Faculty Bibliography

BACKGROUND:Chronic intestinal inflammation is a well-established driver of colorectal dysplasia in inflammatory bowel disease (IBD). However, the role of metabolic factors such as obesity remains poorly understood. We evaluated whether chronic obesity, measured using five-year longitudinal body mass index (BMI), is independently associated with colorectal dysplasia in patients with IBD. METHODS:using all outpatient measurements over a five-year period prior to the index colonoscopy. Multivariable conditional logistic regression was used to evaluate the association between obesity and dysplasia, adjusting for established dysplasia risk factors and surveillance-related variables. RESULTS:A total of 312 patients were included (156 dysplasia cases and 156 matched controls). Dysplasia cases had significantly longer IBD duration compared with controls (median 12.1 vs. 8.0 years, p < 0.01) and were more likely to have a history of prior colorectal dysplasia (16.0% vs. 3.8%, p < 0.01). In multivariable analysis, obesity was independently associated with colorectal dysplasia (adjusted odds ratio [aOR] 2.23, 95% CI 1.08-4.57). Longer disease duration (aOR 1.05 per year, 95% CI 1.02-1.08) and prior dysplasia (aOR 4.88, 95% CI 1.69-14.06) were also independently associated with dysplasia. In a secondary model adjusting for additional surveillance-related and structural colonic factors, obesity remained significantly associated with dysplasia (aOR 2.11, 95% CI 1.05-4.24). CONCLUSIONS:Obesity is independently associated with colorectal dysplasia in patients with IBD, suggesting that metabolic factors contribute to neoplastic risk beyond traditional inflammation-driven pathways. Incorporation of metabolic risk into dysplasia risk stratification may improve CRC prevention strategies in IBD.

GOAL/OBJECTIVE:To investigate the safety of corticosteroid escalation before antimicrobial treatment among inflammatory bowel disease (IBD) flares associated with an enteric infection. BACKGROUND:Corticosteroids are often necessary to treat individuals with IBD; however, there is concern that immunosuppression in the setting of a gastrointestinal infection may worsen outcomes. METHODS:We conducted a retrospective study of adults (18 y or older) hospitalized for an IBD flare (2015 to 2023) who received both systemic corticosteroids and antimicrobials for a gastrointestinal infection. The primary outcome was a composite of in-hospital death, IBD-related surgery, need for intensive care unit, toxic megacolon, or acute kidney injury, stratified by timing of corticosteroid escalation (before vs. after antimicrobial initiation). Outcomes at 90 days were also collected in a secondary analysis. RESULTS:Overall, 76 individuals were included; 48 (63.2%) had ulcerative colitis. The most common infection was Clostridioides difficile (n=50; 65.8%), and the majority of patients (n=51, 67.1%) received corticosteroid initiation (or escalation) before antimicrobials. There was no significant difference in the development of the primary (9.8% vs. 8.0%, P=1.00) or secondary (29.4% vs. 32.0%, P=0.82) outcome based on corticosteroid initiation before versus after antimicrobial initiation. Among patients with C. difficile, similar results were seen. CONCLUSIONS:Among patients hospitalized with an IBD flare complicated by enteric infection, initiation or escalation of corticosteroids before antimicrobial therapy did not increase the risk of in-hospital or 90-day adverse events. This study supports the notion that corticosteroids can be safely utilized while awaiting the results of the gastrointestinal infectious testing.

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:The benefits of achieving endoscopic remission among older adults with inflammatory bowel disease (IBD) who have mild persistent disease activity are unknown. METHODS:This was a retrospective study of adults ≥ 60 with IBD who had mild or no disease activity on endoscopy from January 1, 2018-January 1, 2023. The primary outcome was a composite of major IBD-specific adverse events (hospitalizations, surgery, and prescription of corticosteroids for IBD-related symptoms) within 1 year of endoscopic assessment. Our secondary outcome was a composite of 1-year morbidity-related events (mortality, all-cause hospitalization, infection requiring antibiotics, venous thromboembolism, cardiovascular events, and osteoporotic fractures). We also assessed outcomes at 5 years. RESULTS:Among 504 patients, 192 (38.1%) had mild endoscopic disease and 312 (61.9%) were in endoscopic remission, with a median disease duration of 11 years. On multivariable analysis, mild endoscopic disease activity increased the odds of a 1-year adverse IBD-specific outcome (aOR 4.16, 95% CI 2.10-8.24), with similar results at 5 years. Furthermore, mild endoscopic disease was associated with increased odds of experiencing an adverse morbidity-related outcome within 1 year as compared to endoscopic remission (aOR 1.56, 95% CI 1.01-2.43). CONCLUSIONS:Among older adults with prevalent IBD, mild endoscopic disease activity, as compared to endoscopic remission, was associated with increased odds of adverse IBD-specific and morbidity-related outcomes at 1 year, with this risk persisting for IBD-specific outcomes at 5 years. These findings highlight the importance of achieving endoscopic remission, which may confer both short- and longer-term benefits in this population.

