Faculty Bibliography

BACKGROUND:Individuals with inflammatory bowel disease (IBD) have an elevated risk of colorectal neoplasia (CRN), including colorectal dysplasia and cancer (CRC). Despite surveillance strategies to prevent CRC, the clinical course of dysplasia types remains poorly understood. METHODS:We conducted a nationwide cohort study using the Swedish Patient Register and the ESPRESSO histopathology cohort to identify patients diagnosed with IBD between 1969 and 2023. Patients were classified according to their first (baseline) incident episode of dysplasia (no dysplasia, ND; indefinite, IND; low-grade, LGD; high-grade, HGD). Our primary outcome was future advanced CRN (HGD or CRC) during follow-up. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) were estimated using Cox regression. RESULTS:We identified 54,534 patients with IBD, including 1,320 with a first (baseline) episode of dysplasia (264 IND, 1031 LGD, 25 HGD), and 53,214 with ND. Over a median follow-up of 13.3 years, 2.3% of ND patients had future advanced CRN compared to 5.3% of IND patients (aHR 1.85, 95% CI 1.09-3.15) and 8.3% of LGD patients (aHR 3.51, 95% CI 2.77-4.45). Of those with HGD, 40% developed CRC (aHR 47.88, 95% CI 25.53-89.80). Risk factors for future dysplasia included male sex, younger age at diagnosis, extensive colitis, primary sclerosing cholangitis, and histologic inflammation. CONCLUSION/CONCLUSIONS:Patients with IBD and dysplasia have a significantly increased risk of future dysplasia, particularly among patients with HGD. Personalized surveillance strategies based on risk factors are critical for preventing advanced CRN.

BACKGROUND:Cognitive impairment, a precursor to dementia, is an important geriatric syndrome. We aimed to describe cognitive function in adults ≥60 years with inflammatory bowel disease (IBD) and determine the relationship between cognitive function and IBD activity. METHODS:We recruited IBD patients ≥60 years from 6 American centers. We collected demographics, IBD history, administered IBD activity indices and the Montreal Cognitive Assessment (MoCA). Follow-up assessments were nested in routine clinical care within one year. The primary outcome was change in cognitive function testing at follow-up; secondary outcome was IBD activity at follow-up. We constructed multi-variate logistic regression models to assess for the outcomes. RESULTS:We recruited 356 patients with a median age of 70 years (range: 60-89 years), 51% female, 66% had at least a Bachelor's degree; median IBD duration was 18 years and 60% had Crohn's disease. At baseline, 42% screened positive for cognitive impairment. Deficits in delayed recall and visuospatial functioning were the most prevalent. At follow-up within a year, 31% demonstrated an improved MoCA score, while 19% had a worse MoCA score. Adjusting for age, race, education, depression, number of comorbidities, IBD type, IBD duration as well as cognitive function score at baseline, symptomatically active IBD at baseline was significantly associated with worsening cognitive testing at follow-up (aOR:3.01, 95%CI:1.20-7.50). We also found that deficits in delayed recall, a MoCA sub-domain, were significantly associated with symptomatically active IBD at follow-up (aOR:2.22, 95%CI:1.10-4.47). CONCLUSION/CONCLUSIONS:These data provide further impetus to effectively treat IBD in older adults and suggest that delayed recall could be a useful screening tool for older adults with IBD.

