Efficacy of Vedolizumab for Refractory Pouchitis of the Ileo-anal Pouch: Results From a Multicenter US Cohort.

BACKGROUND AND AIMS: Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn's disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis. METHODS: This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30. RESULTS: Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7-2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors. CONCLUSIONS: Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch.

Smoking Interacts With CHRNA5, a Nicotinic Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD-Related Surgery.

Background: Inflammatory bowel disease (IBD) is a chronic luminal disease with genetic and environmental factors affecting phenotype. This study evaluated the relationship between CHRNA5, a nicotinic receptor subunit gene, and smoking in predicting IBD-related surgery as well as the relationship between CHRNA5 and nicotine dependence. Methods: Participants completed a smoking questionnaire and were genotyped for CHRNA5 rs16969968. Demographic and clinical data were obtained from medical records. Wilcoxon, ANOVA, Chi square, and Fisher's exact tests were used for comparisons. Logistic regression was used to evaluate the effect of clinical and genetic predictors on surgery, stratified by disease subtype given paradoxical effects of smoking. Kaplan-Meier curves were used to examine the effect of smoking and genotype on time to surgery. (Significance: P < 0.05 for main effects; P < 0.2 for interaction terms). Results: 400 (65.8%) patients had Crohn's disease (CD) and 208 (34.2%) had ulcerative colitis (UC). 298 (49%) underwent an IBD-related surgery. There was a trend towards significance between rs16969968 and smoking behavior (smoking status [P = 0.05], nicotine dependence [AA > AG > GG; P = 0.08]). Smoking and genotype were not independently associated with surgery in UC or CD. However, interaction between rs16969968 and smoking in predicting surgery was observed for both UC (OR = 2.72; P = 0.05) and CD (OR = 2.88; P = 0.1). CHRNA5 genotype, but not smoking, predicted time to surgery in patients with UC (P = 0.007) but not in patients with CD. The interaction between smoking and genotype was not significantly associated with time to surgery in UC or CD. Conclusions: The CHRNA5 rs16969968 A variant interacts with smoking to influence IBD-related surgery. 10.1093/ibd/izx094_video1izx094.video15775248538001.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice.

BACKGROUND AND AIMS: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4ß7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. METHODS: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. RESULTS: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. CONCLUSIONS: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort.

Obesity is Associated With Poor Surgical Outcome in Crohn's Disease.

BACKGROUND: Published data suggest a link between obesity and adverse outcomes in Crohn's disease (CD). We aimed to test the hypothesis that obese CD patients would be more likely than non-obese CD patients to have poor surgical outcome when undergoing surgery for a complication of CD. METHODS: We designed a retrospective cohort study to test our hypothesis. The population comprised of adult CD patients who underwent CD related surgery at a tertiary referral center. The exposed and unexposed cohorts were represented by patients who were obese vs. non-obese at the pre-op visit respectively. Outcome was represented by successful vs. unsuccessful surgical outcome as deemed by the treating clinician. RESULTS: Ninety CD patients were eligible for inclusion into this cohort study of which 36 were obese (exposed cohort) and 54 were non-obese (unexposed cohort). Among obese CD patients, 64% had an unsuccessful surgical outcome vs. 41% with unsuccessful surgical outcome among the non-obese. Based on unadjusted bivariate analysis, potential confounders identified included age and type of surgery. Gender distribution, disease duration, ethnicity, tobacco use, steroid use, traditional and biological immune modulator use and clinical disease activity were similar between the two groups. Logistic regression adjusted for age and type of surgery revealed that obese CD patients were approximately 2.5 times more likely to have a poor surgical outcome than patients with CD who were not obese (P = 0.05 OR 2.53 95% CI 0.99 - 6.52). BMI as a continuous variable (adjusted for age and type of surgery) appeared to be associated with poor surgical outcome (P = 0.06 OR 1.07 95% CI 0.99 - 1.15). CONCLUSIONS: Obesity may be associated with poor surgical outcome in CD patients.

Clinical experience of natalizumab in Crohn's disease patients in a restricted distribution program.

BACKGROUND: Natalizumab (NAT) is a humanized monoclonal antibody against a4-integrin initially approved for the treatment of multiple sclerosis, and then withdrawn from the market in 2005 due to the risk of progressive multifocal leukoencephalopathy. NAT was approved for the treatment of Crohn's disease in the United States in 2008 under a restricted distribution program. There has been limited data on NAT since then. The purpose of this study was to review the experience with NAT in Crohn's disease patients at a tertiary inflammatory bowel disease center. METHODS: A retrospective chart review was performed on all patients who received NAT for treatment of refractory Crohn's disease from January 2008 to August 2010 at Washington University Medical Center in St. Louis. RESULTS: A total of 20 patients were identified and included in our study. Four patients did not complete induction therapy. Seven patients had a clinical response, with 5 patients continuing treatment up to 2012. Four patients had a partial response, 3 had adverse events, and 2 experienced loss of response. Two patients were pregnant while on NAT, and neither had significant adverse pregnancy outcomes. One patient dependent on total parenteral nutrition developed recurrent line sepsis while on NAT. Of the 5 patients on long-term maintenance therapy, 4 have a positive anti-JC virus antibody. No patients developed progressive multifocal leukoencephalopathy or other neurological complications. CONCLUSION: NAT remains a valuable alternative treatment option for patients with refractory Crohn's disease under a restricted distribution program.