This paper is the second in a series of two publications relating to the European Crohn's and Colitis Organisation ECCO evidence-based consensus on the diagnosis and management of Crohn's disease CD ...and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper Gomollon et al JCC 2016.
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Inflammatory bowel disease (IBD) refers to a group of heterogeneous disorders associated with chronic inflammation of the gut, having a high rate of incidence in the world. In the ...present review, we will discuss the link between the short-chain fatty acids, especially butyrate (BT), produced by bacterial fermentation of dietary fiber, and IBD development. Current knowledge supports an anti-inflammatory role for BT and suggests that BT insufficiency may be involved in the pathogenesis of IBD. We will present the molecular mechanisms involved in the anti-inflammatory effect of BT, namely histone deacetylase inhibitor activity, activation of PPARγ and of GPR109A, GPR41 and GPR43 receptors. The histone deacetylase inhibitor activity of BT depends of its absorption by colonocytes. Therefore, BT transporters are also important players in BT-induced anti-inflammatory effect at colonic level. Finally, BT-based future prospects for IBD therapy (modulation of diet (through increased prebiotic (fiber) ingestion) and microbiota (BT-producing probiotic bacteria) supplementation - that can increase the levels of BT in colon - and development of pharmacological BT analogues) will be presented.
Patients with inflammatory bowel disease(IBD)may have an increased risk of venous thrombosis(VTE).PubMed,ISI Web of Knowledge and Scopus were searched to identify studies investigating the risk of ...VTE and the prevalence of acquired and genetic VTE risk factors and prothrombotic abnormalities in IBD.Overall,IBD patients have a two-to fourfold increased risk of VTE compared with healthy controls,with an overall incidence rate of 1%-8%.The majority of studies did not show significant differences in the risk of VTE between Crohn’s disease and ulcerative colitis.Several acquired factors are responsible for the increased risk of VTEin IBD:inflammatory activity,hospitalisation,surgery,pregnancy,disease phenotype(e.g.,fistulising disease,colonic involvement and extensive involvement)and drug therapy(mainly steroids).There is also convincing evidence from basic science and from clinical and epidemiological studies that IBD is associated with several prothrombotic abnormalities,including initiation of the coagulation system,downregulation of natural anticoagulant mechanisms,impairment of fibrinolysis,increased platelet count and reactivity and dysfunction of the endothelium.Classical genetic alterations are not generally found more often in IBD patients than in nonIBD patients,suggesting that genetics does not explain the greater risk of VTE in these patients.IBD VTE may have clinical specificities,namely an earlier first episode of VTE in life,high recurrence rate,decreased efficacy of some drugs in preventing further episodes and poor prognosis.Clinicians should be aware of these risks,and adequate prophylactic actions should be taken in patients who have disease activity,are hospitalised,are submitted to surgery or are undergoing treatment.
Abstract
Background and Aims
Filgotinib is a small molecule that selectively inhibits Janus kinase JAK type 1. It is already approved for the treatment of rheumatoid arthritis and is being evaluated ...for the management of patients with moderate to severe ulcerative colitis UC. The purpose of this review is to provide an overview of the currently available data on filgotinib and to define how to position this new drug in the treatment algorithm of patients with UC.
Methods
The Pubmed, Embase and Scopus databases were searched up to June 25, 2021 in order to identify studies reporting efficacy and safety data of filgotinib in patients with UC.
Results
Data from a phase III study enrolling UC patients with moderate to severe disease show that filgotinib is effective with a reassuring safety profile. Filgotinib treatment is not associated with a greater risk of thrombosis and herpes zoster infections compared to other JAK inhibitors. However, animal studies reported impaired spermatogenesis and histopathological effects on male reproductive organs, making it necessary to deepen this aspect in dedicated human studies.
Conclusions
Filgotinib is an effective and safe drug for treatment of both biologic-naive and biologic-experienced patients with moderate to severe UC and may soon be available.
Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin ...America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD.
Abstract
Currently, the main targets of drug therapy for ulcerative colitis UC are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including ...histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia.
Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn’s and Colitis Organisation ECCO reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible.
We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index RHI or the Nancy index NI. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.
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