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Introduction: Crohn`s disease (CD) and ulcerative colitis (UC) are the two main subtypes of inflammatory bowel disease (IBD). Although the etiology of both diseases still remains unsolved, we have seen significant progress concerning new therapies for both diseases within the last years [1,2]. Especially novel therapeutics, such as anti-TNF agents are promising in the therapy of IBD. Unfortunately, only about 2/3 of the patients show initial response to the new therapies. A cross analysis indicates a loss of infliximab response with a mean of 37% with an annual risk for loss of response about 13% per patient-year [3]. Due to this, further and new therapeutic strategies are still needed.
In refractory cases of IBD, hematopoietic stem cell transplantation has successfully been used in a rare number of patients. However, only a limited subgroup of patients seems eligible for this therapy so far due to a quite risky therapy with potential huge side effects [4,5].

Introduction: Acute severe colitis (ASC) is a potentially life-threatening condition with estimated rates of colectomy of up to 40%(1). Patients presenting with ASC should be admitted to the hospital and started on intravenous (iv) corticosteroids(2). However, around 15 to 57% of patients will be refractory to this therapy (3); in those who fail to respond within 3–5 days, or who present with frank deterioration at any earlier point, rescue therapy with either ciclosporin 2 mg/kg or infliximab (IFX) 5 mg/kg is generally considered as an alternative to surgery.
The efficacy of ciclosporin in the treatment of ASC was demonstrated more than 15 years ago. In a small randomised placebo-controlled trial, 9 out of 11 patients treated with 4 mg/kg ciclosporin has a response compared to none of the 9 placebo-treated patients(4). Later on, in a dose-finding trial, ciclosporin doses of 2 mg/kg and 4 mg/kg per day were found to be equivalent (5). IFX was shown to be an effective salvage therapy in patients with steroid-refractory ASC in a pivotal randomised controlled study conducted by Jarnerot et al. In this trial, 67% (14/21) of patients in the placebo-treated group required colectomy by 3 months as compared to 29% (7/24) of those treated with a single dose of infliximab 5 mg/kg (6).
The decision on whether to select ciclosporin or IFX in the setting of steroid-refractory ASC, in the absence of a specific contra-indication to each particular drug, usually depends on centre and physician’s personal experience and patient’s preference. Arguments supporting IFX are its ease of use and better safety profile. Besides that, because patients previously failing azathioprine are more prone to colectomy following initial response to ciclosporin(7), previous thiopurines-failures may be considered better candidates to IFX. In the other hand, arguments favouring ciclosporin are its reported high and rapid response rates, and its short half-life. Ciclosporin clears more rapidly from the circulation than IFX, and therefore some physicians may prefer its use in patients where colectomy is felt to be more imminent, to prevent septic complications.
So far no clear guidance for the choice between both agents was possible due to the lack of comparative trials. In this recently published manuscript, Laharie et al. present the results of the first trial comparing ciclosporin and IFX for ASC.

Introduction: Ulcerative Colitis (UC) is an idiopathic chronic inflammatory disease of the colon with episodes of relapses between remissions. Conventional pharmacological treatment relies on aminosalicylates and immunomodulators (thiopurines), with or without corticosteroids. However, up to 16% of patients do not respond to optimal treatment with thiopurines [1]. The ACT-1 and ACT-2 have demonstrated efficacy of infliximab (IFX) for both induction and maintenance of remission in corticosteroid and/or thiopurine refractory moderate to severe UC. However, respectively 51% and 42% of patients that received IFX in the ACT-1 and ACT-2 trial also received thiopurines. It remains unclear whether the efficacy of thiopurine and IFX in combination is superior to either alone in the treatment of moderate to severe UC [2].

Introduction: Therapy with immunomodulators has no clear affect on disease progression and rate of surgery in Crohn’s disease (CD), although efficiency has been demonstrated long time ago [1,2]. In children the early treatment with azathioprine resulted in reduced need for prednisolone and lower relapse rates [3,4].
The reason for this lack of affect on disease progression might be a delayed prescription of the drug, therefore the aim of the presented study was to evaluate the concept of early azathioprine therapy in adult patients with Crohn’s disease.

