Bharati Kochar

Depression Is Associated With More Aggressive Inflammatory Bowel Disease

Objectives:Depression is prevalent in inflammatory bowel disease (IBD) patients. The impact of depression on IBD is not well-studied. It is unknown how providers should assess depression.Methods:We used data from the Sinai–Helmsley Alliance for Research Excellence cohort, to assess methods of diagnosing depression and effects of baseline depression on disease activity at follow-up. A patient health questionnaire (PHQ-8) score ≥5 was consistent with mild depression. Relapse was defined as a modified Harvey–Bradshaw Index ≥5 or Simple Clinical Colitis Activity Index >2. We performed binomial regression to calculate adjusted risk ratios (RRs).Results:We included 2,798 Crohn’s disease (CD) patients with 22-month mean follow-up and 1,516 ulcerative colitis (UC) patients with 24-month mean follow-up. A total of 64% of CD patients and 45% of UC patients were in remission at baseline. By self-report, 20% of CD and 14% of UC patients were depressed. By PHQ-8, 38% of CD and 32% of UC patients were depressed (P<0.01). Adjusted for sex, remission, and disease activity, CD patients with baseline depression were at an increased risk for relapse (RR: 2.3; 95% confidence interval (CI): 1.9–2.8), surgery, or hospitalization (RR: 1.3 95% CI: 1.1–1.6) at follow-up. UC patients with baseline depression were also at increased risk for relapse (RR: 1.3; 95% CI: 0.9–1.7), surgery, or hospitalization (RR: 1.3; 95% CI: 1.1–1.5) at follow-up.Conclusions:Baseline depression is associated with a higher risk for aggressive IBD at follow-up. A single question is not a sensitive method of assessing depression. Providers should consider administering the PHQ-8 to capture those at greater risk for aggressive disease.

Diminishing Effectiveness of Long-Term Maintenance Topical Steroid Therapy in PPI Non-Responsive Eosinophilic Esophagitis

OBJECTIVES: While topical corticosteroids are first‐line therapy for eosinophilic esophagitis (EoE), the data regarding long‐term effectiveness are lacking. We aimed to determine long‐term histologic and endoscopic outcomes of maintenance therapy in EoE steroid responders. METHODS: We performed a retrospective study of adults with EoE at UNC Hospitals who had initial histologic response (<15 eos/hpf) after 8 weeks of topical steroids, and maintained on therapy. Endoscopic and the histologic data were recorded at baseline and follow‐up endoscopies. Multivariable logistic regression was performed to assess loss of treatment response by steroid dose at recurrence, and Kaplan–Meier analysis to calculate durability of disease remission. RESULTS: Of 55 EoE patients with initial response to swallowed/topical fluticasone or budesonide over a median 11.7 months, 33 had at least two follow‐up EGDs. Of these patients, 61% had histologic loss of response and worse endoscopic findings. There was no difference in baseline steroid dose (P=0.55) between the groups, but those maintained on their initial dose had lower odds (OR: 0.10; 95% CI: 0.01, 0.90) of loss of response compared to those who had subsequent dose reduction. On survival analysis, 50% had loss of response to steroids by 18.5 months and 75% by 29.6 months. CONCLUSIONS: In adult EoE steroid responders, loss of treatment response is common, and is associated with a steroid dose reduction. Routinely lowering doses for maintenance steroids may provide inferior outcomes.

Molecular classification of Crohn's disease reveals two clinically relevant subtypes

Objective The clinical presentation and course of Crohns disease (CD) is highly variable. We sought to better understand the cellular and molecular mechanisms that guide this heterogeneity, and characterise the cellular processes associated with disease phenotypes. Design We examined both gene expression and gene regulation (chromatin accessibility) in non-inflamed colon tissue from a cohort of adult patients with CD and control patients. To support the generality of our findings, we analysed previously published expression data from a large cohort of treatment-naïve paediatric CD and control ileum. Results We found that adult patients with CD clearly segregated into two classes based on colon tissue gene expression—one that largely resembled the normal colon and one where certain genes showed expression patterns normally specific to the ileum. These classes were supported by changes in gene regulatory profiles observed at the level of chromatin accessibility, reflective of a fundamental shift in underlying molecular phenotypes. Furthermore, gene expression from the ilea of a treatment-naïve cohort of paediatric patients with CD could be similarly subdivided into colon-like and ileum-like classes. Finally, expression patterns within these CD subclasses highlight large-scale differences in the immune response and aspects of cellular metabolism, and were associated with multiple clinical phenotypes describing disease behaviour, including rectal disease and need for colectomy. Conclusions Our results strongly suggest that these molecular signatures define two clinically relevant forms of CD irrespective of tissue sampling location, patient age or treatment status.

