P1226 Inflammatory Bowel Diseases and Prior Malignant Diagnoses - A Danish Nationwide Cohort Study 1996-2022

BACKGROUND Diverticulitis is a frequent and often serious condition of the colon, with its complexity increasing in the presence of inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC). This study aims to evaluate the impact of IBD on diverticulitis outcomes, focusing on hospitalization rates, surgical interventions, and mortality. METHODS We conducted a retrospective analysis of deidentified, aggregate patient data from the TriNetX research network. We used 122,511 diverticulitis patients, identifying those with concurrent CD or UC. Propensity score matching was employed to ensure balanced baseline characteristics between IBD and non-IBD patients, adjusting for variables such as age, gender, comorbidities (e.g., diabetes, chronic kidney disease), and lifestyle factors (e.g., tobacco and alcohol use). Hospitalization rates were calculated based on admissions directly linked to diverticulitis, as tracked in the dataset without distinguishing specific complications. Colectomy rates (both elective and emergency surgeries) and mortality were also assessed. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate time-to-event outcomes, including overall survival. RESULTS Out of the 122,511 patients, 1.4% had UC and 1.1% had CD. Compared to non-IBD patients, who had a hospitalization incidence of 9.2%, IBD patients had a substantially higher rate of 15.4% for UC patients and 12.1% for CD patients (p< 0.001). Additionally, IBD patients had higher rates of colectomy (UC: 3.8%, CD: 4.5%) than non-IBD patients (1.7%; p< 0.001). IBD patients had a significantly higher mortality rate than non-IBD patients, with 5.7% of UC patients and 4.9% of CD patients dying from their illness (p< 0.001). According to Kaplan-Meier analysis, IBD patients had a considerably decreased survival rate (p< 0.001), whereas UC patients had the lowest survival results. CONCLUSION Compared to individuals without IBD, those who have diverticulitis with concomitant IBD—especially UC and CD—had far worse clinical outcomes, including greater rates of hospitalization, colectomy, and death. These findings imply that customized care strategies may be necessary to improve outcomes for diverticulitis in IBD patients, highlighting the need for more monitoring and perhaps more aggressive treatment regimens. This table summarizes baseline characteristics of patients diagnosed with diverticulitis, highlighting differences among those with Crohn’s disease, ulcerative colitis, and non-IBD patients. This forest plot presents hospitalization, colectomy, and mortality rates among patients with inflammatory bowel disease (IBD) with concomitant diverticulitis.

Background Patients with Crohn’s disease (CD) and ulcerative colitis (UC) are at increased risk of developing intestinal cancer compared with the background population. However, less is known about the risk of extra-intestinal cancers (EICs). A previous meta-analysis did not find an increased overall risk of EICs but was limited by the scarcity of available studies and the short length of follow-up in those cohorts. The aim of this study was to conduct a systematic review and meta-analysis of population-based cohorts assessing the risk of EICs in inflammatory bowel disease (IBD) patients. Methods A systematic literature search was carried out. Only population-based studies reporting on the prevalence or incidence of EICs were included. All studies were screened (603), and included studies were quality assessed by two investigators (BL, MZ). Studies eligible for meta-analysis were pooled for events, expected events or events in a control-population, and the length of follow-up in patient-years. A meta-analysis of the overall and site-specific risk of EICs and a stratified analysis of the cohorts (according to whether there were most patients followed before or after the year 2000) were conducted. Results In total, 36 studies were included in the systematic review and 14 studies were included in the meta-analysis. The majority of the studies reporting on the overall risk of EICs in their respective cohort were inconclusive due to lack of power. In the meta-analysis, the overall risk of EICs was found to be increased in both CD (IRR: 1.45 [1.26, 1.67]) and UC (IRR: 1.15 [1.02, 1.31]) patients (Figures 1 and 2). The stratified analysis showed a significant increased risk of EICs among CD patients both before (IRR: 1.58 [1.09, 2.28]) and after (IRR: 1.47 [1.28, 1.69]) the year 2000, while no increased risk was found among UC patients. Assessing site-specific EICs, both CD and UC patients demonstrated an increased risk of skin and hepatobiliary malignancies. Furthermore, CD demonstrated an increased risk of haematological and lung malignancies (Figures 3 and 4). Conclusion In conclusion, this systematic review and meta-analysis demonstrated that IBD patients, both CD and UC patients, are at an increased risk of developing EICs; both overall and at specific sites. The transition of the millennium did not increase the risk of EICs in CD or UC patients. However, more studies with longer follow-up are needed to assess the true risk of EICs posed by IBD.

