 years. No adverse effects to vancomycin were reported. None of the 6 patients required steroids, addition of alternative therapy, admission, or surgery.

All patients were on concurrent therapy (vedolizumab, ustekinumab, or 5-ASA) either started prior to or at the same time as vancomycin. Three of these patients discontinued their ustekinumab at 6, 8, and 14 months respectively given treatment effectiveness and maintained remission on vancomycin alone.

Conclusions

In a subset of patients with PSC-IBD, vancomycin can induce clinical and mucosal remission for refractory IBD. We present two dosing regimens which produced rapid clinical improvement and those with longer follow-up sustained durable results. Prospective studies with larger sample sizes are needed.

Funding Agencies

None
A188 NATURAL HISTORY OF PERIANAL FISTULAS IN PATIENTS WITH ILEAL POUCH ANAL ANASTOMOSIS
Authors: Fujiyoshi M , McCurdy J
Published: February 2025

Background

The natural history of perianal fistulas (PAF) in patients with ileal pouch-anal anastomosis (IPAA) remains poorly understood. Perianal fistulas can significantly impact the quality of life and clinical outcomes in patients who have undergone IPAA. To date, there is limited data available on the long-term progression, treatment responses, and overall outcomes of PAF in this unique patient population.

Aims

The primary aim of this study is to report the clinical outcomes of PAF in patients with IPAA.

Methods

We performed a retrospective, observation cohort study between 2000 and 2024. We included adults (>17 years) with an IPAA who developed a perianal fistula and a minimum of 1 year follow-up after PAF diagnosis. PAF disease activity was categorized on an annual basis according to the following disease activity patterns: remission, minimally active, relapsing-remitting, and chronic persistent. We also determined medication utilization, medication effectiveness and major adverse fistula outcomes (MAFO): a composite of hospitalization, surgical drainage of PAF and fecal diversion.

Results

A total of 29 patients with an IPAA and PAF were identified: mean (SD) age 49.3 (13.2); 19 (65.5%) female, and 17 (63.0%) with complex fistulas radiologically at the time of diagnosis. After a mean (SD) follow-up of 9.7 years (7.4), 7 (25.0%) patients required fecal diversion, and 2 (7.1%) patients underwent pouch excision. Annual PAF disease patterns are reported in Figure 1. At the last date of follow-up, 26 (92.9%) patients achieved fistula remission. A total of 16 (55.2%) patients underwent treatment with an advanced therapy: 14 (87.5%) anti-TNF and 2 (12.5%) Risankizumab. After initiating a first advanced therapy, 10 (62.5%) patients achieved fistula remission at 12 months. Furthermore, 3 (18.8%) patients developed a MAFO after initiating their first advanced therapy: 3 (18.8%) underwent surgical drainage, 1 (6.3%) was hospitalized, and 1 (6.3%) underwent fecal diversion for PAF.

Conclusions

This study demonstrated that the majority of patients with PAF in the setting of IPAA achieved fistula remission clinically, particularly after treatment with advanced therapies. Despite the high remission rates, a substantial subset of patients still required fecal diversion and pouch excision.

Annual perianal fistula disease patterns

Funding Agencies

None
A189 IMPACT OF PHYSICAL ACTIVITY AND MEDICATIONS ON BODY COMPOSITION DYNAMICS IN PEDIATRIC IBD PATIENTS: A PROSPECTIVE STUDY
Authors: Djani L , Orius K , Neale N , Dehbidi Assadzadeh L , Tongue G , Huang F , Yang X , Bouthot J , Deslandres C , Jantchou P
Published: February 2025

Background

Although inflammatory bowel disease (IBD) severity is associated with decreased body mass index (BMI) in pediatric patients, many of them gain weight during follow-up. Physical activity levels (PAL) are associated with lower BMI dynamics while overweight/obesity worsen health outcomes in children. Few studies have explored BMI evolution and its related factors in this population.

Aims

To investigate BMI dynamics in children with IBD from diagnosis to last follow-up and assess the impact of PAL, disease phenotype/activity, and medication on BMI changes.

