Adalimumab for the treatment of fistulas in patients with Crohn’s disease

To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn's disease (CD). A phase III, multicentre, randomised, double-blind, placebo controlled study with an open-label extension was conducted in 92 sites. A subgroup of adults with moderate to severely active CD (CD activity index 220-450) for >or=4 months who had draining fistulas at baseline. All patients received initial open-label adalimumab induction therapy (80 mg/40 mg at weeks 0/2). At week 4, all patients were randomly assigned to receive double-blind placebo or adalimumab 40 mg every other week or weekly to week 56 (irrespective of fistula status). Patients completing week 56 of therapy were then eligible to enroll in an open-label extension. Complete fistula healing/closure (assessed at every visit) was defined as no drainage, either spontaneous or with gentle compression. Of 854 patients enrolled, 117 had draining fistulas at both screening and baseline (70 randomly assigned to adalimumab and 47 to placebo). The mean number of draining fistulas per day was significantly decreased in adalimumab-treated patients compared with placebo-treated patients during the double-blind treatment period. Of all patients with healed fistulas at week 56 (both adalimumab and placebo groups), 90% (28/31) maintained healing following 1 year of open-label adalimumab therapy (observed analysis). In patients with active CD, adalimumab therapy was more effective than placebo for inducing fistula healing. Complete fistula healing was sustained for up to 2 years by most patients in an open-label extension tria

Review article: defining remission in ulcerative colitis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87130/1/j.1365-2036.2011.04701.x.pd

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-alpha drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNF alpha drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.info:eu-repo/semantics/publishedVersio

Exclusive enteral nutrition induces early clinical, mucosal and transmural remission in paediatric Crohn's disease

Background and aims: Exclusive enteral nutrition (EEN) induces clinical and mucosal healing (MH) in Crohn's disease (CD), with MH the best determinant of future outcome. We investigated efficacy of EEN for inducing early clinical, biochemical, mucosal and transmural remission of CD and related early endoscopic response to outcomes at 1 year. Methods: In a prospective, open label study 34 children (mean 13.1 years; 21 males) with new diagnosis CD were offered EEN, 26 completed a minimum 6 weeks EEN and underwent paired clinical, biochemical and endoscopic assessment at start and completion using PCDAI, BMI, CRP and Simple Endoscopic Score for CD (SES-CD). A subset, 16/26, had paired MR enterography scored. Early good endoscopic response (complete MH, or near complete, SES-CD 0-3) was related to outcome at 1 year. Results: EEN improved mean PCDAI (37.88-7.01, p < 0.001; BMI Z scores (-1.54 to -0.54, p < 0.01); weight Z score (-0.79 to -0.08, p < 0.03); CRP (44.86-5.5, p < 0.001); endoscopy (SES-CD 14.28-3.88, p < 0.001) and MRE (5.14-2.79, p = 0.01). Of 26 children, 22 (84 %) achieved clinical remission; 20 (76 %) biochemical remission. Fifteen (58 %) had early good endoscopic response (11 complete, 4 near complete MH) and 3/14 (21 %) had complete transmural remission of ileal CD (MRE-CD: 0-1). Early good endoscopic response was associated with reduced endoscopic confirmed relapse (53 vs. 100 %, p = 0.02), anti-TNF use (33 vs. 88 %, p = 0.01) and hospitalisation (40 vs. 88 %) at 1 year. Conclusions: EEN is effective for inducing early clinical, biochemical, mucosal and transmural remission. Early endoscopic remission improves outcomes at 1 year

Bowel ultrasound measurements in healthy children — systematic review and meta-analysis

Background: Ultrasound (US) is a noninvasive method of assessing the bowel that can be used to screen for bowel pathology, such as Inflammatory Bowel Disease, in children. Knowledge about US findings of the bowel in healthy children is important for interpreting US results in cases where disease is suspected. Objective: To assess the bowel wall thickness in different bowel segments in healthy children and to assess differences in bowel wall thickness among pediatric age categories. Materials and methods: We conducted a systematic search in the PubMed, Embase, Cochrane, and CINAHL databases for studies describing bowel wall thickness measured by transabdominal US in healthy children. We excluded studies using contrast agent. We calculated the pooled mean and standard deviation scores and assessed differences among age categories (0–4 years, 5–9 years, 10–14 years, 15–18 years), first with analysis of variance (ANOVA) and further with subsequent Student’s t-tests for independent samples, corrected for multiple testing. Results: We identified 191 studies and included 7 of these studies in the systematic review. Reported bowel wall thickness values ranged from 0.8 mm to 1.9 mm in the small bowel and from 1.0 mm to 1.9 mm in the colon. The mean colonic bowel wall thickness is larger in children ages 15–19 years compared to 0–4 years (range in difference: 0.3–0.5 mm [corrected P<0.02]). Conclusion: The reported upper limit of bowel wall thickness in healthy children is 1.9 mm in the small bowel and the colon, and mean thickness increases slightly with age in jejunum and colon. These values can be used as guidance when screening for bowel-related pathology in children