Safety and Efficacy of Vedolizumab Versus Tumor Necrosis Factor α Antagonists in an Elderly IBD Population: A Single Institution Retrospective Experience.

BACKGROUND: Vedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population. AIMS: Here, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD. METHODS: This retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes. RESULTS: 212 cases were identified-108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p < 0.001). CONCLUSIONS: In a cohort of IBD patients over age 60, vedolizumab showed no statistically significant differences in infection, hospitalization, or surgical intervention-free survival as compared to anti-TNF. Vedolizumab was discontinued less frequently than anti-TNF. Patients on vedolizumab had higher rates of endoscopic remission and response.

Inpatient Management of Inflammatory Bowel Disease-Related Complications.

Despite advances in therapeutic options, a sizeable proportion of patients with inflammatory bowel disease require hospitalization or surgery during their lifetime. While current treatment guidelines for the management of ulcerative colitis and Crohn's disease cover the spectrum of disease severity and behavior, management of acute complications of inflammatory bowel disease can present unique challenges that are not always addressed in these guidelines. In this review, the authors provide a comprehensive summary of the existing literature focused on management of patients hospitalized with complications of inflammatory bowel disease. Proposed management algorithms are provided to guide clinicians through common scenarios to determine the most appropriate interventions - escalation of medical therapies, non-surgical therapeutic interventions (drainage of intra-abdominal abscess or endoscopic balloon dilation) or surgery. Prevention of complications is proposed through a multi-disciplinary approach that involves surgeons, dieticians, radiologists, pathologists and infectious disease consultants.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Background: Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. Methods: We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Results: Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Conclusions: Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn's Disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder that may affect any part of gastrointestinal tract with extra-intestinal manifestations and associated immune dysregulation. To characterize heterogeneity in CD, we profiled single-cell transcriptomics of 170 samples from 65 CD patients and 18 non-inflammatory bowel disease (IBD) controls in both the terminal ileum (TI) and ascending colon (AC). Analysis of 202,359 cells identified a novel epithelial cell type in both TI and AC, featuring high expression of LCN2, NOS2, and DUOX2, and thus is named LND. LND cells, confirmed by high-resolution in-situ RNA imaging, were rarely found in non-IBD controls, but expanded significantly in active CD. Compared to other epithelial cells, genes defining LND cells were enriched in antimicrobial response and immunoregulation. Moreover, multiplexed protein imaging demonstrated that LND cell abundance was associated with immune infiltration. Cross-talk between LND and immune cells was explored by ligand-receptor interactions and further evidenced by their spatial colocalization. LND cells showed significant enrichment of expression specificity of IBD/CD susceptibility genes, revealing its role in immunopathogenesis of CD. Investigating lineage relationships of epithelial cells detected two LND cell subpopulations with different origins and developmental potential, early and late LND. The ratio of the late to early LND cells was related to anti-TNF response. These findings emphasize the pathogenic role of the specialized LND cell type in both Crohn's ileitis and Crohn's colitis and identify novel biomarkers associated with disease activity and treatment response.

Functional Medicine Approach to Patient Care Improves Sleep, Fatigue, and Quality of Life in Patients With Inflammatory Bowel Disease.

Background: A Functional Medicine program was developed at an inflammatory bowel disease (IBD) center with the goal of integrating strategies to address modifiable lifestyle factors and to complete a 6-week elimination diet under the direction of a trained Functional Medicine dietitian and Functional Medicine providers. Methods: From January 2019 to November 2019, patients with controlled, but persistent, symptoms from IBD were offered enrollment. Each of the 5 visits incorporated an educational session focused on nutrition followed by a session focusing on modifiable lifestyle factors. The patients were placed on a supervised 6-week elimination diet. At each visit, patients completed the SIBDQ (Short Inflammatory Bowel Disease Questionnaire), FSS (Fatigue Severity Scale), PSQI (The Pittsburgh Sleep Quality Index), and MSQ (Medical Symptoms Questionnaire). Statistical analysis was performed using the Wilcoxon matched pairs signed-rank test. Results: Nineteen patients enrolled (2 men: 1 ulcerative colitis [UC], 1 Crohn's disease [CD]; 17 women: 3 UC, 14 CD). 15 patients completed all modules. There was improvement in all patient-reported outcomes (PROs) (FSS, P < .001; PSQI, P < .001; SIBDQ, P < .001; MSQ, P < .001). Every patient who completed the last session demonstrated weight loss. Conclusions: The psychoemotional roots to immune disease states, particularly IBD, are complicated and often not addressed in traditional care. We are just beginning to understand the impact of nutrition, sleep, stress, movement, and relationships on IBD. In this cohort, utilizing Functional Medicine as an adjunct to traditional care resulted in improvement in all PROs.

Tofacitinib Adherence and Outcomes in Refractory Inflammatory Bowel Disease.

Background: Tofacitinib has been approved for moderate-to-severe ulcerative colitis and studied in Crohn's disease. Understanding medication adherence to oral medications in severe disease is essential. Methods: We retrospectively reviewed adherence and real-world outcomes of inflammatory bowel disease patients who initiated tofacitinib at a single care center. Adherence was measured by proportion of days covered. Results: Sixty-three patients were identified. All patients failed at least one prior biologic therapy. Mean proportion of days covered was 95.7% for ulcerative colitis and 93.1% for Crohn's disease. Significant clinical and endoscopic response was seen. Conclusion: Adherence was high in a cohort with highly refractory disease.

Gastroenterologist-Lead Management of Iron Deficiency Anemia in Inflammatory Bowel Disease Is Effective, Safe, and May Increase Quality of Life.

BACKGROUND: The effectiveness and safety of gastroenterologist (GI)-lead treatment of iron deficiency anemia (IDA) in inflammatory bowel disease (IBD) have not been well-studied. METHODS: A retrospective chart review of patients with IBD, IDA, and evidence of treatment with iron at a tertiary IBD center was conducted. RESULTS: In 351 patients, hemoglobin and quality of life scores increased significantly after treatment with iron. Twelve of 341 patients treated with intravenous iron had an adverse effect. Twenty-seven patients required a hematology referral. CONCLUSION: GIs should consider treating patients with IBD and IDA with intravenous iron as it is safe and effective.

Does Reverse Causality Underlie the Temporal Relationship Between Depression and Crohn's Disease?

BACKGROUND: Studies suggest that there is a temporal relationship between depression and Crohn's disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression-CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective-cognitive dimension of depression. METHODS: We studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective-cognitive index of depression. Crohn's disease status and the affective-cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data. RESULTS: The results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective-cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse. CONCLUSIONS: The hypothesis that an affective-cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.

Management of Pouchitis and Other Common Complications of the Pouch.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the preferred surgical treatment for refractory or complicated ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Pouchitis is the most common complication of this procedure and can occur in about 50% of patients. Treatment of pouchitis depends on the phenotype of disease. Pouchitis can be classified as acute, chronic/refractory, or secondary pouchitis, which includes pouchitis occurring due to Crohn's disease (CD). CD of the pouch is becoming an increasingly recognized problem, and management is challenging. This article reviews the literature and offers treatment recommendations regarding management of pouchitis and CD of the pouch.

The Gastroenterologist's Role in Management of Perianal Fistula.

Perianal fistula occurs frequently in the Crohn disease population. Therapy for fistulas has changed through the years from primarily surgical management to multidisciplinary management among gastroenterologists, radiologists, and surgeons. Gastroenterologists play a role in assisting with diagnosis through endoscopic ultrasound and assessment of luminal disease activity, providing medical therapy including biologic therapy and antibiotics, and coordinating the multidisciplinary care with surgical and radiologic colleagues.