Methods

Pediatric IBD patients prospectively completed the Canadian Health Measure Survey quarterly for one year to assess PAL and were classified into three groups based on PAL (sedentary, moderately active or extremely/vigorously active). Clinical disease activity was classified using physician global assessment, PUCAI and sPCDAI. BMI was assessed at each visit.

Results

A total of 256 patients (56% male, median age 14y [IQR (interquartile range): 13-16]) were included. At diagnosis, 56% were normal weight, 38% underweight, 5% overweight, and 2% obese. By the first visit, 74% were normal weight, 4% underweight, 17% overweight, and 5% obese. The median time from diagnosis to the first study visit was 29 months [IQR: 7-44] during which patients gained a mean of 2.97 (95% CI: 2.64;3.31) BMI points.

The following factors were associated with BMI gain: disease duration (Pearson Coefficient Correlation [95% CI]:0.42 [0.31;0.51]), age at diagnosis (-0.13 [-0.25; -0.01]), BMI at diagnosis (-0.23 [-0.34; -0.11]), BMI z-scores at diagnosis (-0.32 [-0.42; -0.20]) and higher age at inclusion (0.20 [0.08;0.31]).

In a multivariate logistic regression, we found that being underweight compared to normal weight (adjusted odds ratio (aOR) =0.15 [0.06; 0.39]) and exposition to anti-TNFα (aOR = (3.89 [1.17; 12.97]) were independently associated to the risk for overweight/obesity during follow-up.

Conclusions

We observed a 15% increase in overweight/obesity prevalence and a 34% decrease in underweight prevalence in patients over the studied interval. BMI gain was significantly linked to exposure to anti-TNFa, warranting further investigations.

Table 1. Mean BMI Differences Between Diagnosis and First Study Visit

Funding Agencies

None
A192 CHANGING TRENDS IN ARTHRITIS PREVALENCE AMONG INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE: INSIGHTS FROM A POPULATION-BASED STUDY
Authors: Crowley E , Kuenzig E , Widdifiled J , Benchimol E I , Lam M , Jairath V , Rohekar S , Targownik L , Watson M , Berard R
Published: February 2025

Aims

The burden of arthritis among individuals with inflammatory bowel disease (IBD) is poorly understood. We describe changes over time in the annual prevalence of inflammatory arthritis (IA) and musculoskeletal (MSK)-related physician encounters among individuals with IBD.

Methods

We conducted a retrospective repeated cross-sectional study using Ontario population-based health administrative data. We used the Ontario Crohn’s and Colitis Cohort which comprises all IBD patients derived from health administrative data using validated age-specific case-identification algorithms. Individuals diagnosed with IBD between April 01, 2003, and March 31, 2020 (population denominator) were followed from their first IBD code (index date) until they died or were lost to follow-up (out-migrated/lost health care coverage), or until the end of available follow-up data (March 31, 2020). We identified the cumulative prevalence of inflammatory arthritis (≥1 hospitalization/ED encounter or ≥2 physician billing claims with IA-related diagnosis codes with ≥1 by a rheumatologist within 365 days). Separately we identified the annual number of individuals with ≥1 hospitalization/ED encounter/physician billing claim with any non-trauma related MSK-specific diagnosis codes. The annual age- and sex-standardized cumulative prevalence of both IA and MSK among individuals living with IBD each year were determined.

Results

Over the study period, the number of individuals living with IBD increased from 54,283 in 2003 to 108,857 in 2020; the number of children <18yrs increased from 1,547 to 2,667. Among all ages, the age/sex standardized cumulative IA prevalence within the IBD cohort increased from 6.8% (95% CI 6.5-7.2%) in 2003 to 15.2% (95%CI 15.0-15.8%) by 2020 (Figure 1). IA was slightly more common among those with Crohn’s than ulcerative colitis (17.4% vs 13.2%, respectively). By 2020, IA prevalence was 6.8% among children/youth <18yrs, 17.4% among those 18-64yrs, and 23.1% among those ≥65yrs. Overall, crude annual prevalence of an MSK-related encounter remained relatively stable from 30.6% in 2003 to 27.7% in 2020.

