P406. Predictive factors of refractory to tacrolimus therapy in patients with active ulcerative colitis
Y. Yokoyama1, K. Watanabe2, N. Hida1, K. Nogami1, K. Kamikozuru1, K. Tozawa1, K. Nagase1, K. Fukunaga1, T. Matsumoto1, 1Hyogo College of Medicine, Department of Internal Medicine, Division of Lower Gastroenterology, Nishinomiya, Japan, 2Graduate School of Medicine, Osaka City University, Department of Gastroenterology, Osaka, Japan
Although tacrolimus (TA) is recognized as an effective therapy for induction remission in intractable patients with ulcerative colitis (UC), there are some refractory cases in spite of appropriate TA dose adjustment. Therefore, the evaluation of predictors for refractory including surgery is important issue for suitable treatment strategy. The aim of the present study is to investigate the predictors for refractory to TA therapy in patients with active UC.
Forty-seven patients who had been treated with TA for active intractable UC were investigated retrospectively. Clinical UC activity was assessed with the Lichtiger's clinical activity index (CAI) and Mayo score. The refractory case was defined as underwent surgery or changing to alternative treatment during TA therapy with high trough level (10–15 ng/ml, at least 7 days). We compared to evaluate the predictors between the response group and refractory group with multivariate analysis for patients' demographic variables.
The median of age was 35.5 years, duration of disease was 4.5 years, CAI was 10.3 and Mayo score was 8.0 for enrolled patients. Nine cases (19.1%) were refractory to TA therapy. Among them, 7 cases underwent surgery and 2 cases were changed to infliximab. The median interval from the achieving high TA trough level to the evaluation as TA-refractory was 18.7 days (7–34days). At baseline, both of CAI and Mayo score were significantly higher in the refractory group than the response group (p = 0.016 and p = 0.023, respectively). And the dose of prednisolone (PSL) at baseline was also significantly higher in the refractory group than the response group (p = 0.005). Multiple logistic regression analysis showed that high daily PSL dose (p = 0.032, 95% CI 1.014–1.363) at baseline and high CAI score at 7 days after achieving high trough level (p = 0.047, 95% CI 1.007–3.065) were significant predictive factors for the refractory to TA therapy.
Higher activity and higher daily PSL dose at baseline, poor response at 7 days after achieving high trough level were predictive factors for refractory to TA therapy. These refractory patients should be changed to alternative treatment including surgery without missing the appropriate timing.