Introduction: In terms of the number of investigations into the use of biologics to induce and maintain clinical remission, Ulcerative Colitis (UC) has been a ‘neglected cousin’ to Crohn’s Disease. ACT-1 and ACT-2 [1] assessed the efficacy and safety of infliximab versus conventional treatment in patients with moderately to severely active UC. UC patients in the infliximab arm were more likely to achieve clinical response, remission or mucosal healing at weeks 8, 30 and 54 than those receiving conventional treatment. In addition, maintenance infliximab reduced the risk of colectomy in this UC patient population [2]. Colombel et al. have undertaken a subgroup efficacy analysis of ACT-1 and ACT-2 to evaluate a possible correlation between endoscopy subscores at 8 weeks of treatment with infliximab or placebo and subsequent long-term clinical outcomes at week 54. The outcomes assessed included colectomy rates, commercial infliximab use, symptomatic remission (Mayo Stool Frequency of 0 or 1 and a rectal bleeding subscore of 0), corticosteroid-free symptomatic remission, corticosteroid-free status and sustained mucosal healing. In effect they asked the question: Does the patient’s response at 8 weeks predict what will happen in a year’s time?
ACT-1 and ACT-2 [1] enrolled UC patients with moderately to severely active colitis despite conventional treatment and placed them into one of three arms: placebo, infliximab (5 mg/kg) and infliximab (10 mg/kg). Colombel et al. separated each of these arms into their Mayo endoscopy subscores at week 8.

Introduction: The aetiology of Inflammatory Bowel Disease (IBD) is still incompletely understood. Epidemiological observations may be helpful in identifying the true causative factors of this disease. Historically, the prevalence and incidence of IBD have been higher in developed countries, with a decreasing gradient from North to South gradient and, to a lesser degree, from West to East [1]. However, more recent data demonstrate changes in demography as countries become more developed and immigration increases [2]. Several hypotheses have been put forward to explain these changing demographics, but direct experimental evidence is lacking in most cases [2,3]. Racial and ethnic relations in different populations and immigration studies offer interesting data which reflect a complex interplay between genetic, environmental and behavioural factors [1–3]. Diet, alterations in the bowel microflora, smoking habits and the influence of hormonal status and drugs are viewed as contributing factors in the manifestation of the disease [1,3]. However, these factors may differ for Western and Eastern European countries. In fact, some articles report that the Western-Eastern discrepancy can be merely attributed to a difference in life styles [1].
Understanding the discrepancies between data from populations with different genetic backgrounds and environmental factors may reveal fundamental aspects of IBD pathogenesis [3].
Recent studies from Eastern Europe have reported acute increases in the incidence of IBD in some countries, comparable with Western European incidence rates, whereas in other Eastern European centres, IBD incidence has not been investigated [4,5]. It remains unknown whether these changes represent true increases in IBD incidence, rising awareness of the disease or differences in diagnostic practices.

In the past few years the armamentarium of drugs used to treat Inflammatory Bowel Disease (IBD) has accelerated, with the emergence of new therapies targeting differing immune pathways (ustekinumab and tofacitinib) and lymphocyte trafficking (vedolizumab). Furthermore, a number of promising new drugs are on the horizon (JAK-1 inhibitors, IL23p19 antibodies and S1P inhibitors) [1, 2]. However, as the choice of drugs expands, so the uncertainty over which drug should be selected by the clinician also increases. Drug selection may be determined by a number of factors such as cost, mechanism of delivery (e.g. oral, intravenous or subcutaneous), presence of co-morbidities (such as malignancy or multiple sclerosis) and presence of extraintestinal manifestations. However, no drug is effective in all patients, with between 10% and 40% of patients suffering from primary and secondary loss of response [3–5].