Conclusions

This study is the first to provide population-level estimates of IA and MSK-related conditions in people with IBD. The cumulative prevalence of IA among individuals with IBD has steadily increased over time, particularly among those ≥65years, while MSK-related encounters have not. This may be related to increased physician recognition of IA or increased access to care and diagnosis. These findings have implications for healthcare costs and utilization, given the specialized care and expertise required to manage IA in the context of complex, comorbid conditions like IBD.

Funding Agencies

CCC
A194 PATTERNS OF INFLAMMATORY BOWEL DISEASES IN NORTHWESTERN ONTARIO
Authors: Lee C , Farahvash A , Smith S , Clark M , Zezos A , Siddiqui R , Dubois S , Rumbolt C , Green J , Zezos P
Published: February 2025

Background

Geographic disparity adds to the challenges of caring for patients with inflammatory bowel disease (IBD) in Canada. Northwestern Ontario is one of the least densely populated regions among Canadian provinces, with limited existing research examining patients affected by IBD.

Aims

We sought to 1) describe the clinical trends and characteristics of patients with IBD in Northwestern Ontario and 2) compare the course of disease among patients residing in urban versus rural areas.

Methods

Thunder Bay is the major site for specialized care in Northwestern Ontario, allowing for the inclusion of approximately all IBD patients in the region. This retrospective study involved data collected over a 25-year period from January 1, 1999 to October 1, 2024. Northwestern Ontarians with diagnostic confirmation of IBD were included. Deceased patients were excluded. Participants were identified using billing codes and keywords from electronic records of three gastroenterologists practicing at the Thunder Bay Regional Health Sciences Centre, the only tertiary care centre in Northwestern Ontario. Data were collected from clinic and hospital records. Student’s t-test and chi-squared test were used in statistical analysis.

Results

Among 2115 patients who were screened, this preliminary analysis identified 1061 IBD patients, including 546 (51.5%) with ulcerative colitis, 481 (45.3%) with Crohn’s disease, and 34 (3.2%) with unclassified colitis. Mean age was 52.6±17.3 years and 49.9% were female. Mean age at diagnosis was 36.2±17.0 years and median time to diagnosis was 5 months. There were significantly more smokers among patients with Crohn’s. Based on the last clinical encounter, 692 (65.2%) patients were in clinical remission, 174 (16.4%) were in active disease, and 186 (17.5%) were lost to follow up. Current medications included biologics (369, 34.8%), 5-ASA (366, 34.5%), immunomodulators (119, 11.2%), and glucocorticoids (71, 6.7%). Throughout the course of disease, mean number of Emergency Department visits and hospital admissions were 2.6±4.7 and 1.2±2.4 respectively, and 325 (30.6%) patients underwent IBD-related surgery.

The cohort included 752 (70.9%) urban residents and 309 (29.1%) rural residents. No significant difference was observed between urban and rural residents, including age, sex, disease type, prevalence of biologic use, disease severity based on the Montreal classification, or current disease status.

Conclusions

This study characterizes the patient population and clinical trends of IBD in a low population density region in Ontario. There appears to be homogeneity between rural and urban residents, with comparable patient and disease features, and access to medications including biologics.

Funding Agencies

None
A200 A POPULATION-BASED ASSESSMENT OF PHYSICAL ACTIVITY AND EXERCISE IN PERSONS WITH IBD
Authors: Dolovich C L , Chochinov S , Ly G , Oketola A , Narvey S , Larance S , Raman M , Webber S , Bernstein C N
Published: February 2025

Background

It is known that physical activity (PA)/exercise is associated with a reduced risk in chronic disease. However, less is known about its impact on inflammatory bowel disease (IBD) specifically. Research generally uses the terms ‘PA’ and ‘exercise’ interchangeably, which although similar, are overlapping classifications of activity. As a result, interpreting and comparing existing findings can be challenging.

