Appropriateness and long-term discontinuation rate of biological therapies in ulcerative colitis.

Background: Anti-TNFα agents are commonly used for ulcerative colitis (UC) therapy in the event of non-response to conventional strategies or as colon-salvaging therapy. The objectives were to assess the appropriateness of biological therapies for UC patients and to study treatment discontinuation over time, according to appropriateness of treatment, as a measure of outcome.

Methods: We selected adult ulcerative colitis patients from the Swiss IBD cohort who had been treated with anti-TNFα agents.

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel.

Background: Safety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question.

Methods: Multidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission.

Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): Results of a multidisciplinary international expert panel-EPACT II.

Introduction: High-grade evidence is lacking for most therapeutic decisions in Crohn's disease. Appropriateness criteria were developed for upper gastro-intestinal, extra-intestinal manifestations and drug safety during conception, pregnancy and breastfeeding in patients with Crohn's disease, to assist the physician in clinical decision making.

Methods: The European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT II), a multidisciplinary international European expert panel, rated clinical scenarios based on evidence from the published literature and panelists' own clinical expertise.

Appropriate therapy for fistulizing and fibrostenotic Crohn's disease: Results of a multidisciplinary expert panel - EPACT II.

Introduction: Many therapeutic decisions in the management of fistulizing and fibrostenotic Crohn's disease (CD) have to be taken without the benefit of strong scientific evidence. For this reason, explicit appropriateness criteria for CD fistula and stenosis treatment were developed by a multidisciplinary European expert panel in 2004 with the aim of making them easily available on the Internet and thus allowing individual case scenario evaluation; these criteria were updated in 2007.

Methods: Twelve international experts convened in Geneva, Switzerland in December 2007.

Appropriate maintenance treatment for Crohn's disease: Results of a multidisciplinary international expert panel - EPACT II.

Introduction: Biological therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNFα inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating.

Appropriateness of therapy for active Crohn's disease: Results of a multidisciplinary international expert panel-EPACT II.

Unlabelled: The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not filled all the gaps in our knowledge and thus, in clinical practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence.

Methods: A multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD.

Results: Overall, 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated.

Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness.

Objective: Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients.

Methods: EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

Objective: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD).

Material And Methods: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients).

Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study.

Background/aims: Treatment of chronic HCV infection has become a priority in HIV+ patients, given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluate and compare antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HIV-HCV co-infected and HCV mono-infected patients, and to examine whether 6 months of therapy would have the same efficacy in HIV patients with favourable genotypes 2 and 3 as in mono-infected patients, to minimise HCV-therapy-related toxicities. Secondary endpoints were to evaluate predictors of sustained virological response (SVR) and frequency of side-effects.

The effect of nonmedical factors on variations in the performance of colonoscopy among different health care settings.

Background: Previous published studies have shown significant variations in colonoscopy performance, even when medical factors are taken into account. This study aimed to examine the role of nonmedical factors (ie, embodied in health care system design) as possible contributors to variations in colonoscopy performance.

Methods: Patient data from a multicenter observational study conducted between 2000 and 2002 in 21 centers in 11 western countries were used.

Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication.

HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients.

Drug safety in Crohn's disease therapy.

The management of Crohn's disease usually consists of a succession of short-term acute phase treatments followed by a long-term maintenance therapy. Above all the most frequent adverse events and the data on the long-term safety of the therapeutic arsenal available to the physician will be taken into consideration. The drugs described in this article include 5-ASA compounds, antibiotics (metronidazole, ciprofloxacin and rifaximin), corticosteroids (budesonide, prednisone and equivalents), thiopurines (azathioprine and 6-mercaptopurine), methotrexate, anti-tumor necrosis factor inhibitors (infliximab, adalimumab, certolizumab), natalizumab, anticalcineurin inhibitors (cyclosporine, tacrolimus) and mycophenolate mofetil.

Pregnancy and breastfeeding in patients with Crohn's disease.

Crohn's disease commonly affects women of childbearing age. Available data on Crohn's disease and pregnancy show that women with Crohn's disease can expect to conceive successfully, carry to term and deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health.

Extraintestinal manifestations of Crohn's disease.

