Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy.

BACKGROUND: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Fecal Microbial Transplantation impact on gut microbiota composition and metabolome, microbial translocation and T-lymphocyte immune activation in recurrent Clostridium difficile infection patients.

This short communication reports the preliminary results of Fecal Microbial Transplantation (FMT) impact on microbiota, microbial translocation (MT), and immune activation in four recurrent Clostridium difficile infection (R-CDI) patients. After FMT a restore of gut microbiota composition with a significant increase of fecal acetyl-putrescine and spermidine and fecal acetate and butyrate, a decrease of immune activation of T cells CD4+ and CD8+levels, and of LPS binding protein (LBP) level, were observed. Preliminary results indicate that FMT seems to be helpful not only as a CDI radical cure, with an impact on fecal microbiota and metabolome profiles, but also on MT and immune activation.

The safety of biological pharmacotherapy for the treatment of ulcerative colitis.

INTRODUCTION: Biological agents are effective in ulcerative colitis (UC). Currently, 3 anti-TNF agents (infliximab, adalimumab, and golimumab) and 1 anti-integrin agent (vedolizumab) are approved for the treatment of UC. The mechanism of action of biologic agents can also give rise to several side effects, some even serious. It remains uncertain to what extent biologic treatments may be associated with an increased rate of infections, malignancies and other adverse events Areas covered: Our aim is to review the relevant data available in the literature and briefly summarize the safety profile of biological therapy in UC. We performed a literature search using the OVID, MEDLINE, PUBMED and EMBASE databases. Also other relevant sources of safety data were also used. Expert opinion: All biological agents currently used in UC are relatively safe. Accurate prevention measures and screening prior to start such therapies, and regular surveillance programs are strongly recommend to minimize any risk of infections, malignancy and other adverse events related to the use of monoclonal antibodies in UC patients.

IL-23 Blockade for Crohn s disease: next generation of anti-cytokine therapy.

INTRODUCTION: Adaptive immunity in intestinal inflammation may play a key role in the pathogenesis of Crohn's disease. In particular, interleukin (IL)-23 may be a key mediator in chronic intestinal inflammation by inducing the differentiation of naïve CD4 + T cells into Th17, with the production of several pro-inflammatory cytokines. Furthermore, IL-23 induces interferon-γ (IFN- γ) production from activated T cells, a critical cytokine in innate and adaptive immunity against infections. Areas covered: We aim to review the available data from literature regarding the role of IL-23, with a more specific focus on the recent progresses in the therapeutic modulation of this cytokine. Expert commentary: Increased knowledge regarding the role of IL-23 has allowed for the development of effective therapeutic progresses by blocking the IL-23 mediated pathways. Primary or secondary loss of response to anti-TNF therapies in Crohn's disease patients during the first year is widely described in literature: the development of new drugs, with alternative mechanisms of action, is thus a key point to consider for the optimal management of these subjects. Drugs blocking the IL-12/23 pathway showed a good efficacy and safety profile in immune-mediated diseases Further studies are necessary regarding the role of the single blockade of IL-23.

Eubiosis and dysbiosis: the two sides of the microbiota.

The microbial ecosystem of the gastrointestinal tract is characterized by a great number of microbial species living in balance by adopting mutualistic strategies. The eubiosis/dysbiosis condition of the gut microbiota strongly influences our healthy and disease status. This review briefly describes microbiota composition and functions, to then focus on eubiosis and dysbiosis status: the two sides of the microbiota.

Hemostasis in uncontrolled esophageal variceal bleeding by self-expanding metal stents: a systematic review.

AIM: The aim of this systematic review was to evaluate the current reported efficacy and the mortality rate of SEMS treatment in uncontrolled bleeding patients. BACKGROUND: Esophageal variceal bleeding (EVB) represents a life threatening pathology. Despite the adequate pharmacologic and endoscopic treatment, continuous or recurrent bleeding, named as uncontrolled bleeding, occurs in 10-20% of cases. A new removable, covered, and self-expanding metal stent (SEMS) was proposed to control the variceal bleeding. MATERIALS AND METHODS: The study was conducted according to the PRISMA statement. Studies were identified by searching MEDLINE (1989-present) and SCOPUS (1989-present) databases. The last search was run on 01 July 2015. RESULTS: Nine studies (period range=2002-2015) met the inclusion criteria and were included in quantitative analysis. High rate of SEMS efficacy in controling acute bleeding was observed, with a reported percentage ranging from 77.7 to 100%. In 10% to 20% of patients, re-bleeding occurred with SEMS in situ. Stent deployment was successful in 77.8% to 100% of patients while 11 to 36.5% of patients experienced stent migration. CONCLUSION: SEMS could be effective and safe in control EVB and can be proposed as a reliable option to ballon tamponed for patient stabilization and as a bridging to other therapeutic approach.

Th17, intestinal microbiota and the abnormal immune response in the pathogenesis of celiac disease.

Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten in genetically predisposed individuals who carry the HLA-DQ2 or -DQ8 alleles. The immune response is abnormal in celiac disease with small intestinal epithelial damage via CD8+CD4- intraepithelial lymphocytes. The etiology is multifactorial involving genetic and environmental factors, an abnormal immune response, and intestinal dysbiosis. The innate and acquired T-cell mediated immunity play important roles in the pathogenesis of this disease, particularly CD4+ Th17 cells, which have been shown to have critical functions in host defense against bacterial pathogens and in the inflammatory responses to deamidated gluten peptides. We review what is known about the interaction between immune system and intestinal microbiota in the pathogenesis of celiac disease.