Desai, Aakash

Abstract Background Appendectomy has been proposed to influence ulcerative colitis (UC) outcomes, but its effect based on timing before or after diagnosis and long-term UC outcomes remains unclear. Materials and Methods Using TriNetX U.S. Collaborative Network, we identified adults with UC (2010-2024) who underwent appendectomy before or after diagnosis. Two 1:1 propensity score-matched comparisons were performed: appendectomy-before-UC and appendectomy-after-UC versus controls. The primary outcome was a 5-year composite of oral/intravenous (IV) corticosteroid use or colectomy. Secondary outcomes included individual composite outcomes and advanced therapy initiation in biologic-naive patients. Subgroup analyses stratified by age and biologic exposure were also performed. Results After matching, appendectomy after UC diagnosis showed no association with the composite outcome (aHR 0.98, 95% CI, 0.83-1.16), oral steroids (aHR 0.90, 95% CI, 0.75-1.09), IV steroids (aHR 1.11, 95% CI, 0.87-1.43), colectomy (aHR 1.24, 95% CI, 0.77-1.99), or advanced therapy initiation (aHR 0.97, 95% CI, 0.63-1.48). Appendectomy before UC diagnosis also showed no difference in the composite outcome (aHR 0.91, 95% CI, 0.76-1.09), oral steroids (aHR 0.88, 95% CI, 0.72-1.08), colectomy (aHR 0.99, 95% CI, 0.60-1.63), or advanced therapy initiation (aHR 0.77, 95% CI, 0.53-1.13). However, IV steroid use was reduced (aHR 0.68, 95% CI, 0.51-0.90, P = .006). In subgroup analyses, advanced therapy initiation was lower in patients aged 18-40 years following appendectomy after UC diagnosis (aHR 0.56, 95% CI, 0.33-0.96, P = .03). Conclusion Appendectomy was not associated with improved long-term UC outcomes of oral/IV steroid use, colectomy or initiation of advanced therapy regardless of timing.

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 Background and Aims Seven new advanced therapies, belonging to three new classes, have been approved for the treatment of inflammatory bowel diseases (IBD) since 2021. We examined trends in utilization of advanced therapies in the USA since 2021. Methods Using de-identified electronic health record data from 71 US health systems, we examined quarterly trends in utilization of different advanced therapies in patients with ulcerative colitis and Crohn’s disease between 2021 and 2025, using interrupted time-series analysis utilizing Prais–Winsten regression. Results In 11 093 patients with ulcerative colitis treated with advanced therapies, we observed an increase in use of upadacitinib (12.1% in Q2/2025; P < .001, compared with first quarter of prescription), interleukin-23p19 (IL23p19) antagonists (5.5%; P = .03), and ustekinumab (9.5%; P = .04), decline in use of tumor necrosis factor (TNF) antagonists (34.5%; P = .003), and stable use of vedolizumab (33.6%; P = .17) and sphingosine-1 phosphate receptor modulators (1.6%; P = .28). In 15 951 patients with Crohn’s disease treated with advanced therapies, we observed an increase in use of IL23p19 antagonists (15.0% in Q1/2025; P = .003) and upadacitinib (5.9%; P < .001) and decline in use of TNF antagonists (50.2%; P = .001) and ustekinumab (13.5%; P < .001). Conclusions Contemporary trends in advanced therapy utilization in patients with IBD suggest an increased utilization of upadacitinib and anti-interleukins, accompanied by a decline in use of TNF antagonists in the USA.

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.

Summary Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) show anti‐inflammatory properties. Aim To evaluate their clinical impact on inflammatory bowel disease (IBD) outcomes. Methods Retrospective cohort study utilising the TriNetX database comparing IBD‐specific outcomes in patients with ulcerative colitis (UC) or Crohn's disease (CD) and type 2 diabetes mellitus (T2DM) on GLP‐1RA compared to oral hypoglycaemic agents. The primary outcome was hospitalisation requiring intravenous steroids and IBD‐related surgery within 3 years. We performed 1:1 propensity score matching (PSM) for demographics, co‐morbid conditions, BMI, laboratory values, HbA1c, and IBD medications including steroids. Results We identified 1130 patients in the UC GLP‐1RA cohort (mean age: 58.9 ± 11.6 years, 56.3% female, 70.2% White, 57.2% with obesity) and 1140 patients in the CD GLP‐1RA cohort (mean age: 56.7 ± 11.5, 61.9% female, 73.6% White, 56.2% with obesity). After PSM, there was no difference in the risk of intravenous steroid use (aHR: 1.21, 95% CI: 0.92–1.59) but a lower risk of colectomy (aHR: 0.37, 95% CI: 0.14–0.97) between the UC GLP‐1RA and control cohort. There was no difference in the risk of intravenous steroid use (aHR: 1.04, 95% CI: 0.80–1.34) but a lower risk of surgery (aHR: 0.55, 95% CI: 0.36–0.84) between the CD GLP‐1RA and CD control cohort. There was no difference in the risk of oral steroid use or advanced therapy initiation in the UC and CD GLP‐1RA than control cohorts. Conclusions We found an association between lower risk of IBD‐related surgery and GLP‐1RA use for T2DM in patients with UC or CD.

INTRODUCTION: There are limited data regarding the natural history after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The principal objectives of this study were to identify 4 key outcomes in the natural history after IPAA within 1, 3, 5, and 10 years: the incidence of pouchitis, Crohn's-like disease of the pouch, use of advanced therapies after IPAA, and pouch failure requiring excision in a network of electronic health records. METHODS: We performed a retrospective cohort study in TriNetX, a research network of electronic health records. In addition to evaluating incidence rates, we also sought to identify factors associated with pouchitis and advanced therapy use within 5 years of IPAA after 1:1 propensity score matching, expressed as adjusted hazard ratios (aHRs). RESULTS: Among 1,331 patients who underwent colectomy with IPAA for UC, the incidence of pouchitis increased from 58% in the first year after IPAA to 72% at 10 years after IPAA. After propensity score matching, nicotine dependence (aHR 1.61, 95% confidence interval [CI] 1.19–2.18), antitumor necrosis factor therapy (aHR 1.33, 95% CI 1.13–1.56), and vedolizumab prior to colectomy (aHR 1.44, 95% CI 1.06–1.96) were associated with an increased risk of pouchitis in the first 5 years after IPAA. The incidence of Crohn's-like disease of the pouch increased to 10.3% within 10 years of IPAA while pouch failure increased to 4.1%. The incidence of advanced therapy use peaked at 14.4% at 10 years after IPAA. DISCUSSION: The incidence of inflammatory conditions of the pouch remains high in the current era, with 14% of patients requiring advanced therapies after IPAA.