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Introduction:Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). Surveillance colonoscopy is currently recommended for patients with long-standing extensive colitis for reducing CRC risk. Chemoprevention is an attractive complementary strategy. Areas covered:Inflammation is a major determinant of CRC risk and is potentially modifiable. Reducing inflammation is supposed to reduce CRC risk. Several medications have been evaluated in this setting: 5-ASA, thiopurines, anti-TNFα agents and ursodeoxycholic acid (UCDA) in patients with associated primary sclerosing cholangitis (PSC). This review offers a critical evaluation of current evidence of the potential chemopreventive effect of such medications. Expert commentary:No randomized controlled trials have been performed and the available evidence come from observational studies. Although biological plausibility supports a chemopreventive role of the aforementioned agents, the overall evidence of efficacy is weak because of several methodological limitations of the studies. Indirect epidemiological evidence, biologic plausibility and results of meta-analyses reasonably support a potential chemopreventive effect of 5-ASA. Available evidence does not support a specific chemopreventive effect of purine analogues and anti-TNFα medications, despite their efficacy in the management of inflammatory bowel disease. Data addressing UDCA and folate supplementation are inconclusive. Limited data are available for statins. [ABSTRACT FROM PUBLISHER]

Introduction: Methotrexate is commonly used in rheumatoid arthritis but randomised controlled trials demonstrated its efficacy also in Crohn’s disease. Methotrexate, although marginally used in clinical practice, is considered an appropriate immunomodulator particularly in patients refractory or intolerant to thiopurines. Areas covered: A literature search using ‘methotrexate’, ‘Crohn’s disease’ and ‘Inflammatory Bowel Disease’ as key words, identified randomised controlled trials, meta-analyses and observational studies. The aim of this review is to summarise and critically discuss the available evidence concerning the efficacy and safety of methotrexate in the treatment of Crohn’s disease. Expert commentary: Methotrexate is effective in inducing and maintaining remission in steroid-dependent CD at a dose of 25 mg/week and 15 mg/week, respectively. Data from observational studies suggest that methotrexate may be as efficacious as thiopurines with a similar safety profile. In specific clinical settings, (patients with a history of malignancy or young Epstein-Barr Virus–seronegative patients), methotrexate compete favourably with thiopurines. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Background & Aims: Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis factor (TNF) inhibitors in these patients. Methods: We collected data from patients with IBD treated with infliximab (n = 2475) and adalimumab (n = 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn''s disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 years old or younger who were treated with both biologics and 190 patients older than 65 years who were treated with other drugs. The primary end points were severe infection, cancer, or death. Results: Among patients more than 65 years old who received infliximab and adalimumab, 11% developed severe infections, 3% developed neoplasms, and 10% died. No variable was associated with severe infection or death. Among control patients more than 65 years old, 0.5% developed severe infections, 2% developed cancer, and 2% died. Among control patients less than 65 years old, 2.6% developed severe infections, none developed tumors, and 1% died. Conclusions: Patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age that did not receive these therapeutics. The effects of anti-TNF agents in older patients with IBD should be more thoroughly investigated, because these patients have higher mortality related to hospitalization than younger patients. [Copyright &y& Elsevier]

