Irritable bowel syndrome (IBS) is one of the most common gastrointestinal ailments among those seeking health care for gastrointestinal disorders. Despite its prevalence, IBS pathophysiology is still not completely understood. Continued elucidation of IBS etiological mechanisms will lead to a greater appreciation of possible therapeutic targets. In the past decade, there has been increasing focus on the possible connection between increased intestinal mucosal permeability, inflammation, and visceral hypersensitivity. Increased permeability in subsets of IBS patients has been observed and the possible mechanisms underlying this defect are just beginning to be understood. The objectives of this review are to summarize the role of the healthy intestinal epithelium as a barrier between the lumen and the rest of the body with a focus on tight junctions; to examine the lines of evidence that suggest that different triggers lead to increased intestinal mucosal permeability and disruption of tight junctions in IBS patients; and to explore how this increased permeability may elicit immune responses that affect afferent nerves, resulting in the pain associated with IBS.

Vedolizumab had increased efficacy over placebo in CD patients irrespective of TNF-α antagonist treatment history. Overall, rates of response and remission were numerically higher in patients receiving vedolizumab as a first biologic than in patients who had experienced TNF failure.

IntroductionThe efficacy and safety of vedolizumab, a gut-selective α4β7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18–80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials.MethodsSafety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years.ResultsAt baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn’s disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person–years) and adverse events leading to hospitalization (14.8 per 100 person–years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death.ConclusionsThe safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted.FundingMillennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0467-6) contains supplementary material, which is available to authorized users.

We developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness.

In this large real-world cohort we observed that VDZ was well tolerated and effective in achieving key clinical outcomes.

Summary Background Vedolizumab is a gut‐selective immunoglobulin G1 monoclonal antibody to α4β7 integrin for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined. Aim To assess pregnancy outcomes in females and partners of males who received vedolizumab. Methods All pregnancy data collected during the clinical programme (from 14 May 2007 to 27 June 2013) and in the post‐marketing setting (to 19 November 2015) were analysed. Results Across six studies, there were 27 pregnancies in female participants and 19 pregnancies in partners of male participants. Among 24 vedolizumab‐treated females (23 with CD/UC, one healthy volunteer), there were 11 live births, five elective terminations, four spontaneous abortions and four undocumented outcomes. A congenital corpus callosum agenesis anomaly was reported in one live birth from a healthy volunteer with extensive obstetric history exposed to single‐dose vedolizumab 79 days before estimated conception. Of 19 pregnancies in partners of male participants, there were 11 live births, two spontaneous abortions, three elective terminations and three undocumented outcomes. Post‐marketing reports recorded 81 pregnancies, resulting in four live births, 11 spontaneous abortions and 66 pregnancies that were on‐going or reported undocumented outcomes. Conclusions Initial analysis, limited by sample size and follow‐up, identified no new safety concerns for pregnancy outcomes in females directly or indirectly exposed to vedolizumab. However, vedolizumab should be used during pregnancy only if the benefits to the mother outweigh the risks to the mother/unborn child.

Background and AimsMedical management of fistulising Crohn’s disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4β7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692].MethodsExploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates.ResultsAt entry into the maintenance period, 153 [33%] patients had a history of fistulising disease and 57 [12%] patients had ≥1 active draining fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO-treated patients (95% confidence interval [CI], –11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction [ARR]: 19.7%; 95% CI, –8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54–11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059–0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates.ConclusionsOur findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.

SUMMARY BackgroundChronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer).