Faculty Bibliography

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: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.

INTRODUCTION/BACKGROUND:It is uncertain whether the risk of major congenital anomalies (mCAs) is increased in children of women with inflammatory bowel disease (IBD). METHODS:We aimed to determine the risk of mCAs in a Swedish nationwide cohort of 13,131 singleton live births from 1997 to 2020 to women with IBD and 61,909 matched children to women without IBD from the general population. We additionally examined mCAs according to periconceptional histological inflammation (vs remission: 1,124 and 646 births, respectively) or clinically active IBD (vs quiescent: 3,380 and 6,603 births, respectively). Adjusted risk ratios (aRRs) for overall and organ-specific mCAs were estimated using generalized linear models. These models adjusted for maternal sociodemographics, comorbidities, body mass index, and smoking. RESULTS:There were 38.0 (n = 499) mCAs per 1,000 births to women with IBD vs 33.9 (n = 2,101) in matched comparators and a risk difference of 1 extra mCA per 246 births to women with IBD (aRR 1.11; 95% confidence interval [CI] 1.01-1.23). Risks of heart defects and mCAs of the urinary system partly drove estimates. The risk of mCAs was similar in children of women with ulcerative colitis and Crohn's disease. Periconceptional histological inflammation (vs remission) or clinically active (vs quiescent) IBD did not further influence the risk of mCA in the child (aRR 0.87 [95% CI 0.55-1.40] and aRR 1.04 [95% CI 0.85-1.27], respectively). DISCUSSION/CONCLUSIONS:Children of women with IBD had a heightened susceptibility to mCAs, although absolute and relative risks were lower than previously reported. IBD activity was not linked to mCA risks, but those analyses included relatively few events.

BACKGROUND AND AIMS/OBJECTIVE:PredictSURE IBD is a prognostic blood test that classifies newly diagnosed, treatment-naïve Inflammatory Bowel Disease (IBD) patients into 'IBDhi' (high-risk) or 'IBDlo' (low-risk) groups (risk of future aggressive disease). We evaluated this assay in a multinational cohort and explored the effect of concomitant corticosteroids on its discrimination. METHODS:One hundred thirty-six (71 Ulcerative colitis [UC], 65 Crohn's Disease [CD]) and 41 (15 UC, 26 CD) patients with active IBD were 'unexposed' and 'exposed', respectively, to corticosteroids at baseline blood sampling. The number of treatment escalations, time to first escalation, and need for repeated escalations were compared between the biomarker subgroups. Another 20 patients (13 UC, 7 CD) were longitudinally sampled over 6 weeks after commencing corticosteroids. RESULTS:In corticosteroids-naïve UC and CD patients, all bowel surgeries (n = 6) and multiple therapy escalations (n = 10) occurred in IBDhi patients. IBDhi UC patients required significantly more treatment escalations, had a shorter time to first escalation, and a greater need for multiple escalations than IBDlo patients. No statistically significant differences were observed among CD patients. In corticosteroid-exposed patients, 66.6% of 'misclassifications' were IBDlo patients who required escalations. Among corticosteroid-treated patients with longitudinal sampling, 81.3% of those classified as IBDhi before steroids switched to IBDlo during therapy. CONCLUSIONS:No significant differences in treatment escalations were observed between biomarker-defined subgroups in CD. However, IBDhi UC patients required significantly earlier and more frequent therapy escalations, highlighting the need to further investigate PredictSURE IBD in UC. Notably, the discrimination ability of the biomarker was unreliable in patients receiving corticosteroid therapy.

INTRODUCTION/UNASSIGNED:In the general population, right I-sided dysplasia presents a higher risk for colorectal cancer (CRC) and metachronous dysplasia compared to left (L)-sided dysplasia. Given that patients with inflammatory bowel disease (IBD) are at higher risk for dysplasia than the general population, we sought to assess the risk factors as well as the differences in outcomes between patients with R-sided, L-sided, and both R- and L-sided dysplasia. METHODS/UNASSIGNED:A retrospective chart review was performed on patients at NYU Langone Health who had evidence of dysplasia on a colonoscopy between 2011 and 2021. Demographics and pertinent medical history were compiled. Cohorts were based on the dysplasia location (R-sided, L-sided, or R- and L-sided) and the IBD-related outcomes were analyzed. RESULTS/UNASSIGNED:= 0.03). CONCLUSIONS/UNASSIGNED:Patients with UC had a higher risk for L-sided colonic dysplasia compared to patients with CD; however, there were no differences in the progression of dysplasia between those who had R-sided and those who had L-sided dysplasia. Larger studies are needed to assess the risk factors and outcomes related to the laterality of dysplasia and further validate these findings among patients with IBD.

