Hashash, Jana G.

Abstract Background Complications such as intermittent pouchitis (IP) and chronic inflammatory disorders of the pouch (CP) are common after ileal pouch-anal anastomosis (IPAA), particularly among patients with both ulcerative colitis and primary sclerosing cholangitis (PSC). There are no standardized approaches for prophylaxis against these complications for patients with PSC undergoing IPAA. We compared outcomes among patients with PSC and IPAA who received antibiotic or immunosuppressive therapies to those who did not. Methods We designed a retrospective cohort study that included patients with ulcerative colitis and PSC from 7 tertiary care centers that underwent IPAA between 1994 and 2023. Patients were categorized on whether they received medications following IPAA that may provide primary prophylactic benefit, such as antibiotics, probiotics, immunomodulators, or biologic medications; and the proportion of patients developing IP and CP was evaluated. Results A total of 172 patients were included in the cohort, and 13 (7.6%) patients received antibiotics or immunosuppressant medications. Antibiotics and probiotics were the most common therapy (5 patients, 2.9%), followed by biologics, small-molecule inhibitors, immunomodulators, or mesalamine (all 1 patient, 0.6%). Compared to patients not receiving antibiotics or immunosuppression, patients receiving antibiotics or immunosuppression were significantly less likely to develop IP (69.2% vs 91.2%; P = .03; odds ratio 0.22; 95% CI, 0.06-0.80) and CP (23.1% vs 56.0%, P = 0.04; OR 0.24, 95% CI, 0.06-0.89). Conclusions In this retrospective cohort of patients with ulcerative colitis and PSC undergoing IPAA, usage of concomitant antibiotics or immunosuppression was low. However, use of concomitant antibiotics or immunosuppression may decrease the burden of inflammatory conditions of the pouch in these high-risk patients.

ABSTRACT Background Inflammatory bowel disease (IBD) and myeloproliferative neoplasms (MPNs) share chronic inflammation and immune dysregulation. Aim We evaluated the incidence of MPNs among patients with IBD and clinical outcomes of IBD–MPN coexistence. Methods Two retrospective cohort analyses were conducted using the TriNetX database. First, adults with ulcerative colitis (UC) or Crohn's disease (CD) were compared with matched non‐IBD controls to estimate incident MPN risk. A coexistence second analysis included patients with UC or CD who developed MPNs and then were matched to IBD without MPN controls to assess 5‐year outcomes, including IBD‐related complications, surgical interventions, colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). Medication subgroup analyses were performed to evaluate associations with MPN risk. Results After matching, 3873 patients with UC–MPN and 3474 patients with CD–MPN were included. Compared with matched non‐IBD controls, incident MPN risk was higher in UC (HR 1.60, p = 0.01) and CD (HR 1.56, p < 0.001). In CD, MPN coexistence was associated with higher risks of CRC (HR 1.52, p = 0.012), intestinal fistula (HR 2.84, p < 0.001), obstruction (HR 2.05, p < 0.001), perforation (HR 2.37, p < 0.001), small bowel resection (HR 3.69, p < 0.001) and colectomy (HR 2.10, p < 0.001). In UC, MPN coexistence was associated with higher risks of CRC (HR 1.50, p = 0.001), PSC (HR 1.75, p = 0.03) and pouchitis (HR 1.68, p = 0.003). Exposure to thiopurines (HR 1.28, p < 0.001) was associated with increased MPN risk, whereas TNF, IL‐23 and JAK inhibitors were not. Conclusions IBD is associated with increased MPN risk, and IBD–MPNs coexistence is associated with worse IBD‐related complications and malignancy risk.

Background: Perianal Crohn’s disease (PCD) is a severe and disabling phenotype of Crohn’s disease that often requires multidisciplinary medical and surgical management. Although ustekinumab (UST) and vedolizumab (VDZ) are widely used after antitumor necrosis factor (anti-TNF) failure, direct comparative data specifically in PCD remain limited. Methods: We conducted a multicenter, retrospective cohort study using the TriNetX US Collaborative Network to compare the effectiveness of UST versus VDZ in adults (18 y or older) with PCD between January 2017 and May 2023. Outcomes were perianal-specific clinical events, including definitive fistula surgery, incision and drainage, diversion procedures, and antibiotic use (metronidazole or ciprofloxacin), assessed at 1 and 2 years after biological initiation. Propensity score matching (PSM) (1:1) was performed to balance baseline variables. Time-to-event analyses were conducted in the matched population using Kaplan–Meier methods, and hazard ratios (HRs) were estimated using Cox proportional hazards models within the matched cohorts. Results: A total of 2936 patients were identified before PSM: 1997 patients in the UST group and 939 patients in the VDZ group. After PSM, 936 patients were included in each cohort. In the matched cohorts, UST was associated with significantly lower risk of definitive perianal fistula surgery (HR: 0.66, 95% CI: 0.50-0.89; P <0.01), and composite surgical events (HR: 0.70, 95% CI: 0.54-0.87; P <0.01) compared with VDZ at 1 year. Rates of antibiotic use, incision and drainage of perianal abscess, and diversion procedures were numerically lower but not statistically significant. At 2 years, these findings persisted, with significantly lower cumulative incidence of definitive perianal fistula surgery (HR: 0.78, 95% CI: 0.61-0.90; P =0.03), composite surgical events (HR: 0.81, 95% CI: 0.69-0.90; P <0.01), and antibiotic use (HR: 0.86, 95% CI: 0.75-0.93; P =0.04) in the UST cohort compared with VDZ. Rates of incision and drainage and diversion procedures remained similar between groups. Conclusion: In this large real-world cohort, UST was associated with lower risks of perianal surgical interventions at one and two years and reduced antibiotic utilization at two years compared with VDZ in patients with PCD. These findings highlight meaningful differences in real-world effectiveness between therapies and support the need for prospective studies to further evaluate comparative effectiveness in this population.