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

INTRODUCTION: Peripheral blood eosinophilia (PBE) has been recognized as a biomarker, identifying a subgroup of inflammatory bowel disease (IBD) patients with worse clinical outcomes. With more severe disease, anti-TNF therapy is often employed, with varied rates of success. The aim of this study was to determine whether the presence of pre-treatment PBE identifies IBD patients at risk for diminished anti-TNF treatment response. METHODS: We performed a registry analysis of IBD patients starting anti-TNF therapy who were enrolled in a consented, prospective, natural history IBD cohort at a tertiary center. Metadata was collected in the 2 years preceding and 2 years following anti-TNF initiation. The presence of PBE before and after anti-TNF initiation was recorded and treatment response was assessed for those with/without PBE using disease activity scores [Harvey Bradshaw Index (HBI) and Ulcerative Colitis Activity Index (UCAI)], quality of life measures [Short Inflammatory Bowel Disease Questionnaire (SIBDQ)], inflammatory markers (ESR, CRP), steroid use (prednisone or methylprednisolone), IBD-related hospitalizations, and IBD-related surgeries. Outcomes were assessed via linear mixed-effects and Cox proportional-hazards models for Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: A total of 580 IBD patients (CD 430, UC 150) were included with 111 (19%) demonstrating pre-treatment PBE (CD 66, UC 45). Table 1 summarizes demographic and clinical data. Following anti-TNF therapy, CD patients with pre-treatment PBE were more likely to have an IBD-related hospitalization [adjusted hazard ratio (AHR) 1.88, 95% CI 1.22-2.90, P = 0.004] and require anal fistula repair (AHR 3.88, 95% CI 1.09-13.8, P = 0.04) than CD patients without PBE. UC patients with pre-treatment PBE were more likely to have an elevated CRP following anti-TNF therapy (OR 2.77, 95% CI 1.50-5.10, P = 0.001) with a non-significant trend towards increased IBD-related admissions and surgeries. CD patients with pre-treatment PBE were less likely to require steroids following anti-TNF therapy than CD patients without PBE (AHR 0.40, 95% CI 0.18-0.86, P = 0.019). There was no significant difference in HBI, UCAI, or SIBDQ scores in patients with/without PBE undergoing anti-TNF therapy. CONCLUSION: Pre-treatment PBE identifies IBD patients at risk for worse outcomes following anti-TNF therapy, particularly in CD. Further studies are warranted to determine if alternate mechanism of action biologics will function optimally in the PBE IBD population.

P-056: Buccal epithelial cell chemokine release as a biomarker for clinical response to therapy in inflammatory bowel disease

BackgroundPatients with inflammatory bowel disease (IBD) who receive biologicals frequently experience lack or loss of response. Our aim was to describe the use and efficacy of biological therapy in a tertiary IBD center.MethodsWe included all bio-naive IBD patients who initiated biological therapy between 2010 and 2020 at our centre. Their medical records were reviewed.ResultsThe population consisted of 327 Crohn’s disease (CD) patients, 291 ulcerative colitis (UC) patients, and 3 patients with IBD unclassified (IBDU). The median follow-up was 3 years (interquartile range = 2–5) after initiating therapy. The annual number of patients initiating biological therapy rose from 29 (2010) to 85 (2019). Most patients (457, 73.6%) received 1 biological drug; 164 (26.4%) patients received 2 or more biologicals. Primary lack of response was observed in 36.4% (106/291) and 17.4% (57/327) of UC and CD patients; loss of response was observed in 27.1% (79/291) and 31.5% (103/327) of UC and CD patients, respectively. The 5-year surgery rates were 26.6% and 20.4% in UC and CD patients, respectively. Multivariate Cox regression showed that treatment with thiopurine reduced the likelihood of needing to switch biological therapy, requiring surgery or corticosteroids in UC patients (HR: 0.745, 95% CI: 0.559–0.993), but not in CD patients (HR: 0.996, 95% CI: 0.736–1.349).ConclusionsThe annual number of IBD patients initiated on biological therapy increased considerably between 2010 and 2020. One-quarter of these patients required surgery after 5 years. Our findings suggest a beneficial effect of concurrent thiopurines for UC patients receiving biologicals, but this was not found for CD patients. This effect in UC patients was not observed when we included patients initiating thiopurines up to 6 months after the introduction of biological therapy.

