Conventional medical management of ulcerative colitis: Azathioprine

Abstract

Induction therapy with cortisone for ulcerative colitis was first described by Dearing and Brown of Mayo Clinic in 1950 [1 ], and the final results of a randomized clinical trial by Truelove and Witts of Oxford in 1955 [2]. By 1965, Lennard-Jones and colleagues had definitively shown that prednisone was not effective in maintaining remission in ulcerative colitis [3]. Alternative immunosuppressive agents were sought which would maintain a clinical remission and spare the side-effects of longterm corticosteroids. Azathioprine (AZA) was originally demonstrated as a therapy for ulcerative olitis in 1966 by Bowen and colleagues at the University of Chicago [4]. In an open-label case series, ten hospitalized patients were treated with relatively high doses of AZA (4–6 mg/kg/day) which was then continued as an outpatient. Most patients improved; however, the results were confounded by other medications and lacked a control group [4]. In the subsequent four decades, controlled trials of AZA have revealed mixed results in induction and maintenance for ulcerative colitis [5– 8]. The role of AZA in the treatment of ulcerative colitis has continued to be debated due to its evidence base of predominantly heterogenous small clinical trials and the advent of biologic therapy. The following chapter on AZA in the treatment of ulcerative colitis emphasizes practical implications of pharmacology and metabolism, efficacy estimates from clinical trials, safety, and practical dosing and toxicity monitoring methods for clinical practice.