INTRODUCTION/BACKGROUND:Potassium competitive acid blockers (PCABs) are superior to proton pump inhibitors (PPIs) for healing of Los Angeles (LA) class C/D erosive esophagitis (EE) and are approved for non-erosive gastroesophageal reflux disease (GERD) given their efficacy measured by heartburn-free days. However, they are more expensive than PPIs. We estimated the cost-effectiveness of PCABs compared to PPIs for the management of GERD. METHODS:A decision tree was constructed for the base case of a patient with GERD. We tested scenarios in which NERD, LA A/B, or LA C/D esophagitis was present, comparing PCABs to PPIs as first-line therapy, including step up therapy and/or class switching if symptoms persisted. Using publicly available cost estimates, quality-adjusted life years (QALYs) were compared using a willingness-to-pay (WTP) threshold of $100,000/QALY from a societal perspective at 6 months. RESULTS:The cost of PCABs for GERD was $3,240 more than PPIs, with an ICER of $144,208/QALY. When evaluating GERD phenotypes separately, the ICER was consistently over our WTP threshold. One-way analyses showed the most influential parameters were PCAB cost and efficacy for heartburn-free days. Probabilistic sensitivity analysis favored PPIs 71.7% out of 100,000 iterations. Reducing one-week costs to below $91 would make PCABs a cost effective first-line strategy across all GERD phenotypes. DISCUSSION/CONCLUSIONS:Despite PCAB efficacy, PPIs are a cost-effective strategy for GERD treatment, and can be positioned ahead of PCAB escalation on this basis. Reducing PCAB costs or accepting a higher WTP threshold would influence this finding, though PCABs may be favored in some current situations as evidenced by probabilistic sensitivity results.

BACKGROUND:Patients with inflammatory bowel disease (IBD) experience increased rates of sexual dysfunction (SD). This study investigated SD longitudinally in patients initiating a biologic or small molecule therapy. METHODS:Patients with Crohn's disease (CD) or ulcerative colitis (UC) starting biologic or small molecule therapy were surveyed at induction, 2 months, and 6 months. Measures included the IBD-Female and Male Sexual Dysfunction Scales (FSDS, MSDS), PROMIS Sexual Function and Satisfaction Brief Profile, Harvey Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI), partial Mayo score, Short IBD Questionnaire (SIBDQ), PHQ-9, and IBD Disability Index (IBDDI). Endoscopic and biomarker data were collected. Correlations, longitudinal changes, and predictors of SD were analyzed. RESULTS:A total of 170 patients (89 males, 81 females) completed baseline surveys, 132 at 2 months, and 115 at 6 months. Median age was 31.5 years; 59% had CD. At baseline, median HBI was 5.5, SCCAI 6, and pMayo 4. SD scores correlated with clinical disease activity (p < 0.05) but not consistently with endoscopic or biomarker measures. SD was associated with impaired quality of life, depression, and disability (p < 0.05). Among responders to therapy, SD, SIBDQ, and IBDDI significantly improved (p < 0.05). Multivariate analysis showed that more severe clinical disease activity predicted worse SD, while time after therapy initiation and improved quality of life were independently associated with better SD. CONCLUSIONS:Advanced therapy can improve SD in IBD. Improvements appear to be mediated by reductions in clinical disease activity and psychosocial factors.

PURPOSE OF REVIEW/UNASSIGNED:Dysphagia is a common medical condition among the geriatric population that can significantly impact a patient's quality of life. The manifestations, diagnosis, and treatment of esophageal dysphagia differ greatly based on the underlying etiology, especially in older individuals who may have accompanying complex medical comorbidities. This review explores the intricacies of esophageal dysphagia in the older population and how they are managed. RECENT FINDINGS/UNASSIGNED:Novel modalities, like the functional luminal imaging probe (FLIP) and timed barium esophagram (TBE), are now woven into our diagnostic schemas for esophageal dysphagia. Studies have also looked at the safety profile of available therapeutic interventions for older individuals. There are newer, less invasive treatment options, including radiofrequency application (RFA) and transoral incisionless fundoplication (TIF) for GERD management, that may benefit the geriatric population. SUMMARY/UNASSIGNED:In this review, we discuss the most likely etiologies of esophageal dysphagia in the elderly population. We then explore a diagnostic schema and highlight treatment choices based on diagnosis. Our review specifically explores the risks and benefits of management options in more medically complex geriatric patients.

