Abstract:
BACKGROUND:Vedolizumab is a gut-selective biologic that has shown efficacy in ulcerative colitis (UC) and Crohn's disease (CD). We studied the pharmacokinetics, pharmacodynamics, safety, tolerability, and efficacy of a new formulation of vedolizumab produced by an improved manufacturing process. METHODS:UC patients were randomized to receive vedolizumab (2, 6, or 10 mg/kg) or placebo on days 1, 15, 29, and 85. Safety, pharmacokinetics, pharmacodynamics, and immunogenicity evaluations were performed at multiple timepoints through day 253. Partial Mayo Scores and fecal calprotectin levels were used to assess efficacy. RESULTS:In all, 46 patients (9 placebo, 37 vedolizumab) received at least one dose of study medication. The vedolizumab serum concentration declined monoexponentially until concentrations reached 1-10 μg/mL, and then fell nonlinearly. Vedolizumab maximum serum concentration (C(max) ) and area under the curve (AUC) increased approximately proportionally as a function of dose. Vedolizumab maximally saturated α(4) β(7) receptors on peripheral serum lymphocytes at all measurable serum concentrations. Vedolizumab was well tolerated, with no deaths and no adverse events leading to discontinuation. At every assessment from day 29 through day 253, over 50% of vedolizumab-treated patients were in clinical response, while placebo response rates generally ranged between 22% and 33%. Vedolizumab treatment reduced fecal calprotectin levels compared with placebo. CONCLUSIONS:Vedolizumab demonstrated dose-proportional pharmacokinetics and maximally saturated α(4) β(7) receptors over the tested dose range. Multiple dosing up to 10 mg/kg was well tolerated. Over the course of follow-up a greater proportion of patients treated with vedolizumab were in clinical response than those who were assigned to placebo.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Parikh A,Leach T,Wyant T,Scholz C,Sankoh S,Mould DR,Ponich T,Fox I,Feagan BGdoi
10.1002/ibd.21896subject
Has Abstractpub_date
2012-08-01 00:00:00pages
1470-9issue
8eissn
1078-0998issn
1536-4844journal_volume
18pub_type
杂志文章,随机对照试验abstract:BACKGROUND:The purpose of the study was to determine the role of fecal calprotectin and lactoferrin in the prediction of inflammatory bowel disease relapses, both in patients with ulcerative colitis (UC) and Crohn's disease (CD), in a large, long-term, follow-up study. METHODS:The prospective multicenter study include...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1002/ibd.20933
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel disease (IBD) is associated with a high risk of deep venous thromboembolism. However, few data are available so far on portomesenteric vein thrombosis (PMVT). The aim of this study was to describe the characteristics of PMVT in patients with IBD. METHODS:A retrospective study was conducte...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0b013e31827eea5f
更新日期:2013-03-01 00:00:00
abstract::Induction and maintenance of remission, mucosal healing, the avoidance of surgical intervention, and decreasing the likelihood of cancer developing are the primary therapeutic goals in ulcerative colitis (UC). For the traditional therapies, 5-aminosalicylic acid (including mesalamine), corticosteroids, and thiopurines...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.20797
更新日期:2009-06-01 00:00:00
abstract::Potential biomarkers for Crohn's disease (CD) and ulcerative colitis (UC) were identified from two sets of full thickness pathologic samples utilizing DermArray and PharmArray DNA microarrays relative to uninvolved (Un) colon or normal colon. Seven of the over-expressed genes were verified using quantitative RT-PCR (i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200401000-00001
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Chemokines regulate the pathways that restrict homing of specific subsets of immune cells, and thereby fine tune the immune response at specific lymphoid and peripheral tissues. CCL2 is a chemokine that induces migration of monocytes, memory T cells, and dendritic cells. Previously, we demonstrated that pM l...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21254
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:A total of 254 senior consultant gastroenterologists with valid e-mail addresses were identified from the membership list of the British Society of Gastroenterology (BSG) 2007. METHODS:They were sent by e-mail a questionnaire which dealt with aspects of clinical practice and addressed cancer prevention in u...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20750
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:Disappearance of macroscopic mucosal inflammation predicts long-term outcome in Crohn's disease (CD). It can be assessed by ileocolonoscopy, which is, however, an invasive and expensive procedure. Disease activity indices do not correlate well with endoscopic activity and noninvasive markers have a low sensi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000436
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:The etiology of ulcerative colitis (UC) and Crohn's disease (CD) involves both genetic and environmental components. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. These studies have also highlighted the presence of genes com...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1097/MIB.0b013e3182810041
更新日期:2013-02-01 00:00:00
abstract::Ulcerative colitis and Crohn's disease both confer an increased risk of developing colorectal cancer. The use of 5-aminosalicylate as a remission-inducing agent has been long accepted. Its use as a potential chemoprophylactic agent has been proposed and is used by some practitioners. This review examines the most rece...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.20186
更新日期:2007-10-01 00:00:00
abstract:Background:Cancer and death are the most severe outcomes that affect patients with inflammatory bowel disease (IBD). These outcomes are even more severe if they occur at a young age but are rare, even in the general population. We conducted a systematic review to provide an overview of all reported pediatric (PIBD) pat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izx104
更新日期:2018-03-19 00:00:00
abstract:BACKGROUND:Little knowledge exists about the association between anti-tumor necrosis factor-alpha (anti-TNF-α) therapy for inflammatory bowel disease during late pregnancy and adverse birth outcomes. We aimed to examine whether treatment with anti-TNF-α during the third trimester affected preterm birth and low birth we...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001234
更新日期:2017-11-01 00:00:00
abstract:INTRODUCTION:Antitumor necrosis factor (anti-TNF) medications are known to be highly efficacious in persons with moderate-to-severe inflammatory bowel disease (IBD). There is a paucity of data from population-based sources to elucidate persistence with these medications in the general population of IBD. Discontinuation...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001025
