Kochhar, Gursimran S

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 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.

Abstract Background Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for medically refractory inflammatory bowel disease (IBD). In this systematic review and meta-analysis, we assess outcomes and safety of endoscopic balloon dilatation (EBD) for IPAA strictures. Methods A systematic search of numerous databases was performed through June 2023 to identify studies reporting on the outcomes of EBD in pouch-related strictures. Outcomes included technical success, clinical success at index dilation and in pouch retention, recurrence of symptoms post-EBD, and adverse events of EBD. Meta-analysis was performed using a random-effects model, and results were expressed in terms of pooled rates along with relevant 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran Q statistical test with I2 statistics. Results Seven studies with 504 patients were included. The pooled rate of technical success and clinical success of index dilatation was 98.9% (95% CI, 94.8-99.8%; I20%) and 30.2% (95% CI, 7.1-71%; I20%), respectively. The pooled rate of clinical success in pouch retention without the need for additional surgery was 81.4% (95% CI, 69.6-89.3%; I272%). The pooled failure rate of EBD was 18.6% (95% CI, 10.7-30.4%, I272%). The pooled rate of recurrence of symptoms after index dilatation was 58.9% (95% CI, 33.3-80.5%; I213%). The pooled rate of serious adverse events was 1.8% (95% CI, 1-3.5%, I20%). No deaths related to EBD were reported. Conclusions Endoscopic balloon dilatation is safe and highly effective for management of IPAA strictures. Additional studies are needed to compare its efficacy with surgical interventions.

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.

LINKED CONTENTThis article is linked to Kochhar et al papers. To view these articles, visit https://doi.org/10.1111/apt.17570 and https://doi.org/10.1111/apt.17697

SummaryBackgroundThere is limited real‐world data on comparative effectiveness of different biologic or small molecule agents as second‐line therapies in patients with ulcerative colitis (UC) with prior exposure to a tumour necrosis factor inhibitor (TNFi).MethodsWe conducted a retrospective cohort study using TriNetX, a multi‐institutional database to assess the efficacy of tofacitinib, vedolizumab and ustekinumab in patients with ulcerative colitis (UC) with prior exposure to a TNFi. Failure of medical therapy was defined as a composite outcome of intravenous steroids or colectomy within 2 years. One‐to‐one propensity score matching was performed for demographics, disease extent, mean haemoglobin, C‐reactive protein, albumin and calprotectin, prior IBD medications and steroid use between cohorts.ResultsAmong 2141 patients with UC and prior exposure to TNFi, 348 (16.2%), 716 (33.4%) and 1077 (50.3%) were switched to tofacitinib, ustekinumab and vedolizumab, respectively. After propensity‐score matching, there was no difference in the composite outcome (aOR: 0.77, 95% CI: 0.55–1.07) but higher risk of colectomy (aOR: 2.69, 95% CI: 1.31–5.50) in the tofacitinib cohort than the vedolizumab cohort. There was no difference in the risk of composite outcome (aOR: 1.29, 95% CI: 0.89–1.86) but higher risk of colectomy (aOR: 2.63, 95% CI: 1.24–5.58) in the tofacitinib cohort than the ustekinumab cohort. The vedolizumab cohort had a higher risk of composite outcome (aOR: 1.67, 95% CI: 1.29–2.16) than the ustekinumab cohort.ConclusionUstekinumab might be the preferred second‐line therapy over tofacitinib and vedolizumab in patients with UC that were previously exposed to a TNFi.