Abstract Summary A retrospective cohort study of 113,729 IBD patients with low cardiovascular (CV) risk using the US National TriNetX database. Anti-TNF and anti-integrin therapies were linked to reduced major adverse cardiovascular events (MACE), while JAK inhibitors showed no increased risk. Background Due to underlying chronic inflammation, inflammatory bowel disease (IBD) is associated with an increased risk of major adverse cardiovascular events (MACE). There is limited data on the role of cardiovascular (CV) risk factors and IBD medications on MACE. We aim to determine the association between MACE and IBD medications in a large national cohort of IBD patients with low baseline CV risk. Methods We conducted a retrospective cohort study between January 1, 2015—November 15, 2023 using the TriNetX database. Using logistic regression analysis, IBD patients exposed to biologics and small molecules were assessed for outcomes of individual and composite MACE [myocardial infarction (MI), ischemic stroke, percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG)]. Outcomes were adjusted for demographics, non-advanced IBD therapies, statin use, CV risk factors, and prior history of coronary artery disease (CAD). Results We identified 113,729 IBD patients with an average age of 42 years and low prevalence of CV risk factors (5-6%). Anti-TNF therapy was associated with a statistically significant decreased risk of composite MACE [adjusted OR (aOR) 0.795, 95% CI 0.670-0.930, p = 0.005] and PCI/CABG [aOR 0.56, 95% CI 0.274-0.562, p = 0.002] and anti-integrin therapy was associated with a decreased risk of composite MACE [aOR 0.76, 95% CI 0.580-0.980, p = 0.035]. Anti-IL12/23 and JAK inhibitors showed no increased risk of MACE. Conclusion In a cohort of young IBD patients with low CV risk, use of anti-TNF and anti-integrins is associated with a decreased risk of MACE and there was no increased risk of MACE with JAK inhibitors.

Patients with inflammatory bowel disease (IBD) frequently modify their diet and use complementary medicine, but inconsistent evidence and persistent myths complicate clinical guidance. Our aim was to critically evaluate the evidence for dietary and complementary strategies in IBD and to clarify common misconceptions, supporting evidence-based, patient-centred management. A narrative synthesis of randomised trials, systematic reviews and international guidelines was conducted. Interventions that were evaluated included dietary strategies encompassing the Mediterranean diet, low-FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) diet, exclusive enteral nutrition, Crohn’s disease exclusion diet and the specific carbohydrate diet. Other interventions included complementary modalities such as probiotics, curcumin, herbal medicine, mind-body interventions and physical activity. The Mediterranean diet shows moderate evidence for improving quality of life and inflammatory biomarkers. A low-FODMAP diet can relieve functional symptoms but does not reduce inflammation. Exclusive enteral nutrition remains first-line induction therapy in paediatric Crohn’s disease. The Crohn’s disease exclusion diet/partial enteral nutrition shows promise in adults. Among complementary therapies, specific probiotics and curcumin demonstrate benefits in certain cases of ulcerative colitis, but evidence for their use in Crohn’s disease remains limited. Personalised, multidisciplinary supervised dietary and complementary approaches may support symptom control and quality of life in IBD patients. However, they should complement rather than replace evidence-based pharmacologic therapy, and high-quality trial and clinical studies are needed to define optimal, evidence-based nutritional strategies.

Abstract Inflammatory bowel diseases (IBD), comprising Crohn’s disease and ulcerative colitis, are chronic, inflammatory, immune mediated, relapsing-remitting conditions of the gastrointestinal tract with multidimensional and often negative effects on patients’ quality of life. The global burden of IBD is increasing and is forecast to affect 1% of the population in early industrialized nations over the next 10 years. Advances in our understanding of the causes and pathogenesis of IBD in the past three decades have translated into new treatments that modulate the immune inflammatory cascade. Modern goals of treatment are clinical remission through assessment of patient reported outcomes and deep remission defined as mucosal healing on colonoscopy or imaging. Achieving both clinical and deep remission affords patients a better long term prognosis and quality of life. This review summarizes the latest evidence on IBD diagnosis, staging, and prognosis, with a detailed focus on current treatments.

