Prospective multicenter observational trial on the safety and efficacy of LEVORAG® Emulgel in the treatment of acute and chronic anal fissure.

BACKGROUND: Anal fissure (AF) is a common cause of anal pain with a tendency not to heal spontaneously because of ischemia of the anoderm caused by sphincter spasm. Lateral internal sphincterotomy, while very effective, can cause fecal incontinence and chemical sphincterotomy by application of cream may have discouraging side effects and/or low efficacy. The aim of this prospective multicenter study was to evaluate the safety and effectiveness of a new medical treatment based on Emulgel cream, with emollient, soothing and protective agents, on AF healing. METHODS: Consecutive patients with AF treated in nine coloproctology units during 6 months entered the study on topical treatment with Levorag(®) Emulgel (THD S.p.A Correggio (RE), Italy). Before treatment, they had a proctologic examination and pain was measured using a visual analog scale. THD Levorag(®) Emulgel was applied every 12 h for 40 days. Monitoring was scheduled at 10, 20 and 40 days. At time 0 and at the end of treatment, patients underwent anorectal manometry, if possible. RESULTS: Two hundred eighty-four AF patients were recruited (171 acute fissures). Complete healing was achieved in 47.9 % of the cases, an improvement in 31.0 % (global efficacy 78.9 %). In patients with acute fissure, the rate of efficacy was 89.4 % (complete healing: 64.3 %, improvement: 25.1 %), in those with chronic fissure the rate of efficacy was 62.8 % (complete healing: 23 %, improvement: 39.8 %), p < 0.001. Pain and resting anal pressure decreased significantly after treatment. CONCLUSIONS: Treatment with THD Levorag(®) Emulgel proved to be effective for the reepithelization of AF and the reduction of pain in the short term in about 80 % of patients.

Meta-analysis: long-term therapy with rifaximin in the management of uncomplicated diverticular disease.

BACKGROUND: Diverticular disease of the colon is a common gastrointestinal disease. Although most patients remain asymptomatic for their whole life, about 20-25% present symptoms related to 'diverticular disease'. Several randomised trials verified efficacy of a poorly absorbed antibiotic, such as rifaximin-α (rifaximin), in soothing symptoms and preventing diverticulitis. AIM: To evaluate the long-term efficacy administration of rifaximin plus fibre supplementation vs. fibre supplementation alone, on symptoms and complications, in patient with symptomatic uncomplicated diverticular disease. METHODS: Pertinent studies were selected from the Medline, and the Cochrane Library Databases, references from published articles and reviews. Conventional meta-analysis according to DerSimonian and Laird method was used for the pooling of the results. The outcomes were 1- year complete symptom relief, and 1- year complication incidence. The rate difference (RD, with 95% CI) and the Number Needed to Treat (NNT) were used as measure of the therapeutic effect on each outcome. RESULTS: Four prospective randomised trials including 1660 patients were selected. The pooled RD for symptom relief was 29.0% (rifaximin vs. control; 95% CI 24.5-33.6%; P<0.0001; NNT=3). The pooled RD for complication rate was -1.7% in favour of rifaximin (95% CI -3.2 to -0.1%; P=0.03; NNT=59). When considering only acute diverticulitis, the pooled RD in the treatment group was -2% (95% CI -3.4 to -0.6%; P=0.0057; NNT=50). CONCLUSIONS: In symptomatic uncomplicated diverticular disease, treatment with rifaximin plus fibre supplementation is effective in obtaining symptom relief and preventing complications at 1 year.

Infliximab in Crohn's disease: early and long-term treatment.

The natural history of Crohn's disease is characterized by a remitting and relapsing course that progresses to complications and surgery in the majority of patients. Current treatment guidelines advocate a stepwise approach according to disease location and severity at presentation, with goals mainly aimed at inducing and maintaining clinical remission. Major advances in the understanding of the pathogenesis of Crohn's disease offered significant opportunities for the development of new therapies over the past years. Infliximab and other biologic agents have shown impressive results in Crohn's disease patients refractory to standard therapy, suggesting a potential disease course-modifying action. These led to the proposal to reverse the traditional therapeutic algorithms using these agents early in the course of the disease. Preliminary data suggest that early intervention may be a more effective treatment strategy in some Crohn's disease patients. As yet, early and indiscriminate use of biologics remains to be supported by convincing evidence. Data on long-term treatment of Crohn's disease with infliximab or other biologics are even more scarce. Future studies aimed to identify predictors of complicated disease and long-term randomized studies aimed to compare "step-up" and "top-down" strategies in high-risk groups should help to answer if early introduction of biological therapy alters the natural history of Crohn's disease.