AbstractIntroductionThere are concerns regarding the effectiveness and safety of SARS‐CoV‐2 vaccine in inflammatory Bowel Disease (IBD) patients. This systematic review and meta‐analysis comprehensively summarises the available literature regarding the safety and effectiveness of SARS‐CoV‐2 vaccine in IBD.MethodsThree independent reviewers performed a comprehensive review of all original articles describing the response of SARS‐CoV‐2 vaccines in patients with IBD. Primary outcomes were (1) pooled seroconversion rate SARS‐CoV‐2 vaccination in IBD patients (2) comparison of breakthrough COVID‐19 infection rate SARS‐CoV‐2 vaccination in IBD patients with control cohort and (3) pooled adverse event rate of SARS‐CoV‐2 vaccine. All outcomes were evaluated for one and two doses of SARS‐CoV‐2 vaccine. Meta‐regression was performed. Probability of publication bias was assessed using funnel plots and with Egger’s test.ResultsTwenty‐one studies yielded a pooled seroconversion rate of 73.7% and 96.8% in IBD patients after one and two doses of SARS‐CoV‐2 vaccine respectively. Sub‐group analysis revealed non‐statistically significant differences between different immunosuppressive regimens for seroconversion. Meta‐regression revealed that the vaccine type and study location independently influenced seroconversion rates. There was no statistically significant difference in breakthrough infection in IBD patients as compared to control after vaccination.ConclusionIn summary, the systematic review and meta‐analysis suggest that SARS‐CoV‐2 vaccine is safe and effective in IBD patients.

SummaryBackgroundAccurate estimates for the risk of COVID‐19 in IBD, and an understanding of the impact of COVID‐19 on IBD course and the risk of incident post‐infectious IBD are needed.AimsTo estimate the risk of COVID‐19 in IBD and study its impact on IBD course and the risk of incident post‐infectious IBD.MethodsA retrospective propensity score matched cohort study utilising multi‐institutional research network TriNetX. COVID‐19 patients with and without IBD were identified to quantify the risk of COVID‐19 in patients with IBD, COVID‐19 outcomes in patients with IBD and the impact of COVID‐19 on IBD disease course. The risk of incident post‐infectious IBD in COVID‐19 patients was compared to the population not infected with COVID‐19 during a similar time period.ResultsIncidence rate ratio for COVID‐19 was lower in IBD patients compared to the non‐IBD population (0.79, 95% CI: 0.72‐0.86). COVID‐19‐infected patients with IBD were at increased risk for requiring hospitalisation compared to non‐IBD population (RR: 1.17, 95% CI: 1.02‐1.34) with no differences in need for mechanical ventilation or mortality. Patients with IBD on steroids were at an increased risk for critical care need (RR: 2.22, 95% CI: 1.29‐3.82). Up to 7% of patients with IBD infected with COVID‐19 suffered an IBD flare 3‐months post‐infection. Risk for incident IBD post‐COVID was lower than that seen in the non‐COVID population (RR: 0.64, 95% CI: 0.54‐0.65).ConclusionWe observed no increase in risk for COVID‐19 amongst patients with IBD or risk for de novo IBD after COVID‐19 infection. We confirmed prior observations regarding the impact of steroid use on COVID‐19 severity in patients with IBD.

SummaryBackgroundAn association between bariatric surgery and development of de‐novo inflammatory bowel disease (IBD) has been observed.AimTo evaluate further the association among bariatric surgery, weight loss medications, obesity and new‐onset IBD.MethodsUsing Explorys, a population‐based Health Insurance Portability and Accountability Act compliant database, we estimated the prevalence of de‐novo IBD among patients treated with bariatric surgery (Roux‐en‐Y gastrojejunostomy, laparoscopic sleeve gastrectomy or gastric banding) (n = 60 870) or weight loss medications (orlistat, phentermine/topiramate, lorcaserin, bupropion/naltrexone and liraglutide) (n = 193 790) compared with obese controls (n = 5 021 210), between 1999 and 2018.ResultsThe prevalence of de‐novo IBD was lower among obese patients exposed to bariatric surgery (7.72 per 1000 patients) or weight loss medications (7.22 per 1000 patients) compared with patients with persistent obesity not exposed to these interventions (11.66 per 1000 patients, P < 0.0001). The risk reduction for de‐novo IBD was consistent across bariatric surgeries and weight loss medications with the exception of orlistat which was not associated with a reduction in risk for de‐novo IBD compared with the persistent obese control cohort.ConclusionObese patients undergoing treatment with bariatric surgery or weight loss medications are at a lower risk for developing de‐novo IBD compared with persistently obese controls not exposed to these interventions. These data suggest that obesity and ineffective management of obesity are risk factors for de‐novo IBD. Further research is needed to confirm these observations and understand potential mechanisms.