The incidence of inflammatory bowel disease (IBD) is increasing and the pathogenesis is still not completely understood. Micronutrients like vitamin D [25 (OH)D] and zinc play an important role in enzyme activities and the immune system. As the 25 (OH)D-receptor has been shown to be downregulated in patients with IBD, 25 (OH)D may emerge as a predictive marker for disease improvement. Studies on relationship of both micronutrients in IBD patients are lacking.We retrospectively evaluated serum levels of 25(OH)D and zinc together with baseline characteristics of 232 IBD patients. Uni- and multivariate analyses were performed for association between serum levels of 25(OH)D and zinc with clinical and deep remission (CR and DR).155 Crohn's disease (CD) and 77 ulcerative colitis (UC) patients were included. 54% (n = 125) and 6% (n = 14) of IBD patients showed deficient serum 25(OH)D levels below 20 ng/mL and zinc levels below 7 μmol/L. Serum 25(OH)D levels were significantly higher in IBD patients with CR (P = .02) and DR (P < .001) but not serum zinc levels, respectively. Serum 25(OH)D levels (P = .008), anti-tumor-necrosis-factor-α-trough-concentration (anti-TNF-α-TC) (P = .02) and CRP level (P = .02) were independently associated with CR in CD patients. Serum 25(OH)D threshold of 19 ng/mL discriminated CD patients with or without CR, having an area under the receiver operating curve analysis (AUROC) of 0.77 [95%-confidence interval (CI): 0.68–0.85]. In multivariate analysis serum 25(OH)D levels (P = .04) and anti-TNF-α-TC (P = .04) were associated with DR in CD patients. Serum 25(OH)D threshold of 26 ng/mL discriminated CD patients with or without DR, having an AUROC of 0.75 (95%-CI: 0.68–0.83).Serum 25(OH)D (P = .04) and fecal calprotectin levels (P = .04) were independently correlated with CR in UC patients. Serum 25(OH)D threshold of 32 ng/mL discriminated UC patients in CR with an AUROC of 0.83 (95%-CI: 0.71–0.95). Zinc levels did not correlate with disease activity status in CD or UC patients either.In conclusion, beside CRP and fecal calprotectin, serum 25(OH)D levels, but not serum zinc levels, may be an additional useful and noninvasive marker for characterizing different disease activity status of IBD patients. Measurement of serum 25(OH)D in IBD patients may be warranted. 25(OH)D supplementation in deficient IBD patients is recommended.

