Citations

Background: Vedolizumab (VDZ) is a gut-specific α4-β7 integrin antagonist that has demonstrated efficacy in Crohn’s disease (CD) and ulcerative colitis (UC). The safety of VDZ in the perioperative period remains unclear. The aim of this study was to evaluate postoperative complications and perioperative safety in VDZ-treated patients undergoing nonintestinal operations. Methods: A case-matched study was performed at two inflammatory bowel disease (IBD) referral centers. Adult patients with CD and UC who underwent a nonintestinal surgical procedure during treatment with VDZ were included. Patients who had their last VDZ infusion up to 12 weeks before the procedure were considered exposed and were matched in a 1:1 ratio to patients without VDZ therapy, according to type of surgical procedure, age, and sex. The primary outcome was overall risk of early postoperative infectious complications (up to 30 days after surgery), readmissions, reoperations, surgical site infections, and other infections. The VDZ and control groups were subsequently compared using the Pearson χ2 test and Wilcoxon rank sum. Results: We identified 34 patients treated with VDZ who underwent 36 nonintestinal surgical procedures. These patients were matched with 36 control procedures. Postoperative complications were not different between the VDZ-treated and control cohorts for all outcomes analyzed: infectious complications occurred in 14% versus 8% ( p = 0.45), superficial surgical site infections 6% versus 0% ( p = 0.15), reoperations 6% versus 3% ( p = 0.56) and readmissions 11% versus 6% ( p = 0.37). Conclusions: VDZ-treated patients with IBD undergoing nonintestinal procedures did not have an increased risk of overall postoperative infections or other complications compared with matched controls.

Summary Background Regulatory requirements for claims of mucosal healing in ulcerative colitis ( UC ) will require demonstration of both endoscopic and histologic healing. Quantifying these rates is essential for future drug development. Aims To meta‐analyse endoscopic and histologic placebo response and remission rates in UC randomised controlled trials ( RCT s) and identify factors influencing these rates. Methods MEDLINE , EMBASE and the Cochrane Library were searched from inception to March 2017 for placebo‐controlled trials of pharmacological interventions for UC . Endoscopic and histologic placebo rates were pooled by random effects. Mixed effects univariable and multivariable meta‐regression was used to evaluate the influence of patient, intervention and trial‐related study‐level covariates on these rates. Results Fifty‐six induction (placebo n = 4171) and 8 maintenance trials (placebo n = 1011) were included. Pooled placebo endoscopic remission and response rates for induction trials were 23% [95 confidence interval ( CI ) 19‐28%] and 35% [95% CI 27‐42%] respectively, and 20% [95% CI 16‐24%] for maintenance of remission. The pooled histologic placebo remission rate was 14% [95% CI 8‐22%] for induction trials. High heterogeneity was observed for all outcomes ( I 2 56.2%‐88.3%). On multivariable meta‐regression, central endoscopy reading was associated with significantly lower endoscopic placebo remission rates (16% vs 25%; OR = 0.52, [95% CI 0.29‐0.92], P = 0.03). On univariable meta‐regression, higher histologic placebo remission was associated with concomitant corticosteroids ( OR = 1.17 [95% CI 1.08‐1.26], P < 0.0001, per 10% increase in corticosteroid use). Conclusions Placebo endoscopic and histologic rates range from 14% to 35% in UC RCT s but are highly heterogeneous. Outcome standardisation may reduce heterogeneity and is needed in this field.

Perianal fistulae in patients with Crohn’s disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

Background and aim Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC. Methods Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute. Results For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities. Conclusions Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

Objective Vedolizumab is a gut-selective antibody to α 4 β 7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We report an integrated summary of the safety of vedolizumab. Design Safety data (May 2009–June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. Results In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p<0.0001), corticosteroid (HR, 1.88; 95% CI 1.35 to 2.63; p=0.0002) or narcotic analgesic use (HR, 2.72; 95% CI 1.90 to 3.89; p<0.0001). Investigator-defined infusion-related reactions were reported for ≤5% of patients in each study. Eighteen vedolizumab-exposed patients (<1%) were diagnosed with a malignancy. Conclusions Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period. Trial registration number NCT01177228, NCT00619489 , NCT00783718 , NCT00783692 , NCT01224171 , NCT00790933 .