Aims

We aimed to assess the physical activity and exercise profiles of persons with IBD, their limitations in undertaking PA/exercise, and how PA correlates with active disease and fatigue in a population-based sample in Manitoba, Canada.

Methods

A cross-sectional survey study was undertaken by participants in the University of Manitoba IBD Research Registry. The survey included sociodemographic factors, PA/exercise, the International Physical Activity Questionnaire (IPAQ), Inflammatory Bowel Disease Symptom Inventory (IBDSI), and Modified Fatigue Impact Scale (MFIS). Bivariate and logistic regression analyses were used to assess the association between PA and disease activity and fatigue.

Results

The survey was completed by 1257 of 2740 invitees (45.8%). The mean age of participants was 60.8 +/- 13.0 years. The most common type of PA and exercise that respondents participated in were walking for leisure/exercise (84%) and the most common type of PA and exercise avoided was running/jogging (16%). Physically active status per IPAQ was categorized as inactive-low in 42.5%, moderately active in 32.0%, and highly active in 25.5%. Average fatigue levels were mean 24.9 SD 18.9 per MFIS. PA and fatigue levels were similar for those >55 vs those <55 years. For ulcerative colitis (UC) persons, after adjusting for demographic and clinical factors, the odds of lower levels of PA were greater among females [aOR 95% CI, 1.76 (1.12-2.78)], ever smoked [aOR 95% CI, 2.55 (1.11-5.73)], active disease (per IBDS) [aOR 95% CI, 1.68 (1.07-2.62)], and with an increase in MFIS total score [aOR 95% CI, 1.02 (1.01-1.04)].

Conclusions

There was a high rate of inactive to low PA among persons with IBD. Females with UC especially need to be encouraged to increase their PA. While it is not surprising that persons with active disease may have reduced or even avoided PA, this requires further study. Since as a result, PA may reduce deconditioning that may accompany periods of active disease and increased fatigue. These findings underscore the need for tailored PA/exercise guidelines for individuals with IBD. Future research should explore objective measures of PA to better understand PA/exercise in both younger and older adult populations.

Funding Agencies

CAG, None
A201 USTEKINUMAB VERSUS VEDOLIZUMAB PREDICTORS OF RESPONSE IN IBD PATIENTS WITH ANTI-TNF EXPOSURE: A PRELIMINARY REPORT
Authors: Homsi H , Khan U , Lawendy B , Abbas U , Khanna R , Wilson A
Published: February 2025

Background

Ustekinumab and vedolizumab are biologics that are effective in treating inflammatory bowel disease (IBD). Previous studies using propensity score matching have found no significant difference in their efficacy overall. Interestingly, these studies did not highlight clinical variables associated with optimal drug response and other treatment outcomes which could help inform treatment selection for patients after anti-tumor necrosis factor (anti-TNF) agent exposure.

Aims

To evaluate clinical variables associated with response to ustekinumab versus vedolizumab in IBD patients with anti-TNF exposure.

Methods

A single-center retrospective cohort study was conducted in IBD patients with prior anti-TNF exposure, treated with one of ustekinumab or vedolizumab. Participants were assessed for clinical remission at 12 months using the Harvey Bradshaw Index for Crohn’s Disease (CD) (HBI≤4) and the Partial Mayo Score for Ulcerative Colitis (UC) (≤2). Secondary outcomes included 6-month remission, surgery, hospitalization, use of rescue glucocorticoids, adverse events, and treatment discontinuation in patients followed for at least 1 year. Potential clinical variables associated with the primary and secondary outcomes were assessed using multivariable logistic regression analyses for each drug group.

Results

A total of 118 patients (CD, n=61; UC, n=57) treated at a tertiary care center in London, Ontario, Canada, were included in the analysis. Patients received at least one dose of ustekinumab (n=58) or vedolizumab (n=60). For both the vedolizumab-exposed and ustekinumab-exposed cohorts, 6- and 12-month disease remission were associated with high dose therapy (vedolizumab, 12-month, adjusted OR=6.62, 95%CI 1.95-26, p=0.004; 6-month, adjusted OR=4.77, 95%CI 1.43-17.58, p=0.014 versus ustekinumab, 12-month, adjusted OR=4.08, 95%CI 1.19-15.26, p=0.029; 6-month, adjusted OR=4.57, 95%CI 1.30-18.34, p=0.022). For the vedolizumab-exposed cohort, treatment discontinuation was associated with age (p=0.039), weight (p=0.031) and high dose therapy (p=0.008). Similarly, the need for rescue glucocorticoids was associated with age (p=0.021). No other clinical variables were associated with the primary or secondary outcomes for either cohort.

Conclusions

Ustekinumab and vedolizumab demonstrated similar efficacy in achieving clinical remission in our study population. The odds of achieving remission from either at 6 and 12 months was higher amongst individuals receiving high-dose therapy. Vedolizumab treatment discontinuation was associated with a younger age and lower weight. No other clinical variables were associated with drug response in either cohort. Larger studies are warranted to confirm these findings and identify other predictors of response that can guide biologic selection in IBD management.

Funding Agencies

None
A208 MENTAL HEALTH, WORK IMPAIRMENT, AND MEDICATION SATISFACTION AMONGST INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE RECEIVING LONG-TERM BIOLOGIC AND ADVANCED TREATMENT
Authors: Hazan E , Stefanova E , Afshar A , Patel A , Targownik L
Published: February 2025

Background

Biologic and advanced immunotherapies have been shown to be effective in controlling biochemical, endoscopic, and histologic disease activity in individuals with Inflammatory Bowel Disease (IBD). However, there is limited data assessing the prevalence of somatic symptoms, mental health, and quality of life (QoL) in this population. To provide holistic care and appropriately manage both gut and somatic symptoms, it is critical to assess the prevalence of these symptoms and impairments.

Aims

This study assessed the prevalence of mental health deficits, quality of life, and work impairment in IBD patients who are being treated with biologic and advanced therapies for at least six months. The objective was to assess whether significant gaps in these domains persist as well as whether individuals are satisfied with their current advanced treatment.

Methods

Cross-sectional data was prospectively collected using a survey completed by individuals >18 years old, with a known diagnosis of Ulcerative Colitis, Crohn’s Disease, or Indeterminate Colitis, who have been receiving a biologic or advanced immunotherapy at a stable dose for >= 6 months. In addition to demographic data, the survey contained validated questionnaires assessing mental health, work impairment, and QoL. The presence of deficits in these domains was then evaluated using absolute scores and validated cutoffs.

Results

This study included 37 individuals who completed the survey as well as an additional 3 who completed part of it. 85% of respondents agreed that their current therapy has improved their symptoms and 62.5% of respondents are satisfied with their current treatment. 5.4-29.7% and 13.5-29.7% endorsed symptoms consistent with depression and anxiety respectively on different questionnaires. 51.4% of respondents endorsed active symptoms, and 56.8% endorsed symptom severity consistent with non-remission. A mean of 2.74 hours of weekly work productivity were lost due to IBD activity.

Conclusions

The majority of individuals with IBD on long-term advanced therapy report symptom improvement and satisfaction with their treatment. However, more than half endorsed ongoing symptoms of IBD, including work impairment, and nearly one-third endorsed mental health impairment consistent with depression or anxiety. This suggests that despite perceived treatment efficacy, significant gaps in these domains persist.