Objective To investigate the correlation of multidrug resistance gene 1 (MDR1),NR3C1 gene polymorphisms and clinical risk factors with efficacy,dependence,and resistance of glucocorticoid (GC) in patients with inflammatory bowel disease (IBD).Methods Anti coagulation blood samples of 196 healthy controls and 105 IBD patients received GC therapy were collected.There were 62 ulcerative colitis (UC) and 43 Crohn's disease (CD) in the IBD patients.The number of GC sensitive,GC dependent and GC resistant of UC patients were 36,13 and 13,respectively,and those of CD patients were 24,11 and eight.GC refractoriness included GC dependence and resistance.The genotype of MDR1 C3435T and NR3C1 Bcl Ⅰ of all the subjects was detected by the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR).The correlation between each genotype frequency,clinical features of patients with IBD and the efficacy of GC treatment was analyzed by Chisquare test,Fisher exact probability method or t test.Results Among UC patients,the disease course of GC refractory group and GC resistant group was longer than that of GC sensitive group ((6.660±1.523)years,(6.500±1.111) yearsvs (3.350±0.697) years,t=2.211,P=0.031; t=2.930,P=0.005).The serum level of C reaction protein (CRP) of GC refractory group was higher than that of GC sensitive group ((47.628±13.913) mg/Lvs (16.854±4.121) mg/L,t=2.121,P=0.047).The chronic relapse type was more common in GC refractory UC patients (Fisher exact probability method,P=0.035),and severe patients were more common in UC with GC resistance (Fisher exact probability method,P=0.021).The white blood cell count of GC resistant and GC refractory CD patient was lower than that of GC sensitive CD patients ((5.710 ± 0.604) ×109/L,(5.878±0.405) × 109/L vs (7.814 ±0.670) × 109/L,t=2.334,P=0.028; t=2.045,P=0.018).Patients with extraqntestinal manifestations was more common in CD with GC resistance (Fisher exact probability method,P=0.035).There was no statistically significant difference in the frequencies of MDR1 C3435T,NR3C1 Bcl Ⅰ genotypes,allelic genes and gene carrier among control group and GC sensitive dependent and resistant group of IBD patients.However,the frequency of MDR1 C3435T gene carrier was significantly different between GC sensitive group and GC refractory group,especially between GC sensitive group and GC resistance group (68.33％ vs 48.89％,x2 =4.051,P=0.044; 68.33％ vs 42.86％,x2 =4.274,P =0.039).Conclusions GC sensitivity of IBD patients with MDR1 C3435T loci T gene carrier was higher than that of IBD patients without T gene carrier.NR3C1 gene polymorphisms was not related with GC resistance and GC dependence.Compared with GC sensitive IBD patients,in GC resistant and GC dependent IBD pantient UC patients with long disease course,chronic relapse type,severe type,high level of CRP and CD patients with low white blood cell count and extra-intestinal manifestations were more common. Key words: Inflammatory bowel diseases; MDR1 gene; Receptors, glucocorticoid; Polymorphism,genetic

Covering the Cover

Smoking strongly affects the course of disease in patients with inflammatory bowel disease (IBD). Smoking is a risk factor for Crohn’s disease (CD) and worsens the course of the disease by increasing the rate of relapses, need for immunosuppressants and surgery. On the contrary, tobacco consumption is rather protective in ulcerative colitis (UC). Therefore, smoking cessation in CD leads to an early reduction of flares (in the first 3 months), a more benign course and less medical therapy.1,2 Our aim was to evaluate the effect of smoking cessation in UC and CD patients of the Swiss IBD Cohort study (SIBDCS). Adult IBD patients were prospectively included in the Swiss IBD cohort from November 2006 to November 2015. They were asked about their smoking status at enrolment and during the follow-up. We identified active smokers with a change of smoking status during follow-up suggesting a successful cessation of tobacco consumption and matched them to a group of patients continuing to smoke, A total of 2367 IBD patients (1368 CD, 999 UC) were included in the analysis. We identified 125 CD and 40 UC active smokers ceasing tobacco consumption during the follow-up there were matched to 214 CD and 50 UC smokers for gender, age at diagnosis and age. Among CD patients, smoking cessation was protective against the progression to fistulising disease (OR = 2.2, p < 0.05), whereas, there was no association with increasing numbers of flares, stenosing behaviour or surgeries. Among UC patients, persistent smokers developed more extra-intestinal manifestations than quitters (OR = 2.4, p = 0.09), this was also present at lower level in CD (OR = 1.2). Our findings in the Swiss IBD Cohort study are align with the literature: a reduction of the risk of fistulas among CD patients quitting smoking and the association between extraintestinal manifestations and aktive smoking status in IBD patients.3 1. Cosnes et al. Smoking cessation and the course of Crohn’s disease: an intervention study. Gastroenterology, 2011. 2. Nunes T, et al. Impact of smoking cessation on the clinical course of Crohn’s disease under current therapeutic algorithms: a multicenter prospective study. Am J Gastroenterol, 2016. 3. Severs M et al. Smoking is associates with extraintestinal manifestations in IBD. J Crohn Colitis, 2016.

