Conventional treatment of Crohn's disease: objectives and outcomes

Abstract

Despite conventional medical and/or surgical intervention, endoscopic and symptomatic relapse is common among individuals with Crohn's disease (CD). Treatment goals have therefore been refocused to include achieving control of active disease and maintaining remission with agents associated with a minimum of toxic adverse effects. Conventional treatment regimens have been used with varying success in regard to these therapeutic goals. Traditionally, aminosalicylates have been considered effective in inducing a response in some patients with mild-to-moderate CD but have demonstrated little or no long-term benefit in controlled clinical trials. Glucocorticosteroid therapy is associated with higher rates of response in patients with active CD; however, clinical benefits are frequently offset by the common occurrence of corticosteroid-related toxicity. Oral controlled-release budesonide has demonstrated comparable efficacy to prednisolone with less risk for adverse effects, although many questions remain regarding the long-term use of this agent. Response to standard immunosuppressive agents such as azathioprine and 6-mercaptopurine in patients with active disease may require 3 to 6 months from initiation of treatment. These agents are therefore considered most valuable as maintenance therapy, providing consistent long-term benefit in patients with chronic refractory or corticosteroid-dependent disease. Although the incidence of allergic adverse effects is relatively low with azathioprine/6-mercaptopurine, more serious adverse effects, including bone marrow suppression, hepatotoxicity, pancreatitis, and infectious complications, can occur. Limited success in the treatment of perianal disease has been achieved with antibiotics such as metronidazole and the immunosuppressives cyclosporine and azathioprine/6-mercaptopurine. Although broader use of immunosuppressive agents has allowed improvement in the maintenance of remission in patients with CD, long-term safety data with these agents are lacking, concerns about toxicity and the potential risk for neoplasia remain, and attenuation of response with chronic immunosuppressive use can occur. Therefore, innovative therapeutic approaches are needed to meet key treatment goals often not addressed by conventional therapies.