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Background & Aims: There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody against the integrin α4β7, as induction therapy., Methods: Patients with moderately to severely active CD (CD activity index [CDAI] score, 220-400 points) were assigned randomly to groups given vedolizumab (300 mg) or placebo intravenously at weeks 0, 2, and 6. The primary analysis involved 315 patients with previous TNF antagonist failure (ie, an inadequate response to, loss of response to, or intolerance of ≥1 TNF antagonists); we determined the proportion of patients in clinical remission (CDAI, ≤150 points) at week 6. Secondary analyses evaluated outcomes at weeks 6 and 10 in this population and in the overall population (N = 416), which included patients naive to TNF antagonist therapy (n = 101)., Results: Among patients who had experienced previous TNF antagonist failure, 15.2% of those given vedolizumab and 12.1% of those given placebo were in remission at week 6 (P = .433). At week 10, a higher proportion of this population given vedolizumab was in remission (26.6%) than those given placebo (12.1%) (nominal P = .001; relative risk, 2.2; 95% confidence interval, 1.3-3.6). A higher proportion of patients with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response (≥100-point decrease in CDAI score from baseline) at week 6 than those given placebo (39.2% vs 22.3%; nominal P = .001; relative risk, 1.8; 95% confidence interval, 1.2-2.5). Adverse event results were similar among all groups., Conclusions: Vedolizumab was not more effective than placebo in inducing clinical remission at week 6 among patients with CD in whom previous treatment with TNF antagonists had failed. The therapeutic benefits of vedolizumab in these patients were detectable at week 10. ClinicalTrials.gov number: NCT01224171., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Clinicians are increasingly utilizing noninvasive serologic tests for the diagnosis and screening of celiac disease (CD). The aim of this study was to conduct a systematic review of the diagnostic performance of serologic tests for the diagnosis and screening of CD. Standard systematic review methodology was used. A literature search was conducted in MEDLINE (1966 to October 2003) and EMBASE (1974 to December 2003) databases. A weighted mean of the sensitivity and specificity along with 95% confidence intervals and summary receiver operating characteristic (ROC) curves were calculated. The pooled specificity of endomyseal antibody (EMA)-monkey esophagus (ME) or EMA-human umbilical cord (HU) was close to 100% in adults and children. The pooled specificity of transglutaminase antibody (tTG)-guinea pig (GP) and tTG-human recombinant (HR) were between 95% and 99%. IgA-EMA-ME demonstrated sensitivities of 96% and 97% in children and adults, respectively. EMA-HU demonstrated a similar sensitivity of 97% in children but 90% in adults. The pooled sensitivity of tTG-GP in adults and children was 90% and 93%, respectively. The sensitivity of tTG-HR was 98% and 96%, respectively. The performance of antigliadin antibody was inferior to that of EMA and tTG. EMA and tTG offer high sensitivity and specificity. The sensitivity of these tests appears to be lower than reported when milder histologic grades are used to define CD (below 90%). If true, the nearly perfect negative predictive value of these tests would drop. The positive predictive value of these tests is likely lower than reported when the tests are applied in low-prevalence populations.

Until recently, celiac disease (CD) was felt to be a rare disease in the United States. The aim of this study was to conduct a systematic review of the prevalence of CD in general Western populations and in populations at high risk for CD. Standard systematic review methodology was used. A literature search was conducted in MEDLINE (1966 to October 2003) and EMBASE (1974 to December 2003) databases. Qualitative and quantitative prevalence estimates were produced after assessing study heterogeneity. The prevalence of CD in general Western populations is close to 1% and is somewhat higher in certain Western European populations. The prevalence of CD in populations at risk for CD is as follows: 3%-6% in type 1 diabetic patients, up to 20% in first-degree relatives, 10%-15% in symptomatic iron-deficiency anemia (IDA), 3%-6% in asymptomatic IDA, and 1%-3% in osteoporosis. The prevalence of CD in patients suspected of having CD varied depending on the reasons for suspecting CD and on whether the study was conducted in a referral center. In general, the prevalence ranged from 5% to 15%, but was up to 50% in symptomatic patients evaluated in a tertiary referral center. CD is a common medical condition. The prevalence is higher still in high-risk groups. Clinicians in a variety of specialties should have a high index of suspicion for the diagnosis of CD and in particular need to pay close attention to the identified high-risk groups.

Population screening studies have identified that up to two thirds of celiac disease (CD) cases are asymptomatic. The aim of this study was to conduct a systematic review of the expected consequences of testing for CD in the following populations: (1) patients with symptoms suggestive of CD, (2) asymptomatic at-risk populations, and (3) general population. Standard systematic review methodology was used. A comprehensive literature search was conducted in MEDLINE (1996-2003), EMBASE (1974-2003), CAB (1972 forward), PsychINFO (1840-2003), AGRICOLA (1970-2003), and Sociological Abstracts (1963 forward); searches were conducted in December 2003. Pooled summary estimates were not calculated. The majority of the included studies were before-after studies, case control, or retrospective cohorts. The quality of evidence for the before-after studies is weaker. The overall strength of the evidence for this issue was fair to good. This area of research is relatively new, and further high-quality studies are required. The consequences of testing for celiac disease in symptomatic individuals appears to have a positive impact on patient-relevant outcomes. The data are less clear for those with silent CD or those with lower grade histologic lesions in small bowel biopsy. The literature suggests that compliance is less than ideal in these individuals, especially if diagnosed when adults. Long-term outcomes have not been extensively studied in those with silent CD.