Although debate continues regarding the role of aminosalicylates for the treatment of mild-moderate CD, there is good evidence that sulfasalazine is efficacious for the treatment of colonic CD. There is less substantial evidence for alternative mesalamine agents. Nevertheless, the aminosalicylates are advocated as a first line therapy for mild-moderately active CD. The use of sulfasalazine in divided doses of 3 to 6 g/d, supported by the National Cooperative Crohn's Disease Study (NCCDS), is compromised, in up to 25% of patients, by side effects attributable to the sulfapyridine carrier molecule, such as headache, nausea, GI upset, and, in males, a transient reduction in number and motility of sperm. Rare but more serious hypersensitivity reactions include hemolytic anemia, neutropenia, rash, and hepatitis. In contrast to UC, where alternative azo bond delivery systems such as olsalazine and balsalazide are effective alternatives, in Crohn's colitis these agents have not been shown to be effective. There is more evidence, however, that alternative mesalamine formulations are comparable to sulfasalazine or antibiotics in Crohn's colitis, but less efficacious than corticosteroids. Mesalamine in doses up to 4.8 g/d has a similar side effect profile as placebo in clinical trials. Also, despite general use, there is scant available data regarding the utility of rectal mesalamine suppositories (1 to 1.5 g/d) for Crohn's proctitis or mesalamine enemas (1 to 4 g/d) for left-sided colitis.
Metronidazole (0.75 to 2 g/d) and ciprofloxacin (1 g/d), alone or in combination, are also commonly used as an alternative or in addition to aminosalicylates for mild-moderate colonic CD, particularly for patients with accompanying perianal disease or for individuals who have failed to respond to aminosalicylates and are not "sick enough" to warrant corticosteroid therapy. Colonic disease responds better to antibiotics than small bowel disease, and metronidazole is effective in treating perianal CD. The Cooperative Crohn's Disease Study in Sweden (CCDSS) showed 800 mg daily of metronidazole to be successful in Crohn's colitis that had failed to respond to sulfasalazine. Approximately 55% or patients randomized to ciprofloxacin, 1 g/d, or mesalamine, 4 g/d, will respond with clinical remissions. The combination of sulfasalazine and corticosteroids in the European Cooperative Crohn's Disease Study and a combination of antibiotics with budesonide are more effective that either agents alone for patients with CD of the colon.
Corticosteroids are effective inductive therapies for patients with moderate-severe Crohn's colitis or for patients with mild-moderate disease that has not responded to amino-salicylates and/or antibiotics. Controlled release budesonide formulations are also efficacious for mild-moderate CD involving the right colon, but are not effective for more distal colonic disease. Doses of 40 to 60 mg daily of prednisone (or up to 1 mg/kg/d) are initiated until a clinical response has been established. Subsequent tapering is "individualized" according to the rate of response. Generally, the dosage is gradually reduced by 5 mg/week until the drug can be ceased or symptoms flare. In the NCCDS, 78% of patients responded to steroids given in this way. The response to budesonide is somewhat less and neither systemic nor nonsystemic steroids are efficacious at preventing relapse. Indeed, after a course of corticosteroids, approximately 75% of patients will either have a flare of disease activity or become steroid-dependent within a year. The use of corticosteroids is further limited by their significant acute and chronic side effect profiles, including short term side effects of emotional lability, insomnia, hypertension, glucose intolerance, and acne; and long term complications that include cataracts, accelerated osteoporosis, avascular necrosis, and growth impairment in children. Glucocorticoid side effects are significantly reduced with budesonide formulations, but there is still a risk for systemic side effects, particularly if the 9 mg dosage is used as maintenance therapy. There is substantial empiric use, but no clinical trial data regarding the efficacy of topical (rectal) steroid applications for Crohn's colitis.
Nutritional therapy with elemental or polymeric oral or enteral feeding has been shown to be beneficial to small bowel CD, but the benefits for Crohn's colitis have yet to be established. Their utility has, primarily, been limited to pediatric use where elemental or polymeric diets may be initiated as an alternative to steroids for children and adolescents. Total parenteral nutrition is only indicated for severely malnourished patients or those unable to tolerate enteral feeding.
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