262,401 research outputs found
Precision Medicine in Inflammatory Bowel Diseases
No full textDuring the last decades, a better understanding of the mechanisms sustaining the pathogenic process in inflammatory bowel diseases (IBD) has contributed to expand the therapeutic armamentarium for patients with these disorders. Alongside with traditional therapies, monoclonal antibodies against tumor necrosis factor-alpha, the interleukin (IL)-12/IL-23 p40 subunit and the alpha 4 beta 7 integrin, and tofacitinib, a small molecule inhibiting intracellular pathways downstream to cytokine receptors, have entered into the clinic. However, these drugs are not effective in all patients and some responders can lose response over time. Such a therapeutic failure is, at least in part, dependent on the fact that, in IBD, the tissue damage is driven by simultaneous activation of multiple and distinct immune-inflammatory signals and the detrimental mucosal immune response changes over time even in the same patient. Therefore, personalized approaches aimed at identifying which patient should be treated with a specific drug at a precise time point are worth pursuing. A such approach has the advantage to improve efficacy of the drug and limit adverse reactions, thereby improving quality of the life of the patients and reducing costs. In this review, we summarize all the available evidence about the possible role of precision medicine in IBD
Treatment options for refractory ulcerative colitis: Small molecules, big effects
No full textAlthough the majority of patients with ulcerative colitis (UC) have a mild-to-moderate disease, approximately 10%–15% experience a severe disease course and require immunosuppressive therapies.1 A better understanding of the mechanisms sustaining the pathogenic process in inflammatory bowel diseases (IBD) has largely contributed to expand the therapeutic armamentarium for this group of patients. Alongside with conventional therapies, monoclonal antibodies against tumour necrosis factor-α, α4β7 integrin (vedolizumab), interleukin (IL)-12/IL-23 p40 subunit (ustekinumab), and small molecules inhibiting intracellular pathways downstream to cytokine receptors (tofacitinib, filogotinib and upadacitinib), have entered into the clinic for the treatment of UC.2 However, selecting the appropriate medical therapy for each patient at a given stage of the disease natural history is an increasingly complex task for clinicians, as no prediction for treatment effect can be made in the individual patient
Association Between Celiac Disease and Cancer
No full textCeliac disease (CD) is a chronic enteropathy that develops in genetically susceptible individuals after the ingestion of gluten. There has been a substantial increase in CD prevalence in the last 50 years, and it is now estimated that this disease affects approximately 1% of the population in the Western world. In the large majority of cases, CD is a benign disease, characterized by the complete resolution of symptoms and a normal life expectancy after the onset of a gluten-free diet (GFD). However, failure to adhere to a strict GFD bears the risk of adverse events and increases mortality. A considerable number of studies have considered the possible association between CD and neoplasms. In particular, an increased risk of malignancies, such as cancers of the gastrointestinal tract and intestinal lymphomas, has been reported. In this review, we summarize and discuss the current evidence on the possible association between CD and cancer
Paradoxical hidradenitis suppurativa in Crohn’s disease patients receiving infliximab: a case report and review of literature
No full textThe introduction of TNF blockers in the therapeutic armamentarium of inflammatory bowel diseases (IBD) has largely advanced the way by which clinicians manage these disorders. However, some patients develop de novo immune-mediated diseases during the treatment. We here present the case of paradoxical hidradenitis suppurativa, a chronic inflammatory skin disease characterized by the development of recurrent nodules and abscesses in intertriginous areas, in a 20-year-old, nonsmoker, normal-weight women, with no family history of hidradenitis suppurativa or IBD, diagnosed with nonstricturing nonpenetrating ileocolonic Crohn's disease in 2013, during treatment with infliximab. Infliximab discontinuation was followed by a significant improvement of skin lesions. We also discuss 22 additional cases of paradoxical hidradenitis suppurativa in IBD patients on TNF antagonists reported in the literature with the aim to identify potential risk factors for the development of such a complication. All the patients had Crohn's disease, and the majority of them were women (19/23; 82.6%). All cases occurred during therapy with anti-TNF agents [14/23 (61%) patients were treated with adalimumab and 9/23 (39%) patients were treated with infliximab]. The therapeutic approach directed at maintaining/holding the undergoing biologic therapy is still uncertain. Further studies are needed to determine the most appropriate treatment choice toward ongoing biologic therapy. Copyright (C) 2021 Wolters Kluwer Health, Inc. All rights reserved
Respiratory Tract Infections in Inflammatory Bowel Disease Patients Taking Vedolizumab: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
