Management of fistulas in patients with Crohn’s disease: Antibiotic to antibody

8 Apr
2012

Antibiotic to antibodyFistulization is a common complication of Crohn’s dis- internal or external. While fistulas between adjacent bowel ease. The clinical significance of a fistula results from its loops are frequent and often not symptomatic, internal fis-localization and symptomatic consequences. Fistulas can be tulas between distant sites (gastrocolic, rectovaginal, rectovesical) may cause severe complications. External fistulas are communications between the intestine and the skin; the most common sites of occurrence are the perineum and the abdominal wall. Because fistulas are usually associated with active inflammatory disease, they tend to be chronic. When fistulas are present for several weeks, spontaneous closure occurs uncommonly. In a placebo controlled trial, the rate of closure of chronic fistulas in patients not treated with an immunosuppressive drug was 6% over two years. Surgery itself has not changed the morbidity of fistulas much; improved parasurgical modalities, including parenteral nutrition, have been more beneficial in the general management of these patients.

The majority of lesions observed in therapeutic clinical trials of patients with fistulizing Crohn’s disease have been perianal and other enterocutaneous fistulas. Perianal fistulas are more often associated with colonic disease than with small bowel disease. One-third of patients with colonic Crohn’s disease have perianal fistulas; these patients are more likely to follow a chronic continuous disease course than patients without fistulas. The probability that a patient will require surgical resection (permanent ileostomy) due to fistula disease is increased in those with perianal fistulas (52% compared with 23% in those without perianal fistulas, at 20 years; relative risk 2.1).
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Various therapies for the management of Crohn’s disease have been reported to be effective in both uncontrolled and controlled trials. However, the effects of commonly used drugs such as 5-aminosalicylic acid, steroids and budesonide on fistulization have not specifically been reported. Also, recent clinical trials of novel therapies, such as Rh interleukin-10, Rh interleukin-11, intercellular adhesion molecule-1, antisense oligonucleotide and anti-integrin alpha-4, beta-7 monoclonal antibody, have not reported the outcomes of fistulas.

Most trials designed specifically to assess the closure of fistulas have been uncontrolled (antibiotics, cyclosporine, methotrexate and thalidomide); only two drugs — azathio-prine (AZA) or 6-mercaptopurine (6-MP), and infliximab — have been evaluated in randomized, placebo controlled studies. Most of the trials have enrolled a small number of patients — usually patients who were refractory to other therapies and with enterocutaneous fistulas (perianal fistulas in the majority). End points have usually been defined (closure or improvement), although outcome criteria have not always been provided or have been variable among studies (improvement scale, time to response at onset or at a scheduled visit). Also, results have been reported differently, according to the number of fistulas or the number of patients with fistulas. Future studies should be standardized, for example by incorporating the perianal disease activity index and the Present-Korelitz system.

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