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21537
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Genetic predisposition as a cause of inflammatory bowel disease (IBD) has been proven by both family and twin studies and genetic variants associated with the disease have been identified. The aim of our study was to determine the concordance rates for IBD in German twin pairs and to evaluate clinical charac...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20380
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:Many patients with Crohn's disease (CD) are treated with medications, including steroids, immunomodulators, and anti-tumor necrosis factor alpha (anti-TNF-α) agents, at the time of surgery. This study evaluated the effects of these medications on postoperative complications in CD patients. METHODS:This retr...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz010
更新日期:2019-08-20 00:00:00
abstract:BACKGROUND:The dsRNA-activated protein kinase (PKR) phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), a global regulator of protein synthesis in mammals. In addition, PKR activates several signal transduction pathways including STAT3 and AKT. PKR is activated by a number of inflammator...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.22878
更新日期:2012-09-01 00:00:00
abstract:Background and aims:The postoperative course of Crohn's disease (CD) is best predicted by ileocolonoscopy. Ultrasonography (US) has been proposed as indicator for postsurgical recurrence (PSR), but further confirmation is needed. We performed a systemic review with meta-analysis to assess the pooled diagnostic accuracy...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izy012
更新日期:2018-04-23 00:00:00
abstract:INTRODUCTION:No study to date has evaluated perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) in pediatric inflammatory bowel disease-unclassified (IBDU) as compared with Crohn's colitis (CC) and ulcerative colitis (UC), which represent the diagnostic challenge. W...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0000000000000784
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency disorder characterized by inability of phagocytes to kill certain bacteria and fungi. Histology from colon biopsies of CGD patients have shown the presence of inflammation and granulomas, almost indistinguishable from the findings seen ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20890
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:Circulating chromogranin A (CgA) levels, a marker for neuroendocrine tumors including carcinoids, have recently been found elevated in some patients with inflammatory bowel disease (IBD), although their significance is unclear. Therefore, we aimed to evaluate CgA levels and their possible relationship with c...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20851
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Assimilation of the preferred nutrient of enterocytes is mediated primarily by sodium (Na)-dependent cotransport (NGct) in the intestine. The predominant NGcT in villus cells, B0AT1, is inhibited secondary to a decrease in cotransporter numbers during chronic intestinal inflammation. In contrast, NGcT mediat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.22924
更新日期:2012-11-01 00:00:00
abstract::Crohn's disease (CD) leads to the development of complications through progressive uncontrolled inflammation and the transmural involvement of the bowel wall. Most of the available literature on penetrating CD focuses on the perianal phenotype. The management of nonperianal penetrating complications poses its own set ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1093/ibd/izx108
更新日期:2018-03-19 00:00:00
abstract:BACKGROUND:Clostridium difficile infection (CDI) and Cytomegalovirus (CMV) reactivation are associated with disease exacerbations and poor outcomes in inflammatory bowel disease (IBD). Therefore, we assessed the association between these organisms in patients with IBD and the impact on colectomy. METHODS:A retrospecti...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000939
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Apolipoprotein E (ApoE) mediates potent antiinflammatory and immunomodulatory properties in addition to its roles in regulating cholesterol transport and metabolism. However, its role in the intestine, specifically during inflammation, is largely unknown. METHODS:Mice (C57BL/6 or ApoE-deficient [ApoE-KO] mi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000699
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:Differentiating ulcerative colitis (UC) from Crohn's colitis (CC) can be difficult and may lead to inaccurate diagnoses in up to 30% of inflammatory bowel disease (IBD) patients. Much of the diagnostic uncertainty arises from the overlap of clinical and histologic features. Matrix-assisted laser desorption/i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21442
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:The dinitrofluorobenzene/dinitrosulfonic acid (DNFB/DNS) model was originally described as an experimental model of intestinal inflammation resembling human ulcerative colitis (UC). Due to the absence of acceptable UC experimental models for pharmacological preclinical assays, here we examine the immune resp...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21586
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Surgery is the preferred option for patients with symptomatic localized fibrostenotic ileocecal Crohn's disease (CD) but not for those with predominantly active inflammation without obstruction. The benefit of early surgery in patients with a limited nonstricturing ileocecal CD over biologic treatment is sti...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz282
更新日期:2020-10-23 00:00:00
abstract:BACKGROUND:Chronic ulcerative colitis (UC) is associated with an increased colorectal cancer risk which may be secondary to repetitive mucosal injury. Both epigenetic methylation and the classic adenoma-to-carcinoma sequence have been implicated in this malignant transformation, but the underlying molecular mechanisms ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21526
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Host-microbe interactions at the intestinal mucosal-luminal interface (MLI) are critical factors in the biology of inflammatory bowel disease (IBD). METHODS:To address this issue, we performed a series of investigations integrating analysis of the bacteria and metaproteome at the MLI of Crohn's disease, ulc...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21793
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Children with Crohn's disease (CD) suffer from malnutrition. Understanding substrate utilization during exercise may help patients with CD sustain a healthy active lifestyle without compromising nutrition. The aim of this study was to determine whether substrate utilization and bioavailability during exercis...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000436958.54663.4f
更新日期:2013-11-01 00:00:00