Funding Agencies

None
A209 EVALUATION OF THE ROLE OF DUSP1 AND DUSP16 GENES IN THE REGULATION OF INTESTINAL EPITHELIAL FONCTIONS
Authors: Huard R , Ntunzwenimana J C , Lévesque C , Rivard M , Goyette P , Rioux J D
Published: February 2025

Background

Inflammatory bowel disease (IBD) is associated with inflammation of the gastrointestinal tract, resulting from a dysregulation of the immune response to microbes in the intestinal lumen. Dr. Rioux’s laboratory has identified over 200 genomic regions associated with IBD. However, the challenge lies in identifying the causal gene in many of these. To address this problem, our laboratory completed a transcriptomic screen following overexpression of IBD-associated genes in intestinal epithelial cells. This study demonstrates that DUSP1 and DUSP16, two phosphatases targeting MAP Kinases (MAPKs), regulate the expression of several shared genes involved in intestinal differentiation and homeostasis.

Aims

Our research hypothesis is that the DUSP1 and DUSP16 genes participate in the regulation of biological processes involved in IBD and critical for the integrity of the intestinal barrier. More specifically, we want to determine how a reduction in DUSP1 and DUSP16 affects the biological pathways leading to the regulation of epithelial junction integrity, as well as inflammasome activation and IL-18 secretion.

Methods

In this project, we studied Caco-2 cells expressing DUSP1 or DUSP16 knockdown and their effect on intestinal epithelial cell functions. Among other things, we observed the cells’ ability to form a tight monolayer in 2D and spheroids in 3D. We also analyzed by Western blotting the impact of knockdowns on inflammasome formation and normal activity.

Results

Our results show that Dusp1 and DUSP16 knockdowns disrupt the ability of Caco-2 cells to form a tight monolayer and to form spheroids. In addition, our inflammasome analysis shows that KDs deregulate inflammasome activity.

Conclusions

These results demonstrate that decreased expression of the DUSP1 and DUSP16 genes impacts several functions essential to the maintenance of intestinal epithelial cell homeostasis, such as intestinal barrier integrity and inflammasome activation.

Funding Agencies

CIHRNIH
A210 BARRIERS TO ACCESSING INTERVENTIONS FOR PSYCHOLOGICAL DISTRESS IN PERSONS LIVING WITH IBD
Authors: Willett N , Heisler C , Rohatinsky N , Farina S , Stewart M , Vallis M , Shepherd T , Huard T , Neil E , Jones J
Published: February 2025

Background

Inflammatory Bowel Disease-related psychological distress (IBD-PD) refers to the emotional impact of IBD and is associated with mental health disorders, increased IBD activity, and premature mortality. Up to 90% of IBD patients experience some form of IBD-PD. The inability to provide person-centered care for IBD-PD that is proportional to clinical need is a critical issue.

Aims

The aim of this research initiative was to identify barriers to accessing evidence-based interventions for mental health support for IBD-PD.

Methods

This was a qualitative research study in which virtual semi-structured interviews took place between Oct 2021 and Mar 2022. The semi-structured interview script was developed with researchers, IBD care providers, and patient research partners and was guided by the COM-B Behaviour Change Wheel framework and the Theoretical Domains Framework (TDF). Adults (> 18 years of age) with a confirmed diagnosis of IBD were recruited from IBD clinics. Using thematic analysis as per Braun and Clarke (2006), codes were generated to identify themes.

Results

The total number of participants recruited was 14. The mean participant age was 37.6 years (range 23-57) with 57.1% as female (8/14). In terms of geographical locale, 28.6% lived rurally (4/14) and 71.4% (10/14) lived in an urban area. Thematic analyses identified the following themes: 1) Mental health is an important part of integrated IBD care. 2) Barriers to accessing psychological supports persist and include stigma, ignorance of IBD and mental health, costs and insurance coverage, and limited access and availability; 3) Health care providers should do more to address and refer patients to mental health supports.

Conclusions

From the perspective of the patient, accessing care for IBD-PD is challenging due to financial, physical, administrative, sociocultural, and informational barriers. Patients’ previous interactions with the healthcare system and mental health care providers color their view on mental health care and influence their preferences for context, setting and delivery mode for interventions. It is important to engage patients in the design and implementation of health service interventions. The information they share highlights barriers patients frequently encounter, and which aspects of care can be improved to meet patient-specific needs and match patient preferences.

Funding Agencies

None