BACKGROUND:Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disorder of the gastrointestinal tract. In IBD, systemic inflammation and immune dysregulation may also impact extraintestinal organs, such as the thyroid gland. Despite this, little is known about the influence of concomitant hypothyroidism on the clinical course of IBD. METHODS:A retrospective analysis was conducted among adult patients with IBD and at least one thyroid stimulating hormone (TSH) measurement within a large healthcare network. Patient charts were reviewed, and baseline demographics, disease characteristics, biomarkers, healthcare utilization, medication use, and other comorbidities were extracted. Patients were stratified by those with IBD only and those with concomitant IBD and hypothyroidism. Multivariable logistic regression was used to identify factors associated with concomitant hypothyroidism. Concomitant disease as an independent predictor for lab abnormalities and increased healthcare utilization was also assessed using multivariable logistic and negative binomial regression. RESULTS:IRR: 1.89, 95% CI 1.08, 3.32). CONCLUSION/CONCLUSIONS:Patients with both IBD and hypothyroidism have an increased likelihood of other extraintestinal manifestations compared to individuals who have IBD without hypothyroidism. Furthermore, patients with concomitant disease exhibited greater healthcare utilization, specifically, increased rates of RBAI studies. The presence of concomitant hypothyroidism may be associated with a more severe course of IBD.

BACKGROUND AND AIMS/OBJECTIVE:In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies suggest that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared to unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue. METHODS:Since 2016, patients with IBD and confirmed index cancer prior to enrollment were followed annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within five years were excluded. Primary outcome was development of incident cancer related to exposure to immunosuppressive medications. RESULTS:Among 305 patients (47% male, 88% white), median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During median follow-up of 4.8 years, 210 (69%) were exposed to immunosuppressive therapy and 46 (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58/100 person-years versus 4.78/100 PY (relative risk 1.85, 95% CI 0.92-3.73) for immunosuppression exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and non-melanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, aHR, 1.41, 95% CI: 0.69-2.90), or with any major drug class. CONCLUSION/CONCLUSIONS:In this interim analysis of patients with IBD and a history of cancer, despite numerically elevated aHRs, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.

BACKGROUND:In patients with inflammatory bowel disease (IBD), multimorbidity with obesity and type 2 diabetes is common and increasing. Glucagon-like peptide 1 (GLP-1) receptor agonists are increasingly being prescribed for patients with IBD, yet their impact on patients with IBD is largely unknown. We aimed to assess the impact of GLP-1 receptor agonists on the course of IBD. METHODS:We identified all IBD patients prescribed GLP-1 receptor agonists at a large academic healthcare network between 2009 and 2023. We analyzed demographics and IBD characteristics in the year pre- and post-GLP-1 receptor agonist prescription and matched them to non-IBD controls. Our primary outcome was IBD exacerbation in the year following GLP-1 receptor agonist initiation, measured as a composite of IBD-related hospitalization, corticosteroid prescription, medication escalation or changes, or IBD-related surgery. Secondary outcomes included change in metabolic risk factors. RESULTS:Overall, 224 patients met inclusion criteria. At GLP-1 receptor agonist initiation, the median age was 54 years, 63% were female, 77% were White, and median BMI was 33.2 kg/m2. Compared to the 12-month period prior to GLP-1 receptor agonist initiation, in the 12 months post-GLP-1 receptor agonist initiation, there was no change in rates of IBD exacerbation, IBD-related hospitalization, steroids prescription, medication escalation or changes, or IBD-related surgery. There was a significant decrease in BMI in the year following GLP-1 receptor agonist initiation (median BMI 33.5 vs 31.6 kg/m2, P < .01), with rates of decrease comparable to non-IBD matched controls. CONCLUSIONS:In patients with IBD, GLP-1 receptor agonists are effective for weight loss and associated with few episodes of disease exacerbation.