In Japan, tacrolimus is used to treat patients diagnosed with refractory ulcerative colitis (UC); however, there are few studies on the efficacy of tacrolimus treatment. The aim of this study was to analyze the short- and long-term outcomes of tacrolimus treatment in patients with refractory UC and to identify the prognostic factors associated with treatment outcomes.Methods:
Data were retrospectively collected from 52 patients diagnosed with refractory UC who were treated with tacrolimus at our hospital from 2009 to 2014. Patients had to have a Lichtiger clinical activity index (CAI) of ≥5 points at baseline. Response was defined as a CAI reduction of ≥4, and remission was defined as a CAI of ≤4. CAI was calculated at baseline and 2 and 12 weeks following tacrolimus administration. The cumulative non-colectomy rate and the sustained remission rate among patients who achieved remission after 12 weeks were estimated using the Kaplan–Meier method. Univariate analysis was used to identify the prognostic factors of remission at 2 and 12 weeks, the cumulative non-colectomy rate, and the sustained remission rates.Results:
Of the 52 patients (mean age, 38.5 yr), 17 were female. The mean duration of disease was 5.1 years. At baseline, the mean CAI and C-reactive protein (CRP) levels were 9.9 and 1.46 mg/dL. Thirty-four patients had pancolitis and 18 had left-sided colitis. In terms of steroid response, 28, 22, and 2 patients were classified as steroid-resistant, steroid-dependent, and steroid-intolerant, respectively. Concomitant treatment with 5-aminosalicylic acid, azathioprine or 6-mercaptopurine, and prednisolone was administered to 43, 28, and 24 patients, respectively. Twenty-five patients had previously undergone cytapheresis, and 30 patients had previously received infliximab. Two weeks after tacrolimus treatment, CAI and CRP levels significantly decreased from 9.9 to 6.1 and from 1.46 to 0.43 mg/dL, respectively. After 2 weeks, the response and remission rates were 54% and 37%, respectively, and after 12 weeks they were 40% and 37%, respectively. Younger age was significantly associated with a higher remission rate at 2 weeks, whereas previous infliximab treatment was significantly associated with lower remission rate at 12 weeks. The 1-, 3-, and 5-years cumulative non-colectomy rates were 59%, 57%, and 53%, respectively, and the 1-, 3-, and 5-years sustained remission rates were 73%, 43%, and 35%, respectively. Concomitant treatment with azathioprine or 6-mercaptopurine was significantly associated with higher rates of sustained remission. Previous treatment with infliximab and pancolitis significantly increased the risk of colectomy.Conclusions:
Approximately 40% of the Japanese UC patients treated with tacrolimus achieved remission after 12 weeks. However, 60% of these patients experienced a flare-up, and 50% of all patients required a colectomy within 5 years. Previous treatment with infliximab and pancolitis UC were significantly associated with poor outcomes following tacrolimus treatment, whereas concomitant treatment with azathioprine or 6-mercaptopurine was associated with favorable outcomes.