关键词： biologic   Crohn disease   treatment patterns   ulcerative colitis  

摘要： Purpose: Treatment options for patients with ulcerative colitis (UC) or Crohn disease (CD) have increased considerably in recent years with the advent of new biologics, but little is known about treatment pathways in clinical practice. We aimed to characterize treatment patterns and sequences in patients with UC or CD newly initiated on a biologic or an immunosuppressant (IMS). Methods: This retrospective cohort study used US health insurance claims data dated from January 1, 2009, to December 31, 2013, from patients with UC or CD newly initiated on a biologic or an IMS. Treatment patterns and sequences were described during a 24 month follow-up period. Findings: Among 5543 patients with UC and 7561 patients with CD, 2403 and 4677 patients, respectively, were initiated on a biologic;3140 and 2884 patients were initiated on an IMS. In patients initiated on a biologic, monotherapy was chosen in 71% for UC (primarily infliximab [68%]) and in 79% for CD (primarily adalimumab [52%]). Approximately one third of patients remained on the first-line biologic during the follow-up period;69% (UC) and 70% (CD) of patients were initiated on a second-line therapy, among whom 25% (UC) and 39% (CD) received a different biologic monotherapy, suggesting intolerance, inadequate response, or loss of response to first-line therapy. In patients initiated on an IMS, 58% (UC) and 66% (CD) were initiated on monotherapy;combination therapy with a corticosteroid was prescribed in 41% (UC) and 30% (CD) of patients;and second-line therapy was initiated in 72% (UC) and 75% (CD) of patients. (C) 2018 GlaxoSmithKline. Published by Elsevier Inc.

关键词： Infliximab   X-Ray Computed Tomography   Inflammatory Bowel Diseases   Serum   Epitopes   Intestinal Diseases   RUNX1T1 gene   AKR1C4 gene   Patients  

摘要： Aim: To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. Methods: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. Results: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P<0.001). Anti-CT-P13 sera of patients with IBD (n=32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naive individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. Conclusions: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.

关键词： Periodontitis   Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Retrospective cohort study   National Health Insurance Research database  

摘要： Background/purpose: Inflammatory bowel disease (IBD), comprised Crohn's disease and ulcerative colitis, is a mucosal immune response that affects gastroenterological tract. The association between IBD and periodontitis was inconclusive. In this study, we aimed to investigate the association between IBD and periodontitis by using a register-based dataset. Materials and methods: The dataset conducting in this retrospective cohort study was obtained from the National Health Insurance Research database (NHIRD) in Taiwan. For IBD group, conditionally selected control subjects were matched in 1:4 ratio from general population. The risk of periodontitis among IBD group comparing with non-IBD group was calculated by multivariable Cox proportional hazards model. Results: In IBD cohort, 27 IBD patients (7 Crohn's disease and 20 ulcerative colitis) with catastrophic illness registry were identified. 108 controls were selected as non-IBD cohort. The median follow-up period was 3.00 years in the IBD group and 3.15 years in the non-IBD group. The cumulative incidence of IBD was 4.32 per 100,000 persons. After adjusting for several confounding factors, IBD group had higher risk for developing periodontitis than non-IBD group (adjusted HR: 1.82;95% CI: 1.09-3.03). To further stratification with subtype, Crohn's disease group had significantly higher risk of periodontitis (adjusted HR: 3.95;95% CI: 1.59-9.82). Conclusions: Taken together, this retrospective cohort study showed that patients with IBD increase risk of having periodontitis comparing with non-IBD group, especially in Crohn's disease subgroup. (C) 2018 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.

关键词： A-1211212   ABT-737   apoptosis   BCL-2   BIM   IBD   mucosal T cell turnover  

