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Abstract: 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. Methods: A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7–9), uncertain (4–6 and/or disagreement) and inappropriate (1–3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost. Results: Three hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNFα antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a “wait-and-see” strategy. Factors that influenced the panel''s voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNFα agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial. Conclusion: Detailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNFα agents are now freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. [Copyright &y& Elsevier]

Abstract: 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. In anti-TNF naïve patients, budesonide and prednisone were found to be appropriate for mild-moderate CD, and infliximab (IFX) was appropriate when these had previously failed or had not been tolerated. In patients with a prior successful treatment by IFX, this drug, with or without co-administration of a thiopurine analog, was favoured. Other anti-TNFs were appropriate in the presence of intolerance or resistance to IFX. High-dose steroids, IFX or adalimumab were appropriate in severe active CD. For the 105 indications for ST-D or ST-R disease, the panel considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for limited resection, to be appropriate, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. Conclusion: Steroids, including budesonide for mild-to-moderate CD, remain the first-line therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the amount of available evidence, remain the second-line therapy for most indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D patients and ST-R patients. [Copyright &y& Elsevier]

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%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. Purine analogues, methotrexate and infliximab have all shown efficacy in achieving steroid-free remission in patients with steroid-refractory or steroid-dependent disease. Other fast-acting immunosuppressors showed little benefit. Surgery may be indicated in this setting. Natalizumab may prove useful in patients refractory to infliximab and other anti-TNF agents. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. There is a trend towards a prolonged time to relapse in patients in remission who are treated with budenoside, a corticosteroid with high topical anti-inflammatory activity and low systemic activity. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn’s disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Only a few studies in small numbers of patients have been published on the use of tacrolimus. There is a lack of convincing evidence of efficacy of mycophenolate mofetil. The use of anti-TNF agents may change the future approach to maintenance therapy for Crohn’s disease. Patients who responded clinically to infliximab, adalimumab and certolizumab have maintained their clinical response when receiving repeat infusions or subcutaneous injections, respectively. In patients refractory to other therapies, infliximab may be effective in maintaining remission. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Patients with moderate to severe disease and patients with steroid-refractory or steroid-dependent disease differ in their management, as the latter groups usually include patients with less acute situations. Systemic corticosteroids represent the mainstay of the management of moderate to severe disease and remain the first-line therapy in this setting. Infliximab is the choice alternative for patients who do not respond to steroids or in whom steroids are contraindicated. Purine analogues, methotrexate and infliximab have shown efficacy in achieving steroid-free remission in patients with steroid-refractory or -dependent disease. Other fast-acting immunosuppressors showed little benefit. Surgery may be indicated in this setting. Nataluzimab may prove useful in patients refractory to infliximab. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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 lesions. 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 correlates with disease activity, adequate therapy is a central goal of the overall patient management. Treatment options include mainly sulfasalazine, budesonide and systemic steroids, while the role of mesalazine and antibiotics remains controversial. The role of biological therapies in mild to moderate disease has not been thoroughly evaluated and will not be discussed here. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

When remission of Crohn’s disease is achieved, the next goal is to maintain long-term remission. Aminosalicylates may be recommended for maintenance remission, even though the results are less consistent than those observed in ulcerative colitis. The benefit is mainly observed in the post-surgical setting and in patients with ileitis, and with a prolonged disease duration. Corticosteroids are not effective in maintaining remission and should not be used for this indication. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn’s disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Mycophenolate mofetil could be considered a therapy in patients who are either allergic to azathioprine or in whom azathioprine failed to induce remission. The use of infliximab may change the future approach to maintenance therapy for Crohn’s disease. Patients who responded clinically to infliximab have maintained their clinical response when receiving repeat infusions at 8-week intervals. In patients refractory to other therapies, infliximab may be effective in maintaining remission. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]