0000000000014058
AUTHOR
Sandro Ardizzone
Variants of CARD15 are associated with an aggressive clinical course of Crohn's Disease. An IG-IBD Study
Three major variants of the CARD15 gene confer susceptibility to Crohn's disease (CD). Whether or not these variants correlate with specific clinical features of the disease is under evaluation.We investigated the possible association of CARD15 variants with specific clinical characteristics, including the occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA), in a large cohort of inflammatory bowel disease (IBD) patients and their unaffected relatives.Three hundred and sixteen CD patients (156 with positive family history), 408 ulcerative colitis (UC) patients (206 with positive family history), 588 unaffected relatives, and 205 unre…
Use of corticosteroids and immunosuppressive drugs in inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease
Abstract The two main forms of intestinal bowel disease, namely ulcerative colitis and Crohn’s disease, are not curable but can be controlled by various medical therapies. The Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. The guidelines consider therapies that induce remission in patients with active disease as well as treatment regimens that maintain remission. These guidelines complement already existing guidelines from IG-IBD on the use of biological drugs in patients with inflammatory bowel diseases.
Physicians’ Knowledge and Application of Immunization Strategies in Patients with Inflammatory Bowel Disease: A Survey of the Italian Group for the Study of Inflammatory Bowel Disease
<b><i>Background:</i></b> No data on European countries about knowledge and application of immunization strategies in patients with inflammatory bowel disease (IBD) are available. <b><i>Objectives:</i></b> We designed a questionnaire aimed at exploring these issues among Italian gastroenterologists dealing with adult and paediatric IBD. <b><i>Methods:</i></b> An anonymous, 24-item, questionnaire was sent via e-mail to all members of the Italian Group for the study of Inflammatory Bowel Disease. Three sets of questions were formulated: (1) Characteristics of respondents; (2) General opinions on the role of vaccines in IB…
Advanced age is an independent risk factor for severe infections and mortality in patients given anti-tumor necrosis factor therapy for inflammatory bowel disease.
See related article, Oostlander AE et al, on page 116 in Gastroenterology. BACKGROUND & AIMS: Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis factor (TNF) inhibitors in these patients. METHODS: We collected data from patients with IBD treated with infliximab (n 2475) and adalimumab (n 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn’s disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 yea…
Anti-tumour necrosis factor-α antibodies and B cell homeostasis in human inflammatory bowel diseases
Background The expression of CD70 on T cells is greatly enhanced by antigen-presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)-α, which is constitutionally high in patients with inflammatory bowel disease (IBD). Experimentally, the chronic activation of CD27 as a result of the constitutive expression of CD70 leads to the demise of B cells in bone marrow (BM) and the secondary lymphoid organs. The aim of this study was to assess the number and phenotype of circulating B cell in untreated IBD patients and their counterparts treated with biological anti-TNF drugs. Methods The study involved 13 untreated IBD patients, 36 IBD patients treated with biological drugs, and…
Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease
Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activit…
Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy.
AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed < 19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The f…
PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability
Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn’s disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 express…
Late-onset Crohn's disease: a comparison of disease behaviour and therapy with younger adult patients: the Italian Group for the Study of Inflammatory Bowel Disease 'AGED' study
BACKGROUND Disease phenotype and outcome of late-onset Crohn's disease are still poorly defined. METHODS In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16-39 years and adult-onset Crohn's disease 40-64 years. Data were collected for 3 years following diagnosis. RESULTS A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Syste…
Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas
Abstract Background Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. Patients and Methods In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margi…
Cancer in Crohn's Disease patients treated with infliximab: a long-term multicenter matched pair study
Background: The long-term risk of neoplasia in Crohn's disease (CD) patients treated with infliximab is undefined. The aim was to assess, in a multicenter, matched-pair study, whether infliximab use in CD is associated with an increased frequency of neoplasia in the long term. Methods: A multicenter, long-term, matched-pair study was conducted in 12 referral inflammatory bowel disease (IBD) centers. An initial cohort of 808 CD patients, including 404 infliximab-treated (CD-IFX) and 404 matched CD controls never treated with infliximab (CD-C) studied from 1999 to 2004, was followed up for an additional 4 years (2004–2008). Cases and controls were matched for: sex, age (±5 years), CD site, fo…
Small Bowel Carcinomas in Coeliac or Crohn’s Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium
Background and aims An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. Methods A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. Results CD-SBC showed a significantly better sex-, age-, and st…
The PROSIT Cohort of Infliximab Biosimilar in IBD: A Prolonged Follow-up on the Effectiveness and Safety Across Italy.
BACKGROUND We report a prospective, nationwide cohort evaluating the safety and effectiveness of CT-P13. METHODS A structured database was used to record serious adverse events (SAEs), clinical remission/response, inflammatory biomarkers (CRP and calprotectin), and endoscopic findings. RESULTS Eight hundred ten patients with inflammatory bowel disease (IBD) (452 Crohn's disease [CD]) were enrolled. Four hundred fifty-nine patients were naive to anti-TNFα (group A), 196 had a previous exposure (group B), and the remaining 155 were switched to CT-P13 (group C). All patients were included in the safety evaluation with a mean follow-up of 345 ± 215 days and a total number of 6501 infusions. One…