摘要： In inflammatory bowel disease (IBD), inflammation is sustained by an exaggerated response of lymphocytes. This results from enhanced expression of anti-apoptotic B cell lymphoma (BCL-2) and BCL-XL associated with a diminished turnover. Azathioprine (AZA) directly targets BCL-2 family-mediated apoptosis. We investigated whether the BCL-2 family expression pattern could be used to predict treatment response to AZA and determined whether BCL-2 inhibitor A-1211212 effectively diminishes lymphocytes and ameliorates inflammation in a model of colitis. BCL-2 family expression pattern was determined by next-generation sequencing (NGS). BCL-2 inhibitor was administered orally to Il10-/- mice. Haematological analyses were performed with an ADVIA 2120 and changes in immune cells were investigated using quantitative polymerase chain reaction (qPCR) and fluorescence activated cell sorter (FACS). We determined similar expression levels of BCL-2 family members in patients with remission and patients refractory to treatment, showing that BCL-2 family expression can not predict AZA treatment response. Expression was not correlated with the modified Truelove and Witts activity index (MTWAI). BCL-2 inhibitor initiated cell death in T cells from patients refractory to AZA and reduced lymphocyte count in Il10-/- mice. FACS revealed diminished CD8(+) T cells upon BCL-2 inhibitor in Il10-/- mice without influencing platelets. Tnf, Il1, Ifn? and Mcp-1 were decreased upon BCL-2 inhibitor. A-1211212 positively altered the colonic mucosa and ameliorated inflammation in mice. Pro-apoptotic BCL-2 inhibitor A-1211212 diminishes lymphocytes and ameliorates colitis in Il10-/- mice without inducing thrombocytopenia. BCL-2 inhibition could be a new therapy option for patients refractory to AZA.

摘要： The article focuses on study conducted that stresses inflammatory bowel diseases (IBD) associated with number of extraintestinal manifestations (EIMs). According to the author, these could result in greater morbidity than underlying intestinal disease. The article discusses that the study was conducted during the 10‑year study period in Saudi Arabia.

摘要： The article discusses the impact of the genetic and genomics tools in the treatment of inflammatory bowel disease (IBD). It talks about the treatment of ulcerative colitis or Crohn's disease (CD). It discusses the aspects of human leukocyte antigen. It discusses the area of pharmacogenetics and the steady development in the field.

关键词： children   Crohn's disease   neutrophil extracellular traps   ulcerative colitis  

摘要： Neutrophil extracellular traps (NETs) are fibers composed of chromatin and neutrophil proteins released by activated neutrophils. NETs trap and kill microbes, activate dendritic and T cells, and are implicated in autoimmune and vascular diseases. The pathogenesis of inflammatory bowel disease (IBD) is multifactorial and characterized by chronic active mucosal inflammation with controversial contribution of neutrophils. Our aim is to describe the involvement of NETs in pediatric IBD. We retrospectively examined biopsies from the small bowel and colon of children at diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). The biopsies were labeled for neutrophil elastase, myeloperoxidase, DNA, chromatin and histones in order to identify NETs. Samples of two children with normal colonoscopy served as controls. Twelve patients (5 boys) were included, 6 with CD and 6 with UC. Their average age was 12.2 years (range 5-16). NETs were found in all samples from patients and not in the samples from the two controls. This is the first demonstration of the presence of NETs in biopsies taken from the small bowel and colon of pediatric patients with IBD. More studies are needed in order to identify the role of NETs in CD/UC pathogenesis.

关键词： Genes   Inflammatory Bowel Diseases   Intestinal Diseases  

摘要： The article discusses the genetic factors which cause inflammatory bowel disease like Crohn's disease and ulcerative colitis.

关键词： INFLAMMATORY bowel diseases   IMMUNODEFICIENCY   EPITHELIAL cells   HOMEOSTASIS   ISLANDS of Langerhans  

摘要： The incidence of inflammatory bowel disease (IBD) is increasing worldwide, most notably in young children. The development of disease is a combination of several factors, including genetics, environment, the microbiota, and immune system. Recently, next-generation sequencing has allowed for the identification of novel genetic causes for intestinal disease, including pediatric inflammatory bowel disease (IBD). These IBD genes can generally be grouped into genes causing either primary immunodeficiency or intestinal epithelial defects (the focus of this review). Most of these genes have been functionally validated with in vitro and/or animal models, and have been demonstrated to cause intestinal disease. Intestinal epithelial IBD genes are of particular interest since they are the least amenable to current therapies;therefore, further research is warranted to develop potential therapies. A number of cellular pathways are impacted with intestinal epithelial IBD genes, including intestinal epithelial cell adhesion and generation of reactive oxygen species. Here, we describe the currently known IBD risk alleles and monogenic causal intestinal epithelial genes, their putative roles in preserving intestinal epithelial cell homeostasis, and their implications for IBD pathophysiology.