The treatment of moderate-to-severe steroid-dependent Crohn's disease has been a challenging issue for the gastroenterologist. Until to 10 years ago, immunosuppressors, mainly azathioprine or 6-mercaptopurine, were the best possible treatments available, and remission rates ranged from 30 to 60% according to the results of open studies and controlled trials. Recently, infliximab has been shown to be effective in steroid-dependent patients and, combined with azathioprine, it has been shown to increase 1-year remission rates. A recent large randomized controlled trial comparing infliximab, azathioprine and infliximab plus azathioprine demonstrated that the combination of infliximab plus azathioprine is the most suitable treatment for obtaining steroid-free remission after 26 weeks: steriod-free remission was obtained in 56% of the patients in the infliximab plus azathioprine group versus 44% of patients receiving infliximab alone and 30% of patients receiving azathioprine alone. No relevant differences were observed in the rate of side effects in the three groups of treatments. In this article, the results of this trial are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Complementary and alternative medicines (CAM) are being used increasingly by patients with Crohn''s disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and usage of CAM in different geographical areas of Italy and possible predictors of their use. Methods and materials: A structured questionnaire, administered to outpatients, attending 8 general hospitals and 9 tertiary referral centres, was completed by 2011 patients (909 CD, 1087 UC and 15 indeterminate colitis). 583 patients lived in the North, 659 in Central Italy and 769 in the South. Results: CAM users were 475 (23.6%) with no regional differences in their distribution. Usage correlated significantly with female gender (p =0.030), higher education (p =0.021), hospitalization rates (p =0.000), extra-intestinal complications (p =0.000), non-adherence to conventional treatments (p =0.054), adverse reactions to conventional treatments (p =0.000), and active disease (p =0.007); 5-ASA usage was associated with a more limited use of CAM (p =0.005). Dietary changes or supplements and prayer were significantly more frequently reported in South, while Northern Italian patients more frequently used homeopathy, herbal medicines and physical exercises. Patients in Central Italy adopted an intermediate behavior. CAM use ameliorated the patient''s general well-being according to two thirds of the users. Costs were higher for Northern patients than in Central or Southern Italy. Conclusion: One in four IBD patients in Italy use CAM. More money is spent on CAM in Northern Italy. Regional differences emerged as regards the type of CAM but not in terms of disease features, frequency of and reasons for CAM use, or perceived effects. [Copyright &y& Elsevier]

INTRODUCTION: Corticosteroids are the gold standard in the treatment of moderate to severe Crohn's disease but are often associated with severe and potentially dangerous side effects. Despite an initial clinical response many patients become steroid dependent or require further steroid courses in the long term. The aim of the present study was to assess the probability of the need for further steroid treatment in Crohn's disease patients following steroid-induced remission and to establish if clinical variables can predict further steroid needs. PATIENTS AND All METHODS: patients at their first steroid course and with corticosteroid-induced remission, defined as a Crohn's Disease Activity Index (CDAI) <150, 4 wk after steroid weaning, were studied and observed at follow-up for 12 months. The main outcome was clinical relapse requiring further steroid treatment. Statistical analysis was performed using the Kaplan-Meier method and multivariable Cox proportional hazard regression model taking into consideration gender, age at diagnosis, disease location and behavior, smoking habits, CDAI score before steroid treatment, and C reactive protein values at steroid weaning, as covariates. RESULTS: A total of 77 patients with steroid-induced remission were included. One-year follow-up was available in 75 of the 77 patients (97.4%). During follow-up 49 of 75 patients (65.3%) maintained remission or presented mild relapse not requiring steroids while 26 of 75 patients (34.6%) had moderate to severe relapse requiring further steroid treatment. The cumulative probability of a course free from steroids was 93.3%, 82.6%, 78.6%, and 66.6% at 3, 6, 9, and 12 months, respectively. At multivariate analysis, increased C reactive protein at steroid weaning and penetrating complications were independent risk factors for further steroid requirement (OR 5.57, 95% CI 1.20–25.91, P= 0.001 and OR 4.20, 95% CI 1.76–10.04, P= 0.005, respectively). CONCLUSION: Despite an initial clinical response and successful steroid tapering, 35% of patients required further steroid treatment within 1 yr. An increased C reactive protein value, at steroid weaning, despite clinical remission, and penetrating complications may predict further steroid requirement in already steroid responsive patients. [ABSTRACT FROM AUTHOR]

In the last years mucosal healing has emerged as an important therapeutic goal for patients with inflammatory bowel disease. Growing evidence suggests that mucosal healing can improve patient outcomes and, potentially, can alter the natural course of the disease by inducing sustained clinical remission and reducing hospitalizations and surgery. However several questions remain to be answered. A validated definition of mucosal healing is still lacking and the effect size of different drugs is difficult to assess because of different definitions, different study design, and different timing of endoscopic evaluation. The evidence that mucosal healing has a high positive predictive value for long-term good clinical outcome is still limited and, therefore, mucosal healing remains a weak surrogate end point of disease course. Future studies are needed to develop a standardized definition of mucosal healing and to prospectively assess the impact of mucosal healing on long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-TNFα 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-TNFα 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. [ABSTRACT FROM AUTHOR]