Abstract:
BACKGROUND:Improving granulocyte function may represent an effective therapy for Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in children with CD. METHODS:This was multicenter, open-label study in 6-16-year-old patients with moderate to severely active CD. Patients received either 4 or 6 microg/kg SRG subcutaneously daily for 8 weeks, with and without concomitant corticosteroids (CS). The primary endpoint was identification of a safe and tolerable dose in children. The secondary endpoint was establishment of the pharmacokinetics (PK). Efficacy, a tertiary endpoint, was measured by the Pediatric CD Activity Index (PCDAI). Response was defined as a decrease from baseline of > or =12.5 points and remission as absolute PCDAI of < or =10. RESULTS:In all, 22 patients were enrolled: 12 and 10 received 4 and 6 mg/kg, respectively; 19 completed the course. Both doses were found to be safe and well tolerated. Mild injection-site reactions occurred in 90% of patients. Three patients required dose reductions due to elevated absolute neutrophil counts. Following 4 microg/kg the mean area under the curve (AUC) was 2.64 and 2.80 ngh/mL for the 6-11- and 12-16-year-old groups, respectively. The mean half-life (t(1/2)) was 1.22 and 1.59 hours, respectively. Following 6 microg/kg, the mean AUC was 5.01 ngh/mL for the 12-16-year-old group, a 1.8-fold increase. A total of 16/18 patients (88%) achieved remission or response. CONCLUSIONS:Sargramostim at both 4 and 6 mg/kg was well tolerated. PK analysis suggested dose proportionality unaffected by CS exposure. Remission and response data are encouraging, but further trials are needed to assess efficacy.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Kelsen JR,Rosh J,Heyman M,Winter HS,Ferry G,Cohen S,Mamula P,Baldassano RNdoi
10.1002/ibd.21204subject
Has Abstractpub_date
2010-07-01 00:00:00pages
1203-8issue
7eissn
1078-0998issn
1536-4844journal_volume
16pub_type
杂志文章,多中心研究abstract:BACKGROUND:Thiopurines are effective drugs in treating ulcerative colitis (UC) and Crohn's disease (CD) even if studies that specifically investigate these drugs' profile of efficacy in UC compared with CD are scarce. Our aim was to compare the profile of efficacy of thiopurines in patients with UC and CD. METHODS:We ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000538
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/01.mib.0000158386.25660.1e
更新日期:2005-05-01 00:00:00
abstract::The conventional treatment of inflammatory bowel disease (IBD) has focused on nonspecifically targeting mucosal inflammation. In the last decade, with the advent of novel biological agents that directly inhibit proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), rapid progress has been made in clin...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21336
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Extracorporeal photopheresis (ECP) involves ex vivo leukocyte treatment with methoxsalen and UVA light to generate a tolerogenic response. A previous trial demonstrated that ECP permits corticosteroid withdrawal in steroid-dependent Crohn's disease (CD) patients who were in clinical remission. We studied the...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/ibd.23012
更新日期:2013-02-01 00:00:00
abstract::Corticosteroids, and more recently biologics, have been the mainstay of therapy for patients with inflammatory bowel disease. Unfortunately, both are fraught with side effects and limited by lack of efficacy or loss of response. Many patients ultimately succumb to medically refractory disease and require an operation....
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1093/ibd/izy084
更新日期:2018-07-12 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:Epithelial barrier disturbance is thought to contribute to the pathogenesis of inflammatory bowel diseases; however, it remains unclear whether it is a primary defect participating to the onset of inflammation or only a consequence of sustained inflammation. METHODS:A time course study of epithelial barrier...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21211
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND:The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. METHODS:We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North Amer...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa080
更新日期:2020-05-09 00:00:00
abstract::MicroRNAs (miRNAs) are single-stranded RNA molecules, which influence the translation of messenger RNA and hence protein synthesis. The altered expression of miRNAs in disease states in cancer and autoimmune diseases including inflammatory bowel disease is providing new insights into disease pathogenesis. This underst...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000288
更新日期:2015-05-01 00:00:00
abstract::Crohn's disease and ulcerative colitis are quite often complicated with manifestations in extraintestinal organs like joints, eye, and skin. Although the etiopathogenesis of these nonmucosal complications remains unsettled, they all share the characteristic feature of inappropriate leukocyte recruitment in nonlymphati...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.3780040210
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:Several studies suggest an increased risk of venous and arterial thromboembolism (TE) in adults with inflammatory bowel disease (IBD) compared to the general population. We performed a systematic review of studies on incidence and characteristic of TE in children with IBD. METHODS:We searched Medline, LILAC...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21563
更新日期:2011-10-01 00:00:00
abstract::Restorative proctocolectomy with ileal-pouch anal anastomosis (RPC) is the operation of choice for ulcerative colitis (UC) patients requiring surgery. It is also used for patients with familial adenomatous polyposis (FAP). Pouchitis accounts for 10% of pouch failures. It is an idiopathic inflammatory condition that ma...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21911
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In t...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200405000-00002
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences. METHODS:Whole-genome gene expression analys...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e31827eeaa4