In each case of extraintestinal manifestations of Crohn's disease, active disease, if present, should be treated to induce remission, which may positively influence the course of most concomitant extraintestinal manifestations. For some extraintestinal manifestations, however, a specific treatment should be introduced. This latter part of disease management will be discussed in this chapter, in particular for pyoderma gangrenosum, uveitis, spondylarthropathy - axial arthropathy - and primary sclerosing cholangitis, which have also been described in quiescent Crohn's disease.

Upper gastrointestinal Crohn's disease.

Symptomatic gastroduodenal manifestations of Crohn's disease are rare, with less than 4% of patients being clinically symptomatic. Gastroduodenal involvement may, however, be found endoscopically in 20% and in up to 40% of cases histologically, most frequently as Helicobacter pylori-negative focal gastritis, usually in patients with concomitant distal ileal disease. In practice, the activity of concomitant distal Crohn's disease usually determines the indication for therapy, except in the presence of obstructive gastroduodenal symptoms.

Maintenance of surgically induced remission of Crohn's disease.

At 1 year after a first resection, up to 80% of patients show an endoscopic recurrence, 10-20% have clinical relapse, and 5% have surgical recurrence. Smoking is one of the most important risk factors for postoperative recurrence. Preoperative disease activity and the severity of endoscopic lesions in the neoterminal ileum within the first postoperative year are predictors of symptomatic recurrence.

Maintenance of medically induced remission of Crohn's disease.

The natural history of Crohn's disease is characterized by recurring flares alternating with periods of inactive disease and remission. This implies that most patients need to take medication for a large period of their life, mostly for maintenance of remission and, intermittently, additional therapy during a flare. Low-dose systemic corticosteroids are not effective in maintaining remission and should not be used for this indication.

Fibrostenotic Crohn's disease.

Crohn's disease is often complicated by gastrointestinal strictures. Postoperative recurrence at the anastomotic site is common and repeated surgical interventions may be necessary. Medical treatment may relieve active inflammation (see chapter on active luminal disease) but fibrous strictures will not respond to this.

Fistulizing Crohn's disease.

Fistulas are common in Crohn's disease. A population-based study has shown a cumulative risk of 33% after 10 years and 50% after 20 years. Perianal fistulas were the most common (54%).

Severe and steroid-resistant Crohn's disease.

Patients with moderate-to-severe disease and patients with steroid-refractory or steroid-dependent disease differ in their management, as the latter two groups usually involve patients whose condition is less acute. Systemic corticosteroids represent the mainstay of the management of moderate-to-severe disease and remain the first-line therapy in this setting. Anti-TNF agents represent choice alternatives for patients who do not respond to steroids or in whom steroids are contraindicated.

Mild-to-moderate active luminal Crohn's disease.

The management of luminal Crohn's disease, the most common form of initial presentation of the disease, depends on the location and the severity of the disease. Mild-to-moderate disease represents a relatively large proportion of patients with a first flare of luminal disease, which may also be associated with perianal disease. As quality of life of these patients inversely correlates with disease activity, adequate therapy is a central goal of the overall patient management.

EPACT II: project and methods.

Building on the first European Panel on the Appropriateness of Crohn's Disease Treatment (EPACT I) which was held in Lausanne at the beginning of March 2004, a new panel will be convened in Switzerland (EPACT II, November to December 2007) to update this work. A combined evidence- and panel-based method (RAND) will be applied to assess the appropriateness of therapy for Crohn's disease (CD). In preparation for the meeting of experts, reviews of evidence-based literature were prepared for major clinical presentations of CD.

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C.

Background/aim: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis.

Interferon and ribavirin with or without amantadine for interferon non-responders with chronic hepatitis C. A randomized, controlled pilot study.

Background/aims: Treatment options for interferon-non-responders (INF-NR) with chronic hepatitis C are limited. Our aim was to compare efficacy and tolerability of an interferon-alfa-2a (INF), ribavirin (RIBA) and amantadine (AMA) combination with those of an INF and RIBA combination.

Methods: 30 patients with biopsy proven chronic hepatitis C were randomised to INFRIBA-AMA or INF-RIBA, stratified according to genotype (1/4 versus 2/3) and presence or absence of cirrhosis.