Perianal fistulising Crohn’s Disease is a challenging phenotype affecting more than 20% of patients diagnosed with Crohn’s Disease. It is associated with debilitating symptoms and significant morbidity, with subsequent reduced quality of life and increased disease-related work disability.

Currently treatment remains challenging, incorporating surgical and medical management; the latter is driven largely by biologic agents, specifically anti-tumour necrosis factor (TNF) agents such as adalimumab (ADA) and infliximab (IFX). Whilst ADA and IFX have proven efficacy in inducing and maintaining fistula healing and closure, a significant proportion of patients fail to respond or lose response over time. Increasing evidence suggests that this is in part due to sub-therapeutic drug levels, with or without the presence of antibodies to anti-TNF agents (ATA), with higher target drug levels required for fistula healing compared to mucosal healing in Crohn’s Disease. However, data evaluating the correlation between anti-TNF levels and perianal fistula outcomes, particularly with ADA, remain limited.

The aim of this study was to assess the association between anti-TNF levels and perianal fistula healing and closure with maintenance ADA and IFX therapy.

The anti-TNF monoclonal antibody infliximab offers an effective treatment for patients with Inflammatory Bowel Disease (IBD) refractory to conventional immunomodulator therapies. Successful biologic therapy can lead to clinical and endoscopic remission as well as reduced hospitalisation and requirement for surgery [1].

Unfortunately, as a large protein and chimeric antibody, infliximab is immunogenic and this frequently leads to formation of anti-drug antibodies (ADA), with subsequent secondary loss of response (LOR), drug discontinuation and adverse reactions [2]. Identifying patients at increased risk of developing antibodies prior to treatment may establish which individuals require closer drug level monitoring, concomitant immunomodulator therapy and observation for adverse events.

Previous work by Sazonovs et al. identified the first genetic locus to be robustly associated with immunogenicity to anti-TNF therapies [3]. The HLADQA1*05 allele variant rs2097432, carried by approximately 40% of Europeans, significantly increased the rate of formation of infliximab ADA. In the study reviewed here, Wilson et al. aimed to independently identify whether presence of the variant allele was associated with increased risk of ADA formation, LOR, drug discontinuation and adverse events.

No increased risk of SBA or CRC was demonstrated in this study despite the long follow-up and the large number of patients. Young age at diagnosis, male gender and stricturing disease at diagnosis were identified as possible risk factors. This suggests that young males with CD should be monitored more carefully from the start, independent of disease location. Studies of colitis in mice as well as clinical trials have suggested that helminth infection can prevent and/or treat IBD.

This article by Broadhurst et al. describes the disease course of a 35-year-old patient diagnosed with severe UC in 2003, refractory to medical treatment. In early 2004, he chose to infect himself with T. trichiura eggs, followed by a completely symptom-free period. In 2008, after deterioration of disease, he chose again to infect himself with T. trichiura eggs, followed by a progressive improvement of the symptoms and histopathological findings. During the whole disease course, the cellular and molecular portrait of changes in the intestinal mucosa was followed with special attention to IL-22, which promotes wound healing and proliferation and Th17 cells.

Introduction: High geographical variability of IBD has been observed [1, 2]. In developed countries, incidence of IBD has markedly increased over 50 years suggesting an influence of environmental factors associated with industrialization and urbanization of societies [3, 4]. In developing countries, trends of incidence of IBD are lacking. It seems however that IBD is going to emerge in countries of previously low or rare disease prevalence. This has been observed also in Asia, as regards to previous hospital-based studies showing an increased number of treated patients. It becomes therefore important to perform further epidemiological studies in countries were diseases are emerging for different reasons. The emergence of IBD in developing countries or regions where IBD prevalence was low or inexistent suggests that the development of IBD may be influenced by changing environmental risk factors. Collecting prospective information on environmental and “modern” lifestyle exposure factors over time in developing countries undergoing rapid socioeconomic changes and westernization would thus provide a unique opportunity to study the role of such risk factors on the etiology of IBD. The conjunction of potential increase of IBD in developing countries with wide background population also calls for anticipation in terms of planning and organization of healthcare resources.

