Safety and efficacy of azathioprine in the maintenance of ciclosporin-induced remission of ulcerative colitis

Background: It has been shown that azathioprine prolongs the response to ciclosporin of steroid-refractory ulcerative colitis, but no specific data are available concerning its toxicity in this indication. Aim and methods: The charts of 21 patients with steroid-refractory ulcerative colitis who received azathioprine overlapping with a successful ciclosporin course were reviewed for the onset of toxicity. The controls consisted of 48 initial responders to steroids who received azathioprine for steroid-dependence or resistance/toxicity. Results: Two of the 21 patients were withdrawn because of hypersensitivity to azathioprine. The remaining 19 were treated for a median of 18 months together with a median daily steroid dose of 35 mg: (10-75 mg) to be tapered off. Toxicity (31%) included leukopenia alone (two cases), cholestasis alone (one case), cholestasis and increased amylase (one case), increased amylase alone (one case), and cutaneous infection (one case). The frequency of withdrawal was 21%. The mean daily steroid doses were reduced from 38 mg to 3.8 mg in the study cohort, and from 25 mg: to 8 mg in the controls, among whom toxicity (27%) included four cases each of leukopenia and increased amylase, two cases each of alteration of liver enzymes and infection, and one case of gastric intolerance. Ten of the 48 controls (20%) were withdrawn from the study. Conclusion: Azathioprine is as effective and safe in the maintenance of the response of patients with steroid-refractory ulcerative colitis to ciclosporin as it is in the treatment of those who respond to steroids.