The use of oral corticosteroids in inflammatory bowel diseases in Italy: An IG-IBD survey.

AIM: To evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). MATERIAL AND METHODS: All members of the Italian Group for Inflammatory Bowel Disease (IG-IBD) were invited to fill in a web-based questionnaire. RESULTS: 131/448 (29.2%) members completed the survey. In mild-to-moderate UC and CD relapses, low-bioavailability steroids (LBS) are first-line therapy for 37% and 42% of clinicians, respectively. In case of failure, immediate step-up to biologics or immunosuppressants is considered by 23% and 29%. Regarding conventional corticosteroids (CCS), a fixed starting dose is prescribed by 50%, and a weight-based dose by 22%. Tapering is started after 7-10days by 41% and after 14days by 32%. The preferred tapering schedule is 5mg/week. In case of CCS failure, 47% switch to parenteral steroids before considering shifting to different drug classes. In case of symptoms recurrence during tapering, 14% re-increase the dose and try tapering again. Before prescribing steroids, 72% do not prescribe any specific evaluation whereas during treatment some evaluation is performed by 85%. Vitamin D and calcium supplements are routinely prescribed along with steroids by 38%. CONCLUSIONS: Several discrepancies and some deviation from the available guidelines were recorded among Italian gastroenterologists regarding corticosteroids use in IBD patients.

The problem of adherence to therapy in ulcerative colitis and the potential utility of multi-matrix system (MMX) technology.

INTRODUCTION: Ulcerative colitis (uc) is a chronic condition and for the vast majority of patients, life-long treatment is required. low adherence to therapy is an emerging issue. since low adherence is associated with poor clinical outcomes and increased costs, it is becoming crucial to identify strategies in order to improve it. Areas covered: We performed literature searches in PubMed using the terms 'adherence', 'mesalamine', 'budesonide MMX', 'MMX technology' in combination with 'ulcerative colitis'. Firstly, we present the key-concepts of therapy for UC and discuss the problem of the adherence and how to measure it. Then, we provide data on the extent of the problem and the causes and consequences from clinical and economic point of views. Finally, we focus on treatment-related variables associated with non-adherence and treatment-related strategies to improve adherence, paying particular attention to Multi Matrix system (MMX) technology applied to mesalazine and budesonide. Expert commentary: The pharmaceutical industry and scientific community are making efforts to simplify treatments for UC. MMX technology, which allows a reduction in the number of pills to be taken and daily administrations, may facilitate adherence to treatment and carry further clinical benefits.

Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first presentation to gastroenterology services in adults aged 16-50 years.

BACKGROUND: Distinguishing inflammatory bowel disease (IBD) from functional gastrointestinal (GI) disease remains an important issue for gastroenterologists and primary care physicians, and may be difficult on the basis of symptoms alone. Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but not cancer. AIM: This large retrospective study aimed to determine the most effective use of FC in patients aged 16-50 presenting with GI symptoms. METHODS: FC results were obtained for patients presenting to the GI clinics in Edinburgh between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing FCs from >16,000 patients. Case notes were interrogated to identify demographics, subsequent investigations and diagnoses. RESULTS: 895 patients were included in the main analysis, 65% female and with a median age of 33 years. 10.2% were diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI tract and 63.2% had functional GI disease. Median FC in these three groups were 1251, 50 and 20 µg/g (p < 0.0001). On ROC analysis, the AUC for FC as a predictor of IBD vs. functional disease was 0.97. Using a threshold of ≥ 50 µg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99. Combined with alarm symptoms, the sensitivity was 1.00. CONCLUSIONS: Implementation of FC in the initial diagnostic workup of young patients with GI symptoms, particularly those without alarm symptoms, is highly accurate in the exclusion of IBD, and can provide reassurance to patients and physicians.

Low bioavailability steroids in inflammatory bowel disease: an old chestnut or a whole new ballgame?

At present, therapy of inflammatory bowel disease is still far from being fully satisfactory; old drugs like steroids, for instance, still represent a cornerstone in the treatment of active disease despite their associated important side effects and incomplete clinical efficacy. In the last years, new therapeutic strategies have been suggested in order to avoid or at least limit steroids use and in this direction the so-called low bioavailability steroids appeared to be a promising therapeutic weapon; however, some grey areas about their real utility and manner of use still remain. The aim of this review is to evaluate the available evidence about the use of oral budesonide and beclomethasone dipropionate in inflammatory bowel disease, to critically assess their current position in the therapeutic algorithm of these diseases and to give simple and practical indications for their use in every-day clinical practice.

Mucosal healing in inflammatory bowel disease: treatment efficacy and predictive factors.

In recent years mucosal healing has emerged as an important therapeutic goal for patients with inflammatory bowel disease. Growing evidence suggests that achieving mucosal healing can improve patient outcomes and, potentially, alter the course of the disease. Drugs currently used in the management of inflammatory bowel disease are potentially able of inducing and maintaining mucosal healing, but the effect size is difficult to assess because of different definitions of mucosal healing, differences in study designs, and timing of endoscopic evaluation. Mucosal healing has been studied extensively in the biologic era. Data available from different sources, such as controlled trials and observational studies, show that anti-TNFα therapies can induce rapid and sustained mucosal healing in a variable percentage of patients with Crohn's disease and ulcerative colits. No controlled study has been designed to identify possible predictors of mucosal healing. Some clinical characteristics such as extensive disease, young age at diagnosis, and smoking status may be predictive of a more aggressive clinical course and, presumably, of a reduced clinical and endoscopic response to therapy. Changes and normalization of C-reactive protein and faecal calprotectin may be useful tools to predict outcomes, guide the timing for endoscopic evaluation and, possibly, reduce the need of endoscopic evaluation in assessing mucosal healing.