INTRODUCTION/BACKGROUND: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/CONCLUSIONS: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.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Beyond genetics, environmental factors may contribute to the rising incidence of inflammatory bowel disease (IBD). Statins, widely used for cardiovascular risk reduction, also have anti-inflammatory properties and have been hypothesized to reduce IBD risk, though data are limited. We prospectively assessed the association between statin use and risk of developing IBD among individuals eligible for statin therapy for primary prevention of cardiovascular disease. METHODS:Using a prospective new user design within the Danish National Registries, we identified a nationwide cohort of individuals aged ≥40 years from 2008 to 2022 eligible for statin therapy for primary cardiovascular prevention. Statin users were matched 1:5 to nonusers on age, sex, calendar year, and cardiovascular risk factors. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for incident IBD. RESULTS:We identified 110,961 statin users and 554,805 matched nonusers. Statin use was associated with a reduced risk of IBD (aHR 0.84, 95% CI 0.72-0.97), with subgroup analyses showing similar reductions for Crohn's disease (aHR 0.84, 95% CI 0.65-1.09) and ulcerative colitis (aHR 0.83, 95% CI 0.69-1.00). This corresponds to a number needed to treat of 2881 to prevent one additional IBD case over 5 years of statin treatment. Findings remained consistent when censoring individuals at statin discontinuation. CONCLUSION/CONCLUSIONS:In this nationwide prospective study, statin use among individuals eligible for primary cardiovascular prevention was associated with a lower risk of developing IBD. These findings suggest a potential additional benefit of statins and support further research into their role in IBD prevention.

BACKGROUND:Older adults with ulcerative colitis (UC) have unique treatment challenges. Ozanimod is approved for the treatment of moderately to severely active UC in adults based on the phase 3 True North (TN) study results. Here, we analyzed the impact of patient age on ozanimod safety and efficacy in TN and during the open-label extension (OLE). METHODS:Patients were stratified by age at TN baseline: <40, 40 to 60, and >60 years (cutoff: 75 years). Safety was evaluated in all patients during TN and the OLE; efficacy was assessed at weeks 10 and 52 in TN and up to OLE week 190 in patients who entered as TN week 52 ozanimod clinical responders. RESULTS:Of 1012 patients analyzed, 492 were <40 years of age, 404 were 40 to 60 years of age, and 116 were >60 years of age. Infection, malignancy, cardiac events, and macular edema were low throughout TN across all ages. Exposure-adjusted incidence rates (EAIRs) of opportunistic and serious infections increased with age during the OLE. Patients ≥40 years of age had higher hypertension EAIRs than those <40 years of age, but EAIRs of other cardiovascular TEAEs were low. No cases of progressive multifocal leukoencephalopathy occurred over 242 weeks of ozanimod exposure. Efficacy rates for evaluated clinical and mucosal endpoints at weeks 10 and 52 with ozanimod were generally consistent across age groups with the overall population; similar trends were observed in the OLE. CONCLUSIONS:Ozanimod safety was similar and efficacy was generally comparable across age groups, although statistical significance vs placebo was not achieved in patients >60 years of age.

BACKGROUND:Infliximab (IFX) is commonly used in the management of acute severe ulcerative colitis (ASUC), yet up to 30% of individuals still require colectomy within 1 year. Clinical data characterizing these patients, however, are limited. AIMS/OBJECTIVE:We aimed to determine risk factors for colectomy among patients with ASUC who received in-hospital IFX treatment. METHODS:We performed a retrospective analysis of patients with ASUC who were treated with at least one dose of IFX while admitted between 2014 and 2022. Cox proportional hazards (PH) models were used to assess demographic, clinical, and laboratory risk factors for colectomy within 30 days and 1 year of IFX initiation. RESULTS:Overall, 36/170 (21.2%) patients underwent colectomy within 1 year of IFX initiation, with 22 (12.9%) individuals requiring colectomy within 30 days. On univariable analysis, concomitant Clostridioides difficile infection during admission, a ≤50% decrease in C-reactive protein (CRP) and experiencing 3 or more bowel movements per day within 48 hours after an initial IFX dose were significantly associated with 1-year colectomy. On multivariable Cox PH analysis, C. difficile infection during admission (aHR=2.92, 95% CI: 1.12-7.58) and a higher CRP/albumin ratio on admission (aHR=1.13, 95% CI: 1.01-1.27) were associated with increased colectomy risk within 1 year of IFX initiation. CONCLUSIONS:C. difficile infection and a higher CRP/albumin ratio on admission are associated with decreased time to colectomy within 1 year of IFX among patients presenting with ASUC. These factors may aid in early risk stratification to minimize delays in JAK-inhibitor initiation or surgical referral.