Tumor necrosis factor-alpha antagonism improves endothelial dysfunction in patients with Crohn's disease.

This study assessed the presence of endothelial dysfunction in patients with inflammatory bowel diseases (IBDs) and evaluated the possible role of tumor necrosis factor (TNF)-alpha in the pathophysiology of this abnormality. Similar elevations in circulating markers of inflammation (C-reactive protein and interleukin-6) were observed in Crohn's disease and ulcerative colitis compared to controls. Endothelium-dependent vasodilation to acetylcholine was impaired in Crohn's disease, but not in ulcerative colitis. Endothelium-independent vasodilation to sodium nitroprusside, by contrast, was not different among the three groups. The TNF-alpha neutralizing antibody, infliximab, enhanced the responsiveness to acetylcholine, but not to nitroprusside, in Crohn's disease, without modifying vascular responses to both drugs in ulcerative colitis. In conclusion, despite comparable degrees of systemic inflammation in the two IBDs, endothelial dysfunction is a selective feature of Crohn's disease and is beneficially affected by intravascular TNF-alpha neutralization. These findings underscore the role of selective cytokine targeting in improving endothelial function in patients with Crohn's disease.

Growth hormone in inflammatory bowel disease.

Crohn's disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract characterized by chronic relapsing inflammation and catabolism. Growth hormone/insulin-like growth factor-I axis is important in inflammatory bowel disease, because of the effects on epithelial cell kinetics, collagen deposition and immunomodulation. The potential of growth hormone as a therapeutic option in inflammatory bowel disease has been proven in various clinical settings. Acquired growth hormone resistance in inflammatory bowel disease seems to be mediated by a combination of undernutrition and active inflammation. In particular, proinflammatory cytokines, such as TNF-a and interleukin-6, have been implicated as potential mediators of growth hormone resistance. The introduction of anti-TNF-alpha monoclonal antibodies has proven very efficacious in patients with inflammatory bowel disease. By reducing cytokines levels in inflammatory cells of intestinal mucosa, infliximab could interfere with cytokine-induced growth hormone resistance. Recent in vivo data have shown that acquired growth hormone resistance in patients with inflammatory bowel disease may be reversed after the administration of anti-TNF-alpha therapy.

Sacroileitis and peripheral arthropathy associated with ulcerative colitis: effect of infliximab on both articular and intestinal symptoms.

Infliximab has been proven to be an effective therapy in a miscellany of rheumatic diseases and has been approved for the treatment of moderate-to-severe Crohn's disease with an inadequate response to conventional therapy and for the management of enterocutaneous fistulas. Data about the role of infliximab in ulcerative colitis are still controversial. Here, we report a case of a patient with sacroileitis and peripheral arthropathy associated with left-sided ulcerative colitis who achieved a sustained clinical remission after infliximab therapy.

Infliximab in the treatment of steroid-dependent ulcerative colitis.

BACKGROUND AND OBJECTIVES: Infliximab has proven efficacious in the treatment of Crohn's disease. Limited and contrasting data are available on effectiveness of anti-TNF alpha therapy in ulcerative colitis. We evaluated the efficacy of infliximab in the management of steroid-dependent ulcerative colitis. METHODS: We report preliminary data from a randomized, open-label, methylprednisolone-controlled trial of infliximab in the induction and maintenance of remission of patients with moderate to severe steroid-dependent ulcerative colitis. Twenty patients received either three infusion of infliximab (5 mg/kg) at 0, 2 and 6 weeks and thereafter every 8 weeks (group A) or methylprednisolone (0,7-1 mg/kg) daily for one week followed by a tapering regimen up to the minimal dose to maintain a symptom-free condition (group B). Clinical remission was defined as a DAI score less than 3. RESULTS: Ten patients in group A (DAI: 8.9+/-1.4) achieved remission after the first infusion (DAI: 1.6+/-0,7; p = 0.005) and steroids were progressively discontinued. At present (mean follow-up: 9.8+/-1.1 months), 9 out of 10 patients maintain clinical remission, while one patient relapsed at 3 months. Ten patients in group B (DAI: 8.7+/-1.4) reached clinical remission at one week (DAI: 1.9+/-0.3; p = 0.005). Eight out of 10 patients were maintained at a minimal steroid dosage without any relapse at 9.7+/-1.0 months follow-up. Two patients relapsed at 6 and 8 months, respectively. CONCLUSIONS: Infliximab seems to be as effective as steroids in the management of moderate to severe steroid-dependent ulcerative colitis. These preliminary data suggest the potential efficacy of repeated treatment with infliximab for short-term maintenance of remission and steroid withdrawal in glucocorticoid-dependent ulcerative colitis.