[Prevention of post-operative recurrence in Crohn's disease: a critical review of randomized controlled trials and meta-analyses of different therapeutic strategies]. / La prevenzione della recidiva post-chirurgica nella malattia di Crohn. Revisione degli studi clinici controllati e delle meta-analisi sulle strategie terapeutiche.

Surgery is an almost inevitable event in Crohn's disease but is not curative; post-operative recurrence follows a sequential and predictable course. Prevention of post-operative recurrence in Crohn's disease is therefore a relevant problem in the management of the disease. Several drugs have been evaluated to decrease the risk of recurrence: these include mesalazine, antibiotics, probiotics, budesonide, thiopurines and biologic agents. This review focuses on the randomised controlled trials and meta-analyses addressing different drugs and strategies for preventing post-operative recurrence in Crohn's disease.

Low bioavailability and traditional systemic steroids in IBD: can the former take over the latter?

Systemic corticosteroids have been used to treat active inflammatory bowel disease for over 50 years by virtue of their unquestionable efficacy in inducing clinical remission rapidly in the vast majority of patients. Nevertheless, traditional corticosteroids are associated to a plethora of potentially serious side effects due to their systemic metabolism; for this reason, interest has lately been growing in newer steroid compounds characterized by a high topical anti-inflammatory activity and a low systemic bioavailability. These compounds, namely budesonide and beclomethasone dipropionate--regarding the treatment of inflammatory bowel disease--can be administered orally and thanks to sophisticated delivery systems are conveyed specifically to the inflamed gut mucosa where they exert their anti-inflammatory action. After intestinal absorption, these drugs are promptly and efficiently inactivated by the liver, so that only inactive molecules reach the systemic circulation. This review revises the main clinical trials, meta-analyses and observational studies conducted on traditional and newer steroids, and critically interprets the main results achieved by these studies.

Randomized controlled trials in prevention of postsurgical recurrence in Crohn's disease.

Most patients with Crohn's disease will require surgery during the course of their disease. However, surgery is not curative and post-operative recurrence is quite inexorable. One year after resection up to 80% of patients have new lesions at the neo-terminal ileum and after 10 years approximately 50% of patients will experience recurrence of symptoms and 35% will need further surgery. Prevention of post-operative recurrence has, therefore, a central role in the management of Crohn's Disease. Several drugs have been evaluated to decrease the risk of both endoscopic and clinical recurrence but the overall results are largely not impressive. Among the different drugs evaluated, mesalazine, antibiotics (metronidazole and ornidazole), thiopurines and anti-TNFα antibodies have been shown to be effective whereas budesonide, probiotics and interleukin 10 are not effective. This review focuses on the actual evidence on the prevention of postoperative recurrence: randomised controlled trials and meta-analyses are critically reviewed and discussed with particular attention to the methodological aspects.

Early treatment in Crohn's disease: do we have enough evidence to reverse the therapeutic pyramid?

Current guidelines on the medical therapy of Crohn's disease recommend a step-up strategy consisting of a progressive intensification of treatment as the disease severity increases. In the last fifteen years, the introduction of biologic therapies, particularly anti-TNFα antibodies, has offered new therapeutic opportunities. The efficacy of anti-TNF-alpha therapy for inducing and maintaining clinical response or remission in moderate to severe Crohn's disease has been extensively evaluated in randomised controlled trials and meta-analyses. Moreover, anti-TNF-alpha therapy can induce mucosal healing and this property may be potentially disease-modifying. Consequently, an early introduction of biologics and/or immunomodulators (top-down strategy) in newly diagnosed Crohn's disease has been advocated. This paper will review the evidence in favour and against this approach to Crohn's disease therapy, discuss which patients are potential candidates to early aggressive treatment, and how a conventional step-up approach can be optimized. The conclusion is that an indiscriminate top-down approach does not seem to be appropriate for all patients with moderate to severe Crohn's disease.

Oral beclomethasone dipropionate: a critical review of its use in the management of ulcerative colitis and Crohn's disease.

Crohn's disease and ulcerative colitis are inflammatory bowel diseases characterised by a chronic relapsing course. Corticosteroids represent the mainstay of medical treatment of inflammatory bowel disease for the induction of remission. Despite the high efficacy of systemic steroids, their use is limited by the high incidence of potentially serious adverse effects. The topically acting steroids are synthetic compounds characterised by high anti-inflammatory activity and low systemic effects by virtue of efficient first-pass hepatic inactivation. Budesonide and Beclomethasone Dipropionate are the two most studied topically acting steroids in inflammatory bowel disease. Oral Budesonide has been extensively studied in the treatment of mild to moderate ileo-caecal Crohn's disease but few data are available concerning oral Beclomethasone Dipropionate. This review focuses on the available evidence of efficacy and safety of oral Beclomethasone Dipropionate in the management of ulcerative colitis and Crohn's disease and a possible role of this steroid in clinical practice is suggested.