P-086 Short-Term and Long-Term Therapeutic Outcomes of Tacrolimus Treatment for Refractory Ulcerative Colitis, and the Prognostic Factors for Surgery

Abstract

Little is known about the long-term therapeutic outcomes of tacrolimus (Tac) treatment for refractory ulcerative colitis (UC) and the prognostic factors for surgery. The aim of this study was to ascertain both the short- and long-term therapeutic outcomes of Tac for refractory UC and the prognostic factors for surgery. A total of 66 refractory UC patients (median age, 39 years; median disease duration, 43 months; median disease activity index [DAI] score, 11) undergoing treatment with Tac at our hospital between 2004 and 2012 were enrolled in this study. This study investigated the following items:(1) short-term clinical response was evaluated based on a partial DAI score (DAI score without endoscopy) at week 6. Remission was defined as a partial DAI score of 1 point or lower. Improvement was defined as a reduction in partial DAI score of more than 3 points, but not a remission. No response was defined other than above; (2) long-term therapeutic outcomes, with the overall cumulative colectomy -free survival was calculated using the Kaplan-Meier method. We also calculated a Colectomy-free survival according to short-term efficacy of tacrolimus; (3) factors affecting short-term surgery, assessed by comparing clinical attributes, laboratory findings, and endoscopic findings at the time of first Tac use both in patients who underwent short-term surgery and in those who did not. Multivariate analysis was also performed. (1) Six weeks after starting Tac, 19 patients had achieved remission, 29 had achieved improvement, and no response was seen in 18, indicating a short-term efficacy rate of 48/66 (73%). Ten of the 18 patients in whom no response was seen underwent surgery within 6 weeks of starting Tac, indicating a short-term surgery avoidance rate of 56/66 (85%). (2) The median follow-up period was 32.8 months, and 18 of the 66 patients (27%) underwent surgery, with a cumulative colectomy-free survival was estimated to be 67% at 98 months. The colectomy-free survival was significantly higher in the group with a favorable short-term response to tacrolimus than the group with an unfavorable response (P = 0.026). (3) Multivariate analysis revealed that deep excavated ulcers were a risk factor for short-term surgery (odds ratio, 13.4; 95% confidence interval [CI], 1.5–117.2). Tac was effective for inducing clinical remission of patients with steroid refractory ulcerative colitis, although approximately one-third of patients required surgery in the long term. Deep excavated ulcers were a risk factor for short-term surgery, and poor short-term response to Tac was a risk factor for long-term surgery. Our study suggested that it might be important to take these risk factors into consideration when evaluating the use of Tac.