Khataniar, Himsikhar

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.

Abstract Introduction Limited data exist on the natural history and treatment persistence in ulcerative colitis (UC) patients on 5-aminosalicylic acid (5-ASA) in the era of biologic agents and small molecules. Methods This was a retrospective cohort study utilizing the US Collaborative Network in patients with UC who were initiated on 5-ASA between 2015 and 2019. The 1-, 3-, and 5-year incidence rates of advanced therapy use and colectomy were calculated. Predictors of advanced therapy use and colectomy within 5 years were analyzed and expressed as adjusted odds ratios (aORs) with 95% confidence intervals (CIs) after 1:1 propensity score matching (PSM). Results Among 15 177 patients in the UC 5-ASA cohort (mean age 47.2 ± 19.1 years old, 49.2% female and 70.3% White), the 1-, 3- and 5-year incidence of advanced therapy use was 5.37%, 11.56% and 15.8%, respectively. After PSM, age < 40 years old (aOR 1.93, 95% CI, 1.73-2.15), male sex (aOR 1.13, 1.02-1.25), obesity (aOR 1.18, 95% CI, 1.05-1.31), pancolitis (aOR 1.18, 95% CI, 1.03-1.36), steroid use (aOR 1.79, 95% CI, 1.53-2.09), and CRP ≥ 12 mg/L (aOR 1.39, 95% CI, 1.05-1.83) prior to 5-ASA initiation were associated with advanced therapy use within 5 years. The 1-, 3- and 5-year incidence of colectomy was 0.74%, 1.28%, and 1.64% respectively. After PSM, male sex (aOR 1.36, 95% 1.06-1.74), obesity (aOR 1.32, 95% CI, 1.02-1.69), primary sclerosing cholangitis (aOR 2.37, 95% CI, 1.11-5.06), pancolitis (aOR 1.90, 95% CI, 1.29-2.78), and steroid use (aOR 1.96, 95% CI, 1.35-2.84) were associated with colectomy within 5 years. Conclusion Our study provides updated estimates of advanced therapy utilization and colectomy as well as predictors of disease progression in patients with UC on 5-ASA in the biologic era.

ABSTRACT Background Obesity has been linked to a more severe phenotype in patients with ulcerative colitis (UC). Aim To evaluate the impact of obesity on outcomes of advanced therapies in UC. Methods We conducted a retrospective cohort study utilising the TriNetX database comparing the composite score of corticosteroid use, change in advanced therapy or colectomy within two years between two cohorts of patients with UC—those with obesity (BMI ≥ 30 kg/m 2 ) and those without (BMI 18.5–24.9). The risk assessment was stratified to specific advanced therapies, including tumour necrosis factor α inhibitors (TNFi), vedolizumab, ustekinumab and Janus kinase inhibitors (JAKi). We performed 1:1 propensity score matching (PSM) for demographics, co‐morbid conditions, laboratory values and IBD medications including corticosteroids. Results There were 3904, 2025, 1150 and 477 patients on TNFi, vedolizumab, ustekinumab and JAKi, respectively, in the UC obesity cohort. After PSM, the UC obesity cohort was at an increased risk of the composite outcome of corticosteroid use, change in therapy and colectomy compared to the UC control cohort in patients on TNFi (aHR 1.37, 95% CI 1.29–1.49), vedolizumab (aHR 1.29, 95% CI 1.16–1.43), ustekinumab (aHR 1.1.26, 95% CI 1.10–1.44) and JAKi (aHR 1.38, 95% CI 1.13–1.69). Sub‐group analysis based on the specific TNFi also showed an increased risk of composite outcome for infliximab (aHR 1.36, 95% CI 1.22–1.52) and adalimumab (aHR 1.26, 95% CI 1.11–1.42) within 2 years. Conclusions Obesity is associated with lower efficacy of several advanced therapies in patients with UC.

Abstract Introduction There is limited real-world evidence comparing the effectiveness of ozanimod to vedolizumab as first-line advanced therapies in patients with ulcerative colitis (UC). Methods We conducted a retrospective cohort study using TriNetX, a multi-institutional US database in adults with UC who were initiated on ozanimod compared to vedolizumab between January 1, 2021 and 22 June, 2024. The primary outcome was to compare the risk of a composite outcome of corticosteroid use, colectomy, or change to another advanced therapy between the 2 cohorts within 12 months. 1:1 propensity score matching (PSM) was performed for demographics, comorbid conditions, disease extent, laboratory parameters, and previous corticosteroid use. The risk was expressed as an adjusted odds ratio (aOR) with 95% CIs. Results We identified 222 patients in the ozanimod cohort (mean age 41.2 ± 15.7, 46.3% male sex, 68% White, and 22.5% ulcerative proctitis), and 4145 patients in the vedolizumab cohort (mean age 47.4 ± 18.3, 45.2% male sex, 69.7% White, and 17.2% ulcerative proctitis). After PSM, there was no significant difference in the risk of the composite outcome (aOR 0.92, 95% CI, 0.63-1.36) and corticosteroid use (aOR 0.80, 95% CI, 0.53-1.18) between the 2 cohorts within 12 months. There was a higher risk of change in therapy in the ozanimod cohort (aOR 1.95, 95% CI, 1.09-3.49) compared to the vedolizumab cohort. Colectomy rates were low in both cohorts (<0.04%). Conclusions Our real-world study showed that ozanimod use is associated with similar corticosteroid use but higher odds of a change in therapy compared to vedolizumab when used as first-line therapy in patients with UC. Further prospective studies are needed to understand long-term outcomes.

INTRODUCTION: There are limited real-world data comparing the effectiveness of upadacitinib and tofacitinib in patients with ulcerative colitis (UC). METHODS: We conducted a retrospective cohort study using TriNetX, a multi-institutional database, to compare the effectiveness of upadacitinib and tofacitinib in patients with UC. The primary aim was to assess the risk of a composite outcome of hospitalization requiring intravenous steroids and/or colectomy within 6 and 12 months. One-to-one propensity score matching was performed for demographics, comorbid conditions, mean hemoglobin, C-reactive protein, albumin, and calprotectin, and prior UC medications including recent oral or intravenous steroid use between the cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULTS: There were 526 patients in the upadacitinib cohort (mean age 40.4 ± 16.3, 44.8% female sex, 76.6% White race) and 1,149 patients in the tofacitinib cohort (mean age 42 ± 17.1, 41.9% female sex, 76% White race). After propensity score matching, there was no significant difference in the risk of the composite outcome of need for intravenous steroids and/or colectomy within 6 months (aOR 0.75, 95% CI 0.49–1.09). However, there was a lower risk of the composite outcome (aOR 0.63, 95% CI 0.44–0.89) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. There was no difference in the risk of intravenous steroid use (aOR 0.70, 95% CI 0.48–1.02) but lower risk of colectomy (aOR 0.46, 95% CI 0.27–0.79). In sensitivity analysis, there was also a lower risk of the composite outcome (aOR 0.64, 95% CI 0.44–0.94), including lower risk of intravenous steroid use (aOR 0.67, 95% CI 0.45–0.99) and colectomy (aOR 0.49, 95% CI 0.26–0.92) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. DISCUSSION: This study utilizing real-world data showed that upadacitinib was associated with improved disease-specific outcomes at 12 months compared with tofacitinib in patients with UC.