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* = Presenting author

P333 Long-term efficacy and safety of thiopurines in patients with steroid-dependent ulcerative colitis: a retrospective investigation

Y. Yokoyama*, T. Sato, M. Kawai, Y. Kita, K. Kamikozuru, T. Miyazaki, M. Iimuro, N. Hida, S. Nakamura

Hyogo College of Medicine, Department of Inflammatory Bowel Disease, Division of Internal Medicine, Nishinomiya, Japan

Background

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are the 2o thiopurines frequently administered to patients with ulcerative colitis (UC) for sustaining clinical remission. Further, in Japan, AZA was officially recommended for patients with steroid-dependent UC in 2006. Therefore, there is inadequate outcome reports on the clinical efficacy and safety of AZA in Japanese UC patients. With this background in mind, this investigation was undertaken to understand the long-term efficacy and safety of thiopurines in patients with steroid-dependent UC.

Methods

In a retrospective setting, we reviewed the safety and prognostic outcomes in 106 steroid-dependent UC patients who had received AZA or 6-MP as maintenance therapy between May 2008 and August 2014 at our university hospital. Remission was induced with either topical or oral prednisolone (PSL) or a 5-aminosalicylic acid preparation. Items we factored for investigations included rate of steroid-free remission, long-term prognosis and safety. Clinical remission was defined as Lichtiger’s clinical activity index (CAI) ≤ 4, whereas clinical relapse was defined as hospitalisation because of severe UC, the need for oral or topical PSL, and treatment related adverse events (AE).

Results

Amongst the patients, the average age was 43.2 ± 18.7 years, and the average duration of UC was 7.1 ± 7.4 years. At the start of thiopurine therapy, the average daily oral dose of PSL was 13.5 ± 9.5mg. In total, 85 patients had received AZA, and 11 had received 6-MP. The rates of clinical remission, steroid-free remission, and mucosal healing were 59.4% (63 of 106 patients) 50.0% (53 of 106), and 81.0% (17 of 21 patients in whom mucosal healing was investigated). Amongst the patients with steroid-free remission, the maintenance rate was 77.6% (38 of 49 patients) at 12 months, 59.4% (19 of 32) at 24 months, and 68.8% (11 of 16) at 36 months. Amongst the 106 patients, 44.3% (47) had experienced thiopurine related AE. The most common AE were hepatotoxicity (36.2%), nausea (25.6%), and alopecia (17.0%). However, most patients with AZA-related AE who switched to 6-MP did not experience any new AE (70.2%). Most AE had occurred within 6 weeks after starting thiopurine dosing.

Conclusion

According to the outcomes we have compiled in this retrospective investigation, thiopurines appear to have significant long-term efficacy in patients with steroid-dependent UC. However, in line with the widely known toxicity associated with thiopurines, the long-term clinical potential of thiopurines is limited by their toxicity. Accordingly, patients on thiopurines should be diligently monitored for AE when receiving these medications beyond 6 weeks.