TREATMENT Medical Induction of Active Crohn’s Ileitis: Evidence-based Management Kerri Novak, MD, Lloyd Sutherland, MD, and Remo Panaccione, MD A pproximately 70% of patients with Crohn’s disease (CD) will have terminal ileal involvement. This may represent isolated terminal ileitis (30%) or ileocolitis (40%). When treating patients with ileitis it is important to ascertain the true extent and severity of the disease. This review outlines the current evidence for medication efficacy in the induction of remission in isolated Crohn’s ileitis. Options for the Medical Induction of Remission in CD Sulfasalazine and Mesalamine Sulfalsalazine is metabolized to sulfapyridine and 5-aminosalicyclic acid (5-ASA), the active antiinflammatory agent, and was originally used as a modestly effective agent in the treatment of rheumatoid arthritis. Newer mesalamine formulations have been developed to enhance delivery and limit the toxicity associated with the sulfapyridine moiety. The immunosuppressive effects of 5-ASA are many and include inhibition of prostaglandin and leukotriene function, reduction of cytokine and free radicals production, as well as reduction of lymphocyte function and adhesion. Historically, these agents have been used to induce remission in mild to moderate CD. Trial data have shown efficacy of sulfasalazine in colonic disease; however, cumu- lative evidence shows it is less effective in active ileitis, in patients previously treated with corticosteroids, and it has greater response rates if combined with prednisolone. 1–3 Al- ternatively, mesalamine has equivocal if any efficacy in in- ducing remission of Crohn’s ileitis. 3,4 Although treatment of ileal CD with newer mesalamine agents is common, it is not supported by the evidence. Systemic Corticosteroids Use of the corticosteroids prednisone and prednisolone for the primary treatment of inflammatory bowel disease (IBD) has occurred since the early 1950s. The efficacy of corticosteroids in inducing remission in CD is well substan- tiated in the literature. 1,5,6 However, there is a concern of both short- and long-term systemic toxicity including metabolic bone disease, glucose intolerance, hypertension, cosmetic, and neuropsychiatric side effects. For this reason, the ideal agent would have similar efficacy as prednisone with less systemic side effects. Budesonide is a topical glucocorticoid with high intes- tinal mucosal affinity for the steroid receptor but is slightly less effective than conventional steroids in the induction of remission in CD. 7,8 After 10 weeks of oral controlled release busedonide (9 mg/day for 8 weeks and 6 mg/day for 2 weeks), 53% of patients were in remission compared to 66% of those receiving prednisolone (40 mg daily). However, this is offset by significantly fewer systemic side effects, such as osteoporosis, given its extensive first-pass hepatic metabo- lism and low potency of its primary metabolites. 8 The enteric coated formula has a pharmacokinetic profile that contributes to its efficacy as a topical agent and it has consistently shown to be more effective than 5-ASA or placebo in the induction of remission in CD. 9 Although effective in the induction of remission, systemic corticosteroids have not shown efficacy in maintaining remission. Budesonide is likely different: re- cently published pooled analysis of 4 double-blind, random- ized, placebo-controlled trials showed budesonide (6 mg/day) is effective in prolonging time to relapse at 3 and 6 months but not 12 months (10) Immunosuppressive Agents (Purine Antimetabolites and Methotrexate) The purine antimetabolites (6-mercaptupurine and aza- thioprine) are interchangeable immunomodulators that are effective steroid-sparing agents, useful in both induction and maintenance of disease remission. Both azathioprine (AZA) and mercaptopurine (MP) are purine analogs. The former is a prodrug metabolized to MP, which is then converted to thioguanine (TG). TG is incorporated into nuclear ribonucle- otides, inhibiting DNA production in replicating lympho- cytes, thereby impeding proliferation. It may also adversely affect natural killer and cytotoxic T-cell function, a direct antiinflammatory effect. AZA has been well studied in the context of CD: a meta-analysis including 8 randomized controlled trials (RCTs) by Sandborn et al 11 showed that both drugs are more effective compared to placebo in inducing remission in active disease. The number needed to treat (NNT) to induce remis- sion in 1 patient was 5, with a pooled odds ratio (OR) of 2.36 From the Division of Gastroenterology, Department of Medicine, Univer- sity of Calgary, Alberta, Canada. Copyright © 2008 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20711 Published online in Wiley InterScience (www.interscience.wiley.com). Inflamm Bowel Dis ● Volume 14, Number S2, A Clinician’s Guide to IBD S247