The Commensal Microbiota and Enteropathogens in the Pathogenesis of Inflammatory Bowel Diseases

The preoperative use of anti-tumor necrosis factor-alpha (anti-TNF) in inflammatory bowel disease (IBD) patients undergoing surgery has been controversial due to concern for increased risks of postoperative complications. We aimed to determine the effect of preoperative anti-TNF therapy on postoperative complications in IBD patients undergoing abdominal surgery. A literature search of Google Scholar, PubMed, The Cochrane Library, EMBASE, and CINAHL was performed through October 2019. Studies reporting postoperative complication rates of Crohn's disease (CD), ulcerative colitis (UC), and IBD-unspecified patients with preoperative anti-TNF treatment undergoing abdominal surgery compared to controls without preoperative anti-TNF treatment were included. The main outcomes measured were overall, infectious, and noninfectious postoperative complications. Forty-one studies totaling 20 274 patients were included. There was a significant increase in overall complications in all patients treated with anti-TNF vs. controls [odds ratio (OR) = 1.13, 95% confidence interval (CI), 1.01-1.25, P = 0.03, I2 = 6%] with an absolute risk increase (ARI) of 5.5% and a number needed to harm (NNH) of 18. There was also a significant increase in infectious complications in CD patients (OR = 1.44; 95% CI 1.02-2.03, P = 0.04, I2 = 49%, ARI = 5.5%, NNH = 20) only. Contrastingly, there was a significant increase in noninfectious complications in all patients (OR = 1.44, 95% CI 1.13-1.85, P = 0.003, I2 = 8%, ARI = 6.4%, NNH = 16) and UC patients (OR = 1.57, 95% CI 1.15-2.14, P = 0.005, I2 = 25%, ARI = 8.5%, NNH = 12) only. Preoperative use of anti-TNF agents in IBD patients undergoing abdominal surgery is associated with increases in overall postoperative complications in all patients, infectious postoperative complications in CD patients, and noninfectious postoperative complications in UC patients.

Background Since approval, numerous inflammatory bowel disease (IBD) patients have been treated with subcutaneous (SC) infliximab (IFX), but real-life data based on a large multi-national population of patients switching from intravenous (IV) to SC IFX is lacking. Methods The ASSEMBLE project is an initiative to combine multi-national real-world cohort datasets and analyse the effectiveness and safety of SC IFX therapy. In the ASSEMBLE-1 analysis, three studies from France and the United Kingdom1-3 were integrated to assess the clinical outcomes up to 6 months (6M) after switching from IV to SC IFX. Clinical remission was defined as Harvey-Bradshaw Index (HBI) or modified HBI (mHBI) &amp;lt;5 for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) &amp;lt;3 for ulcerative colitis (UC). Treatment persistence was assessed by Kaplan-Meier survival analysis. Results The data of 428 patients were pooled from the three datasets (70.6% CD, 29.4% UC). 85.4% of patients were in clinical remission before switching with median HBI or mHBI of 1 (IQR 0,2) for CD and median SCCAI of 2 (IQR 1,3) or PMS of 0 (IQR 0,0) for UC. 59.6% of patients were treated with the standard dose of IV IFX (5 mg/kg Q8W) before switching and 54.0% of patients were on concomitant immunomodulator therapy. Patients were switched to SC IFX 120 mg Q2W (94.4%) or 120 mg QW (5.6%) regimen. After switching, the overall clinical remission rates were 83.4% and 84.7% at 3M and 6M, respectively. CD patients were associated with higher remission rate (89.8%) than UC patients (71.9%) at 6M (p&amp;lt;0.001). The disease activity scores and the levels of fecal calprotectin and C-reactive protein of the overall population were maintained stable after switching (Table 1). High persistence was observed in both CD (97.3% at 3M, 94.8% at 6M) and UC patients (96% at 3M, 94.1% at 6M), with no significant difference between indications (p=0.47 at 3M and p=0.78 at 6M). Perianal CD patients (n=89) did not have a significantly worse treatment persistence rate than non-perianal CD patients (p=0.30). The most common reasons leading to drug discontinuation were lost to follow-up, consent withdrawal, worsening of disease activity, and worsening of perianal disease (3 cases for each). Two patients discontinued due to injection-site pain. Conclusion This pooled analysis of ASSEMBLE-1 confirms that switching from IV to SC IFX is effective and safe for CD and UC patients in clinical practice and that the clinical remission is well maintained up to 6M after switching, with no new concerns in safety profiles. [1] Smith et al. J Crohns Colitis 2022 [2] Buisson et al. Clin Gastroenterol Hepatol 2023 [3] Rahmany et al. Gastroenterology 2023.