No full textThe ongoing COVID-19 pandemic has raised concerns about the risk of SARS-CoV-2 infection in patients with Crohn's disease (CD) and patients with ulcerative colitis (UC) taking immunosuppressants or biologics. We conducted a systematic review and meta-analysis to assess the risk of respiratory infections in patients with inflammatory bowel disease (IBD) treated with vedolizumab. We searched PubMed, EMBASE and Scopus to identify randomized controlled trials (RCT) comparing vedolizumab to placebo in patients with IBD. Outcomes were the rate of respiratory tract infections (RTI), upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) among patients receiving vedolizumab as compared with placebo. Pooled rates were reported as Odds Ratios (OR) with 95% Confidence Interval (CI). Eight RCT involving 3,287 patients (1873 CD and 1415 UC) were analyzed; 2,493 patients received vedolizumab and 794 received placebo. The rates of RTI and URTI were statistically higher in vedolizumab-treated patients compared to placebo [OR = 1.63; 95% CI (1.07-2.49); OR = 1.64 95% CI (1.07-2.53) respectively]. UC patients, but not CD patients, receiving vedolizumab had a higher risk to develop RTI and URTI [OR = 1.98; 95% CI (1.41-2.77); OR = 2.02; 95% CI (1.42-2.87)] compared to placebo-treated patients. The number of LRTI was small in both treatment groups. Data confirm the good safety profile of vedolizumab even though RTI were more frequent in patients receiving vedolizumab and the risk of URTIs was significantly higher in patients with UC
Oligonucleotide-Based Therapies for Inflammatory Bowel Disease
No full textthe growing understanding of the immunopathogenesis of inflammatory bowel diseases (IBDs) has contributed to the identification of new targets whose expression/activity can be modulated for therapeutic purposes. several approaches have been employed to develop selective pharmaceutical compounds; among these, antisense oligonucleotides (ASOs) or synthetic oligonucleotides represent a valid option for inhibiting or enhancing, respectively, the expression/function of molecules that have been implicated in the control of IBD-related inflammation. In this context, data have been accumulated for the following compounds: alicaforsen, an ASO targeting intercellular adhesion molecule-1, a transmembrane glycoprotein that regulates rolling and adhesion of leukocytes to inflamed intestine; DIMS0150 and BL-7040, two oligonucleotides that enhance toll-like receptor-9 activity; mongersen, an ASO that inhibits smad7, thereby restoring transforming growth factor-beta 1/Smad-associated signaling; STNM01, a double-stranded RNA oligonucleotide silencing carbohydrate sulfotransferase, an enzyme involved in fibrogenic processes, and hgd40, a specific DNAzyme inhibiting expression of the transcription factor GATA3. In this article, we review the rationale and the available data relative to the use of these agents in IBD. although pre-clinical and phase II trials in IBD support the use of oligonucleotide-based therapies for treating the pathogenic process occurring in the gut of patients with these disorders, further work is needed to establish whether and which patients can benefit from specific ASOs and identify biomarkers that could help optimize treatment
Niclosamide enema for active distal ulcerative colitis: a phase I, open-label study
No full textIn patients with distal ulcerative colitis, rectally administered drugs have the advantage of acting directly on the site of inflammation with limited systemic exposure. In this phase 1, open-label, single-arm clinical trial, niclosamide enema proved to be safe and effective in treating mild-to-moderate, distal ulcerative colitis. background oral and rectal formulations of 5-aminosalicylic acid are the first-line therapy for mild-to-moderate, distal ulcerative colitis (UC), but such a treatment is not effective in one-third of patients. niclosamide is a small molecule, developed and approved as an orally administered drug to treat helminthic infections, with an excellent safety profile. preclinical work showed that niclosamide is an anti-inflammatory agent, thereby providing the rationale to explore its safety and efficacy in patients with UC. this phase 1, open-label trial was aimed at assessing the safety of niclosamide formulated as an enema in patients with mild-to-moderate, distal UC, who relapsed on maintenance therapy with oral and/or rectal 5-aminosalicylic acid. methods seventeen patients with active UC received niclosamide enema (150 mg/60 mL) twice a day for 6 weeks. the primary endpoint was the safety of niclosamide treatment. secondary endpoints included clinical remission and improvements in endoscopic mayo/histologic scores. endoscopic remission percentages exclude participants meeting criteria at baseline for endoscopic remission. results niclosamide was well tolerated by all 17 patients that were enrolled and treated. no serious adverse event was registered. fifteen mild adverse events were registered in 6 patients and considered to be unrelated to the treatment. clinical remission was achieved in 10 (59%) of 17 patients. Improvements of endoscopic Mayo score and histologic geboes score were seen in 7 (58%) of 12 and 7 (41.2%) of 17 patients, respectively. conclusions niclosamide enema treatment is safe and well tolerated. niclosamide improves clinical symptoms and endoscopic/histologic signs of UC; however, appropriately designed placebo-controlled clinical trials are required to confirm efficacy
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