Modifiable Risk Factors for Hospital Readmission Among Patients with Inflammatory Bowel Disease in a Nationwide Database

Background: Previous studies suggest that disease activity alone does not reliably predict hospital readmission among patients with inflammatory bowel diseases (IBDs). Using a national database, we aimed to further describe the burden of readmissions for IBD and identify modifiable risk factors. Methods: We performed a retrospective cohort study using 2013 data from the Nationwide Readmission Database (NRD). Using International Classification of Diseases, ninth Revision, Clinical Modification (ICD-9-CM) codes, we identified adult patients with discharge diagnoses of ulcerative colitis or Crohns disease and ascertained diagnoses of anxiety, depression, chronic pain, tobacco use, and other comorbidities during index admission. Logistic regression was used to estimate factors associated with hospital readmission. Results: Among 52,498 hospitalizations of patients with IBD (63% Crohns disease and 37% ulcerative colitis), 12,407 (24%) were readmitted within 90 days of the index hospitalization, resulting in roughly

Safety and Efficacy of Teduglutide (Gattex) in Patients With Crohn's Disease and Need for Parenteral Support Due to Short Bowel Syndrome-associated Intestinal Failure.

576 million in excess charges. In multivariable analysis of patients with Crohns disease, anxiety (odds ratio [OR] 1.31, 95% confidence interval [CI], 1.21–1.43), depression (OR 1.27, 95% CI, 1.07–1.50), chronic pain (OR 1.31, 95% CI, 1.18–1.46), and tobacco abuse (OR 1.13, 95% CI, 1.06–1.22) were associated with a significant increase in odds of readmission. Among patients with ulcerative colitis, anxiety (OR 1.28, 95% CI, 1.14–1.45), depression (OR 1.35, 95% CI, 1.07–1.70), and chronic pain (OR 1.44, 95% CI, 1.21–1.73) were associated with a significant increase in odds of readmission. Conclusions: Readmission occurs frequently in patients with IBD and is costly. Anxiety, depression, and chronic pain may represent targets for interventions to prevent 90-day hospital readmission in this population.

Inflammatory Bowel Disease is Similar in Patients with Older Onset and Younger Onset

Background: Teduglutide is a GLP-2 analogue indicated for treatment of adults with short bowel syndrome (SBS). Because of the rarity of SBS, real-world safety or efficacy data are not available in patients with Crohn’s disease (CD) and SBS treated with teduglutide. Aim: To evaluate teduglutide’s safety and efficacy in CD patients with SBS. Methods: We conducted a retrospective cohort study at 3 tertiary centers in the United States between 2012 and 2014. Demographic, clinical, and therapeutic data were retrieved from medical record systems. Results: Thirteen CD patients were included, 8 (62%) of whom were on concomitant immunosuppression. Median duration of teduglutide therapy was 365 days [interquartile range (IQR), 122 to 482 d] and 9/13 patients (69%) remain on therapy. At teduglutide initiation, 69% were on parenteral nutrition. At conclusion of follow-up, 1 patient was on parenteral nutrition. All patients were on intravenous fluids (IVF) before teduglutide; median IVF were 9000 mL/wk (IQR, 7000 to 14,000 mL/wk). IVF requirements decreased by a median of 3100 mL/wk (IQR, 2400 to 8400 mL/wk). Six patients (46%) ceased IVF. Adverse events attributed to teduglutide were obstructive symptoms (n=1), pancreatitis (n=1), asymptomatic lipase and amylase elevation (n=1), nausea (n=1), and abdominal pain (n=1). Catheter-related sepsis occurred in 4 patients. Conclusions: This is the first report evaluating the safety and efficacy of teduglutide in a cohort of CD patients with SBS requiring parenteral support. More of half the cohort was on concomitant immunosuppression. Teduglutide seemed to be safe and the majority of patients were weaned off parenteral support.

Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches.

Background: As the American population is aging, the number of older people with inflammatory bowel disease is increasing. We used clinical data from the Sinai-Helmsley Alliance for Research Excellence (SHARE), a prospective cohort, to examine disease and treatment differences in older adults. Methods: We performed a cross-sectional study assessing demographics and disease behavior by age at diagnosis with univariate, bivariate, and multivariate analyses. “Older-onset” patients were diagnosed after age 60, “younger-onset” patients were diagnosed before age 60 but are older than 60 years, and the remainder were “young.” Results: There were 91 older-onset, 389 younger-onset, and 3431 young patients with Crohns disease. Older-onset patients had more ileal (37%) and colonic (27%) disease compared with younger-onset and young patients. There were no differences in disease behavior, location, or surgeries between older-onset and young patients with Crohns disease within 5 years of diagnosis. Older-onset patients with inflammatory disease had a higher odds of being in remission. Young patients reported more anti–tumor necrosis factor and thiopurine use compared with younger-onset and older-onset patients (P < 0.01). There were 98 older-onset, 218 younger-onset, and 1702 young patients with ulcerative colitis. There were no differences in disease extent, activity index, or surgeries. Young patients with ulcerative colitis reported more anti–tumor necrosis factor use (26%) compared with younger-onset patients (17%, P < 0.01). Conclusions: Disease behavior or location was not different between younger and older adults with inflammatory bowel disease. Older patients were less likely to be treated with immunosuppression. If older patients have similar disease behavior, less frequent treatment with immunosuppressives may risk suboptimally controlled disease.

Evaluation of Gastrointestinal Patient Reported Outcomes Measurement Information System (GI-PROMIS) Symptom Scales in Subjects With Inflammatory Bowel Diseases

Eosinophilic esophagitis (EoE) is a chronic immune-mediated clinicopathologic disease. The prevalence of EoE is approximately 1/2000 persons, EoE is now the most common cause of food impactions, with healthcare expenditures approaching US

The Burden of Hospital Readmissions among Pediatric Patients with Inflammatory Bowel Disease

1 billion annually. This article will discuss challenges related to proton pump inhibitor responsive esophageal eosinophilia, including distinguishing this condition from EoE and understanding the mechanisms behind the PPI response. For EoE, we will review multiple ongoing debates about treatment and monitoring strategies, including selecting treatment outcomes, optimizing medication formulations, approaching the steroid-refractory patient, conducting dietary elimination, prescribing long-term maintenance therapy and performing esophageal dilation.

Achieving Synergy: Linking an Internet-Based Inflammatory Bowel Disease Cohort to a Community-Based Inception Cohort and Multicentered Cohort in Inflammatory Bowel Disease

Objectives:Patient reported outcomes (PROs) are important treatment endpoints in inflammatory bowel diseases (IBD). We evaluated the gastrointestinal (GI) PRO Measurement Information System (PROMIS) in IBD subjects.Methods:Crohn’s and Colitis Foundation of America’s Partners is an Internet-based cohort of IBD subjects. Participants complete surveys, including demographics, disease characteristics, PROMIS domains, disease activity (short Crohns disease activity index or simple clinical colitis activity index) and quality of life (QoL) indices. In a nested cross-sectional study, we used univariate and bivariate analyses to assess associations between 8 GI-PROMIS domains (reflux, swallowing, diarrhea, nausea, belly pain, gas, incontinence, and constipation) and QoL and disease activity indices.Results:The study included 2,378 Crohns Disease (CD) and 1,455 ulcerative colitis (UC) respondents with a median age of 41 years. Median disease duration was 11 years for CD subjects and 8 years for UC subjects; 57% of CD subjects and 42% of UC subjects were in remission. Among symptomatic CD subjects, those with active CD reported significantly worse symptoms on all 8 domains than those in remission. The same was observed for UC subjects with the exception of disrupted swallowing. IBD subjects with worse QoL reported significantly worse symptoms on all 8 domains compared to those with better QoL.Conclusions:In IBD subjects experiencing GI symptoms, GI-PROMIS domains were strongly associated with disease activity and QoL indices. GI-PROMIS holds potential as PRO measures in IBD and correlates with other validated indices in this population.