Characterization of Myeloid Neoplasms in Inflammatory Bowel Disease

Background Canada is among the countries with a high burden of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Extraintestinal manifestations (EIMs) incorporate a spectrum of systemic IBD-accompanying conditions that are associated with a poorer quality of life, higher disease activity, and increased need for IBD-related surgery and treatment escalation. Aims We aimed to establish the all-time and cumulative prevalence of EIMs in a large cohort of IBD patients and assess the risk factors associated with EIMs in IBD. Methods We conducted a retrospective cohort study of 7,150 IBD patients followed at the Division of Gastroenterology, University of Alberta, diagnosed between 1954–2022, with 159,026 person-years follow-up. Data were obtained via manual chart review, from electronic medical records and administrative reporting systems. The EIMs included ophthalmological, musculoskeletal, urogenital, hepatobiliary, dermatological, and pulmonary. Univariate and multivariate logistic regression models and cumulative prevalence curves with the Kaplan-Meier analysis were used. Results Data of 3,910 CD and 3,240 UC patients (50.3% females, median age 48.0 (range 17-98 y.o.)) were analyzed. Over one-third of IBD patients (34.0%) had at least one EIM. The EIMs prevalence did not differ significantly between CD and UC (34.8% vs. 33.0%; p=0.112). In CD patients, the most common EIM was scleritis/episcleritis (10.9%), followed by nephrolithiasis (10.1%) and axial spondyloarthritis (7.3%). The UC patients most frequently had scleritis/episcleritis (10.3%), primary sclerosing cholangitis (8.4%) and nephrolithiasis (7.8%). In CD patients, age at diagnosis ≥40 y.o. (OR 1.77, 95%CI 1.33-2.37), disease duration ≥20 years (OR 2.28, 95%CI 1.62-3.21) and C-reactive protein≥8.0 mg/L (OR 1.46, 95%CI 1.01-2.12) were independent risk factors for EIMs (Fig.1a). Among UC patients, the following EIM risk factors were identified: disease duration ≥20 years (OR 1.63, 95%CI 1.19-2.22), obesity (OR 1.40, 95%CI 1.04-1.89), vitamin B12 deficiency (OR 1.64, 95%CI 1.12-2.40), and need for IBD surgery (OR 1.63, 95%CI 1.13-2.34) (Fig.1b). Cumulative probability of EIMs in CD vs. UC was 8% vs. 12%, at 10 years, 27% vs. 38% at 20 years, and 51% vs. 59% at 30 years since diagnosis (Log-rank, pampersand:003C0.001) (Fig.1c). Conclusions Over one-third of IBD patients have at least one EIM and their pattern and cumulative prevalence varies substantially between CD and UC. It is important to be aware of the EIMs’ risk factors to recognize them early and provide adequate management aiming to decrease morbidity and mortality and improve the quality of life of IBD patients. Fig. 1a. Associations between demographic, phenotypic and clinical IBD features and EIMs among CD patients - results of the multivariate logistic regression analysis. Fig. 1b. Associations between demographic, phenotypic and clinical IBD features and EIMs among UC patients - results of the multivariate logistic regression analysis. Fig 1c. Cumulative prevalence of EIMs in CD (grey line) vs. UC (pink line). Funding Agencies None