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Obesity is associated with systemic and intestine-specific inflammation and alterations in gut microbiota, which in turn impact mucosal immunity. Nonetheless, a specific role of obesity and its interaction with genetics in the progression of Crohn's disease (CD) is unclear. METHODS:We conducted a cross-sect...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000498
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:Chronic inflammation in ulcerative colitis (UC) is a sizeable risk factor for colorectal cancer (CRC). Interleukin-13 (IL-13) is elevated in the UC mucosa and may induce dysregulated signaling in neighboring intestinal epithelial cells (IECs) and thus function as a tumorogenic cytokine. METHODS:Expression o...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,收录出版
doi:10.1002/ibd.21133
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND:Though vedolizumab has received regulatory approval for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) in adults, there is increasing off-label use in children. AIMS:To describe the experience with vedolizumab in pediatric inflammatory bowel disease (IBD) patients at 3 tertiary IBD center...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0000000000000865
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND:We aimed to determine the prevalence of adverse childhood experiences (ACEs) in persons with inflammatory bowel disease (IBD) and whether having ACEs was associated with health care utilization post-IBD diagnosis. METHOD:Three hundred forty-five participants from the population-based Manitoba IBD Cohort Stu...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz054
更新日期:2019-09-18 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:The clinical utility of cellular therapies is being investigated in a broad range of therapeutic areas. This phase 1 study represents the first exploration of PDA001, a preparation of cells cultured from human placental tissue, in subjects with Crohn's disease. METHODS:Twelve subjects with active, moderate-...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0b013e31827f27df
更新日期:2013-03-01 00:00:00
abstract:Introduction:A new clinician-administered inflammatory bowel disease (IBD) Disability Index (IBDDI) was recently developed and validated among a population in France. We aimed to validate the IBDDI in a North American setting and adapt for use as a self-report tool. Methods:Persons 18-65 years old from the population-...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izx063
更新日期:2018-03-19 00:00:00
abstract:BACKGROUND:Mesalamine suppositories are first-line therapy in active ulcerative proctitis; the standard regime still recommends multiple doses per day. The primary objective of this study was to show the noninferiority of once-daily administration of a novel 1 g mesalamine suppository versus thrice-daily administration...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/ibd.21258
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:The clinical course of ulcerative colitis (UC) is unpredictable. During recent years, the ability of fecal biomarkers to predict relapse in inflammatory bowel disease has been evaluated. The objective of this study was to assess fecal calprotectin (FC) as a predictor of disease recurrence in patients with ne...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1097/MIB.0b013e31827e78be
更新日期:2013-03-01 00:00:00
abstract::Chronic inflammatory bowel disease (IBD) presents as two major clinical forms, Crohn's disease (CD) and ulcerative colitis (UC). Genetic epidemiological studies and animal models suggest that inherited factors play significant roles in the susceptibility to both forms of IBD. From four genome-wide scans, putative susc...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-199911000-00005
更新日期:1999-11-01 00:00:00
abstract:Background:Anastomotic recurrence is frequent in patients with Crohn's disease (CD) following ileocecal resection. The degree of endoscopic recurrence, quantified by the Rutgeerts score (RS), is correlated with the risk of clinical and surgical recurrence. Noninvasive modalities such as capsule endoscopy (CE), magnetic...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izx027
更新日期:2017-12-19 00:00:00
abstract:BACKGROUND:Although dysplasia is thought to be the precursor lesion in the development of colitis-associated colorectal cancer (CRC), a significant proportion of patients with ulcerative colitis (UC) and low-grade (LGD) or indefinite (IND) dysplasia remain cancer-free during endoscopic follow-up. There is a need for bi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21722
更新日期:2012-03-01 00:00:00
abstract::Focal infection theory posits that periodontal pathobionts play a causal role in initiating or exacerbating diseases. Periodontal disease is a common inflammatory, multifactorial disease of the periodontal tissues. The main factor for inflammation is mature dental plaque with the presence of pathogens in the microbial...
journal_title:Inflammatory bowel diseases
pub_type: 评论,社论
doi:10.1093/ibd/izz129
更新日期:2020-01-06 00:00:00
abstract::This review examines preclinical and clinical studies relevant to our understanding of how the bidirectional gut-brain axis influences the natural history of inflammatory bowel disease. Preclinical studies provide proof of concept that preexisting behavioral illness, such as depression, results in increased susceptibi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa004
更新日期:2020-03-04 00:00:00
abstract:BACKGROUND:Chronic inflammatory diseases are characterized by massive infiltration of innate and acquired immune cells in inflammatory sites. However, it remains unclear how these cells cooperate in the development of disease. Although bone marrow (BM) is a primary site for hematopoiesis of immune cells except T cells,...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20531
更新日期:2008-11-01 00:00:00
abstract::Colitis-associated colorectal neoplasia (CRN) is a well-known complication of chronic inflammation of the colon either with ulcerative colitis (UC) or colonic Crohn's disease (CD). Studies have shown that inflammatory bowel disease (IBD) patients have an overall higher risk for colorectal dysplasia and cancer compared...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000685
更新日期:2016-05-01 00:00:00