BACKGROUND:Surgery in select individuals with inflammatory bowel disease (IBD) may obviate the need for future IBD-related treatment. AIMS/OBJECTIVE:To characterise individuals who remain treatment-free during the first 5 years after initial IBD-related surgery. METHODS:We performed a nationwide cohort study using the Swedish National Patient Register and the ESPRESSO histopathology to identify individuals undergoing first IBD-related intestinal resection for Crohn's disease (CD) or total colectomy for ulcerative colitis (UC) between 2007 and 2018. We calculated adjusted odds ratios (aORs) for the need for any IBD-related therapy within the first 5 years post surgery. RESULTS:We included 1709 individuals with CD and 1010 with UC. At 5 years, 21.5% with CD and 42.4% with UC remained 'treatment free'. Being 'treatment free' 5 years after surgery was more common among patients with CD who had longer preoperative disease duration and older adults with UC. It was less common among individuals with extraintestinal manifestations of disease (CD aOR 0.64, 95% CI 0.43-0.97; UC aOR 0.48, 95% CI 0.31-0.73) and patients with CD who had chronic obstructive pulmonary disease. CONCLUSIONS:Surgery obviated the need for future therapy in 22% of patients with CD and 42% with UC. Absence of extraintestinal manifestations, older age in UC, and longer disease duration and absence of chronic obstructive pulmonary disease in CD may highlight an opportunity for precision surgery to identify those most likely to achieve long-term benefit from surgical intervention.

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.

PURPOSE/OBJECTIVE:There is a lack of safety and efficacy data for newer biologic agents among adults ≥ 60 years old with inflammatory bowel disease (IBD) given their limited inclusion in clinical trials. We conducted a retrospective cohort study comparing the safety and efficacy of ustekinumab (UST) or vedolizumab (VDZ) use in older adults as compared to younger adults with IBD. METHODS:This single-center retrospective study compared individuals 18 to 59 years old to individuals ≥ 60 years old with a confirmed diagnosis of IBD who began VDZ or UST treatment between 2014 and 2022. The primary efficacy and safety outcomes were endoscopic remission and serious infection, respectively. Secondary outcomes included endoscopic response, clinical remission, and non-severe adverse events. Multivariable regression was used to identify factors independently associated with safety and efficacy. RESULTS:Overall, 948 individuals were included, with 779 (82.2%) < 60 years-old. In total, 548 (57.8%) had Crohn's disease, 367 (38.7%) had ulcerative colitis, 33 (3.5%) had indeterminate colitis, and a total of 403 individuals (42.5%) initiated VDZ whereas 545 (57.5%) initiated UST. When assessing efficacy, younger and older individuals had comparable rates of endoscopic remission (< 60 years-old 27.5% vs 29.0% ≥ 60 years-old, p = 0.69) as well as clinical remission (< 60 years-old 26.4% vs 26.6% ≥ 60 years-old, p = 0.96). When assessing safety, serious infection rates (< 60 years-old 8.9% vs 8.9% ≥ 60 years-old, p  = 0.99) and non-severe adverse event rates (< 60 years-old 12.3% vs 8.9% ≥ 60 years-old, p = 0.21) were not significantly different. On multivariable analysis, measures of disease severity (prior advanced therapy use, prior corticosteroid use, severe disease) significantly decreased the odds of endoscopic and clinical remission. Additionally, prior advanced therapy use and the presence of comorbidities increased the odds of serious infections. CONCLUSION/CONCLUSIONS:The use of UST and VDZ had similar efficacy and safety outcomes in older adults as compared to younger individuals with IBD. Decisions to utilize these biologics should be driven by overall disease burden and comorbidities, and not be deferred due to advanced chronological age alone.