Abstract Introduction There are limited data on the impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) on the risk of recurrent pouchitis after ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC). Methods A retrospective cohort study was conducted in the TriNetX Research Network in adult patients with obesity and IPAA for UC with a history of pouchitis in whom a GLP-1RA was initiated compared to those patients in whom a GLP-1RA was not initiated. The primary outcome was the risk of recurrent pouchitis within 12 months. The secondary outcomes were mean number of antibiotic prescriptions, anti-diarrheal medication use, Crohns-like disease of pouch (CLDP), and pouch excision. One-to-one propensity score matching was performed. Results We identified 43 UC-IPAA patients with obesity and history of pouchitis (mean age 51.7 ± 14.7 years, mean body mass index [BMI] 34.4 ± 6 kg/m2, 60.4% female). After propensity score matching, the GLP-1RA cohort had a significantly decreased risk of recurrent pouchitis (26.3% vs 52.6%; adjusted odds ratio [aOR], 0.32; 95% CI, 0.12-0.84) compared to the control cohort. Mean antibiotic prescriptions were numerically lower in the GLP-1RA cohort (2 vs 4.4, P = .16). Anti-diarrheal medication use was lower in the GLP-1RA cohort (18.4% vs 47.3%; aOR, 0.23; 95% CI, 0.07-0.67). There was no difference in the risk of CLDP. Zero patients required pouch excision in both cohorts. Conclusion Our study in a small cohort of patients with UC-IPAA and obesity with a history of pouchitis showed that GLP-1RA use was associated with decreased risk of recurrent pouchitis and anti-diarrheal medication use.

Lay Summary In this study we evaluated the effectiveness of vedolizumab (anti-integrin) vs ustekinumab/risankizumab (anti-interleukin) therapy for isolated small-bowel Crohn’s disease using a real-world, multicenter national database. We found that anti-interleukin therapy was more effective for inducing steroid-free remission and reducing hospitalizations.

Abstract Background Prior studies have examined small intestinal dysplasia and cancer in Crohn’s disease; however, there is limited information on ulcerative colitis (UC). We describe characteristics of small intestinal dysplasia and cancer in patients with UC. In this study, we aimed to identify common characteristics between patients with UC that were diagnosed with small intestinal malignancy. Methods Electronic medical records were reviewed for 3 tertiary referral centers to identify patients with a diagnosis of UC and small intestinal dysplasia or cancer between 2010 and 2023. Data collection included demographics, family history of gastrointestinal malignancy, UC diagnosis date, duration and location of disease, prior UC medical treatment or surgery, diagnosis of primary sclerosing cholangitis (PSC), PSC-related complications, and details of cancer or dysplasia. Descriptive statistics were performed. Results Thirty-five patients (60% male, mean age of diagnosis 39.3 ± 21.5 years old) were identified with UC and subsequent small intestinal dysplasia or cancer. Most had pancolitis (74.3%) or pancolitis with backwash ileitis (8.57%). Half underwent surgery for their UC, and half of these had the cancer or dysplasia found at the time of surgery. Ileal dysplasia was found in 2 patients (5.71%), duodenal adenocarcinoma in 2 (5.71%), ileal adenocarcinoma 2 (5.71%), duodenal carcinoid in 4 (11.4%), ileal carcinoid in 24 (68.6%), other duodenal neuroendocrine tumor in 1 (2.86%). Primary sclerosing cholangitis was diagnosed in 5 patients (14%), and 3 required liver transplants. Conclusions Small intestinal dysplasia and cancer are rare in this population. Most patients with small intestinal cancer or dysplasia were male, Caucasian, and had a history of extensive colitis. Ileal carcinoid had the highest incidence. Gastroenterologists should be aware of this finding in patients with UC.

ABSTRACT Introduction Patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the risk of CRC in patients with PSC without IBD remains uncertain. We aimed to evaluate the risk of CRC in patients with PSC without a history of IBD using a large national database. Methods We conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18 years with PSC. Patients were then divided into two groups, PSC with IBD (PSC‐IBD cohort) and PSC without IBD (PSC non‐IBD cohort), and were matched with patients without a history of PSC or IBD (non‐PSC/non‐IBD group) by using 1:1 propensity score matching. The primary outcome was the risk of first diagnosis of CRC. With censoring applied, Kaplan–Meier analysis with hazard ratios (HRs) and 95% CIs was used to compare time‐to‐event rates at daily time intervals. Results PSC patients without IBD were at increased risk of CRC compared to the non‐PSC/IBD cohort (aHR = 2.91; 95% CI: 1.6–6.0). Patients with PSC and IBD exhibited a higher risk of CRC (aHR = 6.5; 95% CI: 3.78–11.2), especially among the UC cohort (aHR = 6.3; 95% CI: 3.2–12.4). Patients with PSC were at increased risk of various gastrointestinal malignancies (aHR = 10.5; 95% CI: 7.3–15; p < 0.0001), including hepatobiliary cancers, pancreatic cancer, and hepatocellular carcinoma. Discussion Our findings provide real‐world evidence that PSC is an independent risk factor for colorectal cancer, even in the absence of concomitant IBD. These results support the need for further research to determine whether patients with isolated PSC may benefit from tailored CRC surveillance strategies.