0000000000241212
AUTHOR
Livia Biancone
Infliximab in the treatment of Crohn's disease: Predictors of response in an Italian multicentric open study
Abstract Background. Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. Aims. To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. Patients and methods. Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI) > 220–400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endp…
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.
Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up
Background Severe ulcerative colitis is a life-threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy. Aim To evaluate short- and long-term effectiveness and safety of infliximab in severe refractory ulcerative colitis. Methods Eighty-three patients with severe ulcerative colitis (i.v. glucocorticoids treatment-refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short-term outcome was colectomy/death 2 months after the first infusion. Long-term outcome was survival free from colectomy. Safety data were recorded. Resu…
Real-life effectiveness of ustekinumab in inflammatory bowel disease patients with concomitant psoriasis or psoriatic arthritis: An IG-IBD study
Abstract Background Few data exist regarding the effectiveness of ustekinumab in inflammatory bowel disease (IBD) patients treated for concomitant psoriasis or psoriatic arthritis. Aims to describe the outcomes of IBD patients who received subcutaneous ustekinumab through a dermatological or rheumatological prescription. Methods This multicenter, retrospective study included all IBD patients who were started on ustekinumab for concomitant active psoriasis/ psoriatic arthritis, irrespective of IBD activity. The primary endpoint was overall ustekinumab persistence, defined as the maintenance of therapy because of sustained clinical benefit for IBD. Results Seventy patients (64 Crohn’s disease…
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…
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…
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…
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…
Infliximab three-dose induction regimen in severe corticosteroid-refractory ulcerative colitis: Early and late outcome and predictors of colectomy
Abstract Background Infliximab is effective as rescue therapy in severe corticosteroid-refractory ulcerative colitis. The optimal dose regimen and the long term benefits are not well defined. The aim of the present study was to evaluate short- and long-term colectomy rate in a cohort of patients with severe corticosteroid-refractory ulcerative colitis who received a three-dose infliximab induction regimen. Methods One hundred and thirteen patients admitted to 11 Italian IBD referral centres and treated with infliximab according to an intention to treat three-dose regimen were included. The co-primary endpoints were 3- and 12-month colectomy rate. The secondary end-points were the overall co…