Farraye, Francis A.

Abstract Introduction The objective of the study was to investigate the characteristics of patients who underwent surgery for dysplasia detected during chromoendoscopy (CE) surveillance for inflammatory bowel disease (IBD) and the incidence of cancer in the surgical specimen. Methods A retrospective review of medical records of all patients with dysplasia on a background of underlying IBD diagnosed through CE was carried out at a tri-site enterprise tertiary referral center between 2006 and 2019. We aimed to assess the clinical characteristics of patients requiring surgery for dysplasia and the incidence of cancer in the surgical specimen. Results Out of 219 patients with dysplasia on CE, 35 underwent surgery for dysplasia (16%). Indications for surgery were multifocal disease (n = 6), endoscopically unresectable lesions (n = 13), visible HGD (n = 7) and unifocal invisible LGD (n = 9). Out of 35 patients requiring surgery, 5 were found to have adenocarcinoma, one of whom with stage IIIB disease received postoperative chemotherapy. No patient with a pathologic diagnosis of adenocarcinoma had any evidence of recurrent disease after a mean postoperative follow-up of 32 months. Conclusions While the incidence of cancer at the time of surgery for IBD-related dysplasia is not negligible, the rate of node-positive disease is low.

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.

ABSTRACTIL‐17 inhibitors effectively treat psoriasis and psoriatic arthritis but may increase the risk of inflammatory bowel disease (IBD). We assessed their association with IBD compared to apremilast. Utilising the TriNetX database, we analysed patients with psoriasis or ankylosing spondylitis initiating IL‐17 inhibitors or apremilast. We used propensity score matching and Cox models to estimate IBD risk. Among 13,216 matched patients per group, 142 developed IBD with IL‐17 inhibitors versus 60 with apremilast (aHR = 2.50, 95% CI: 1.85–3.39). IL‐17 inhibitors increase IBD risk, necessitating careful patient selection and monitoring.

Abstract Objectives Oral extraintestinal manifestations (OEIMs) of inflammatory bowel disease (IBD) may impact IBD treatment. The aims of this study were to: (1) determine which OEIMs are most prevalent among patients with IBD, (2) investigate the presence of a temporal association between GI luminal disease activity and OEIMs, and (3) determine how often changes in therapeutic management of IBD are needed in the presence of OEIMs. Study Design A retrospective cohort study was performed for adult patients with IBD evaluated between January 2017 and November 2021 with at least 1 oral complaint. Demographic data were collected from the charts of these patients. Kruskal-Wallis test for continuous measures and Fisher’s Exact test for categorical measures were used. Results A total of 116 patients with IBD who had presented with at least 1 oral finding during the study time period were identified. Aphthous ulcers were the most common oral presentation in both Crohn’s disease (CD) (85.1%) and ulcerative colitis (UC) (75.0%). OEIMs were associated with CD activity in the small intestine (P = .004) and colon (P < .001). UC pancolitis was associated with OEIMs (P = .002). In 32.7% of patients, OEIMs led to either an increase in dose or frequency of IBD therapy. In an additional 16.4% of patients, new systemic agents were started because of the OEIMs. Conclusions This study provides evidence that patients with IBD may develop OEIMs synchronous with IBD flares and may require escalation of IBD therapy when OEIMs occur.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at an increased risk of infections. Before the COVID-19 pandemic, respiratory syncytial virus (RSV) followed predictable seasonal patterns, which have been recently disrupted. This study aimed to investigate whether severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) infection is associated with an increased risk of RSV infection in patients with IBD compared with those without a history of SARS-CoV-2 infection. METHODS: This retrospective cohort study used the TriNetX database to identify patients aged 18 years and older with IBD and SARS-CoV-2 infection (IBD-SARS-CoV-2 cohort) during the 2022 and 2023 RSV seasons. A 1:1 propensity score matching was used to compare patients with IBD but no history of SARS-CoV-2 infection (IBD non-SARS-CoV-2 cohort). RESULTS: In the 2022 IBD-SARS-CoV-2 cohort (mean age: 53.7 ± 17.6 years; 59% female; 77% White), the RSV infection risk was 0.47%, higher than 0.19% in the matched IBD non-SARS-CoV-2 cohort (adjusted odds ratio [aOR]: 2.4; 95% CI: 1.5–3.6). The risk was highest 30–60 days after SARS-CoV-2 infection (aOR: 2.9; 95% CI: 1.7–4.9), particularly in those aged 60 years and older (aOR: 2.5; 95% CI: 1.3–4.5). The use of systemic corticosteroids (aOR: 2.3; 95% CI: 1.1–4.6) or immune-modifying therapies (aOR: 3.9; 95% CI: 2–7.1) was associated with higher RSV infection risk. Similar trends were observed during the 2023 RSV season, with no significant differences in RSV-related hospitalizations. DISCUSSION: Adults with IBD have a higher risk of RSV infection after SARS-CoV-2 infection, particularly those receiving steroids or immune therapies. SARS-CoV-2 infection may have contributed to the recent RSV infection surge in this population, warranting further research.

INTRODUCTION: Immune-modifying therapies in pediatric inflammatory bowel disease (IBD) increase infection risks, including varicella. METHODS: Using Optum's deidentified Clinformatics Data Mart Database, a nationwide US commercial insurance claims database (2007–2022), we conducted a retrospective study of 5,368 patients with IBD aged 21 years or younger matched to a non-IBD cohort. The primary outcome was incidence of varicella. RESULTS: Varicella incidence was low in both groups (IBD: 0.570 vs non-IBD: 0.297 per 1,000 person-years, P = 0.23). At year 4, cumulative varicella incidence was 0.27% for IBD and 0.18% for non-IBD ( P = 0.24). No hospitalizations or deaths occurred. DISCUSSION: Despite immune-modifying therapy, pediatric patients with IBD demonstrate low varicella incidence.

Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn’s disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 years ago, their implementation in clinical practice remains suboptimal. Factors limiting the ‘real’ use of biosimilar anti-TNF-α medicines may include an ongoing lack of understanding and acceptance of biosimilars by both healthcare professionals (HCPs) and patients, as well as systemic factors such as formulary decisions outside of the control of the prescriber. In this review, an expert panel of gastroenterologists discusses HCP-level considerations to improve biosimilar anti-TNF-α utilization in IBD in order to support early anti-TNF-α initiation and maximize patient outcomes.

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 Background Iron deficiency is common in patients with inflammatory bowel disease (IBD), where poor absorption or prior surgery often renders oral iron supplementation ineffective, necessitating intravenous (IV) iron therapy. Hypophosphataemia, particularly associated with ferric carboxymaltose via fibroblast growth factor 23 dysregulation, is a recognized complication of IV iron therapy. It can result in severe outcomes such as rhabdomyolysis, osteomalacia, fractures, and convulsions. This study evaluates the risk of hypophosphataemia between ferric carboxymaltose and other IV iron formulations and its association with complications. Methods This retrospective propensity-matched study utilised the TriNetX database, a global repository of de-identified electronic health records. The first analysis compared ferric carboxymaltose to other IV iron formulations (iron sucrose, sodium ferric gluconate, ferumoxytol, ferric derisomaltose), matched on demographics (age, gender, ethnicity) and comorbidities (vitamin D deficiency, malnutrition, malabsorption, diabetes, CKD by stage, alcohol abuse, hyperparathyroidism, corticosteroid, diuretic, antacid, and bisphosphonate use) to assess hypophosphataemia risk. The second and third analyses evaluated hypophosphataemia-related complications in ferric carboxymaltose versus other formulations, both in the general population and in patients with IBD. Results We compared 115,242 ferric carboxymaltose patients to those on other IV iron formulations. Ferric carboxymaltose was associated with higher odds of severe (OR: 2.84, 2.22–3.64, p<0.0001) and moderate (OR: 1.37, 1.29–1.46, p<0.0001) hypophosphataemia but lower odds of mild hypophosphataemia (OR: 0.84, 0.79–0.88, p<0.0001). Among 25,586 hypophosphataemic patients, those on ferric carboxymaltose had lower odds of acute complications within 3 months, including muscle weakness (OR: 0.57, 0.47–0.70, p<0.0001), rhabdomyolysis (OR: 0.38, 0.20–0.75, p=0.003), disorientation (OR: 0.53, 0.46–0.61, p<0.0001), convulsions (OR: 0.59, 0.48–0.73, p<0.0001), cardiac arrhythmias (OR: 0.61, 0.54–0.69, p<0.0001), and respiratory failure (OR: 0.57, 0.50–0.64, p<0.0001). Over 2 years, chronic complications such as osteomalacia and fractures (23,508 patients each) showed no differences. In patients with IBD, no significant differences were observed in acute (2,688 each) or chronic complications (2,541 each) between cohorts. Conclusion Ferric carboxymaltose was linked to higher odds of severe and moderate hypophosphataemia but fewer acute complications than other IV iron formulations. The reasons for these differences remain unclear and warrant further research to understand the relationship between IV iron, hypophosphataemia, and clinical outcomes.

Abstract Objectives Patients with hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) experience a wide array of symptoms and system disorders. This study aimed to identify whether differences occurred in 115 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD. Methods In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions. Results From 1 November 2019 to 7 March 2024, the EDS Clinic saw 2088 patients. Using the 2017 diagnostic criteria, 66.5% were diagnosed with HSD (n = 1389), 20.3% with hEDS (n = 423), 10.6% with historic HSD (H-HSD) or localized HSD (L-HSD) (n = 256) (hypermobile controls) and 2.6% were not diagnosed with hEDS, HSD, H-HSD or L-HSD (n = 55) (controls). Symptoms/comorbidities that occurred with high prevalence in both hEDS and HSD included joint pain (hEDS 82.0%, HSD 88.9%), allergy (hEDS 77.0%, HSD 77.0%), subluxations (hEDS 71.2%, HSD 72.6%), brain fog (hEDS 70.0%, HSD 74.7%), headache (hEDS 68.1%, HSD 69.1%), anxiety (hEDS 60.3%, HSD 69.3%), depression (hEDS 52.2%, HSD 58.0%), migraine (hEDS 53.7%, HSD 52.5%), nausea (hEDS 54.6%, HSD 59.5%) and constipation (hEDS 53.0%, HSD 57.2%). In contrast, 9/115 (8%) symptoms/comorbidities were self-reported significantly more often in hEDS but 42/115 (37%) in HSD. hEDS patients reported more symptoms that suggest a defect in collagen, such as dislocation, hernias and rectal prolapse, while HSD patients reported more joint, muscle, allergy, neurological, gastrointestinal, sleep and psychological symptoms/comorbidities. Conclusion Although we found an overlap in some symptoms and comorbidities self-reported by hEDS/HSD patients, such as allergy/atopy, headache/migraine and gastrointestinal symptoms, our findings suggest key differences exist between the two diagnoses, suggesting that hEDS and HSD may be distinct conditions.