Tolerability and usefulness of mercaptopurine in azathioprine-intolerant Japanese patients with ulcerative colitis

Background and Aim: Azathioprine (AZA) and mercaptopurine (6-MP) are established as effective therapeutic drugs for the induction and maintenance of remission in patients with ulcerative colitis (UC). However, AZA is often intolerable due to adverse effects. Evidence regarding the approach of switching from AZA to 6-MP in patients of Asian ethnicity is lacking. We assessed the tolerability and usefulness of 6-MP in Japanese UC patients who had shown intolerance to AZA. Methods: One-hundred and ten UC patients who had been treated with AZA and/or 6-MP from January 1985 to October 2008 were examined retrospectively. Results: Among 110 patients, 107 were treated first with AZA; only three were treated first with 6-MP. Thirty-five (33%) of the 107 patients were intolerant of AZA, with adverse effects including myelosuppression (8/35, 23%), hepatotoxicity (8/35, 23%), and abdominal symptoms (6/35, 17%). Among 35 AZA-intolerant patients, 23 were switched to 6-MP treatment. The cumulative probability of colectomy was significantly higher in patients not treated with 6-MP than in patients treated with 6-MP (log-rank test, P = 0.0002). Among the 26 patients (23 AZA-intolerant and three AZA-untreated) treated with 6-MP, 22 (85%) could tolerate the therapy. Adverse effects due to 6-MP were abdominal symptoms (2/4), myelosuppression (1/4), and rash (1/4). The median initial dose of 6-MP was 20 mg/day, and the median final dose was 30 mg/day. Conclusions: 6-MP was tolerated in 83% of AZA-intolerant patients, and it was effective for maintenance therapy of UC patients. 6-MP treatment should be considered in AZA-intolerant patients.