Reflecting the programme of the 2011 ECCO Congress in Dublin there are different lines of current understanding and research. The classical and probably most established investigation line is the role of the adaptive immune system including the role of Th-1 driven inflammation. The more recent but already very dominant area of interest is the role of the microbiota, which is generally accepted to trigger the inflammation in both Crohn’s Disease and Ulcerative Colitis. Another translational research driven achievement of the past years is the acknowledgment of different clinical phenotypes and disease locations, most importantly the understanding that ileal inflammation is likely due to different factors than inflammation in the colon. The newest and – by some – still controversially discussed field is the understanding of host antimicrobial defense and especially the understanding that – at least – different types of IBD are caused by a barrier problem. In the lines of a barrier problem, different mechanisms including NOD2 mutations, stem cell differentiation WNT signaling defects, Autophagy as well as endosomal stress pinpoint to an important role of the small intestinal crypt – epithelial Paneth cell, especially in case of small intestinal disease involvement.

For some time it has been recognised that alterations in the gut bacteria are associated with Inflammatory Bowel Disease. However, it is unclear which is the chicken and which is the egg – does this “dysbiosis” arise due to genetic differences in affected individuals or because of the inflammatory conditions present in the intestine, or is it causative and a prerequisite for disease to develop, and if so how?

Low bone mineral density (BMD) is both prevalent and frequently unrecognised in patients with inflammatory bowel disease (IBD). With osteoporosis occurring at a rate of 10–14% in the IBD population already at a median age of 33–41 years, low BMD can well be considered an extra intestinal manifestation of IBD. Despite this, and the availability of guidelines from the American Gastroenterological Association and the American College of Gastroenterology, testing rates for osteoporosis have been reported to be low in IBD patients [1, 2].

Introduction: The IL-12 family of cytokines plays an important role in the pathogenesis of IBD. It consists of pro-inflammatory cytokines enhancing inflammation by induction of Th1/ Th17 responses, like IL-12 and IL-23, but also of members with an immunosuppressive function, like IL-27 and IL-35.
Interestingly, the IL-12 family consists of heterodimeric cytokines composed of two subunits, some of which are shared amongst family members. IL-27 is composed of EBI3 (Epstein-Barr virus-induced gene 3) and the IL-27p28 subunit, whereas IL-35 is composed of EBI3 and IL-12p35. In contrast to the well-defined function of IL-12 and IL-23 in IBD, the function of IL-27 and IL-35 is still unclear. In particular, functional studies of IL-35 are hampered by the current limitations in our ability to detect it and the fact that knockout of the EBI3 subunit will also affect IL-27 expression and knock-out of the IL-12p35 unit will also affect IL-12 expression.
Wirtz et al. elegantly circumvented this problem by using mice deficient in both EBI3 (lacking both IL-27 and IL-35) and IL-27p28 (lacking only IL-27) to gain insight into the role of IL-35. The differences between the EBI3 and IL-27p28 deficiency were studied in a variety of established mouse colitis models, using state of the art imaging tools, i.e. murine endoscopy and bioluminescence, to assess colonic inflammation in vivo.

The positioning of medical therapies in the management of Crohn’s Disease (CD) continues to be debated [1] whilst surgery is reserved for cases with disease complications or failure of medical therapy.  The LIR!C trial [2] provided evidence for  surgical resection as an alternative to infliximab (IFX) in the management of localised terminal ileitis, a common presentation of CD [3].

Briefly, the LIR!C trial reported quality of life scores (IBDQ) among 143 adult patients with terminal ileitis (<40 cm) who underwent randomisation to IFX induction/maintenance or ileocaecal resection. Patients were recruited from 29 secondary and tertiary Dutch and British centres. Exclusion criteria included non-inflammatory disease, prestenotic dilatation, abscess and previous surgery. Inclusion criteria included failing at least three months of conventional therapy [immunomodulator (IM) and/or corticosteroid (CS)] [2]