P448 Remission induction therapy with tacrolimus and biological combination therapy for severe ulcerative colitis

Abstract

Remission induction therapy with tacrolimus (TAC) and biological agents (bio) has been shown to be effective for ulcerative colitis (UC). Monotherapy with bio or TAC may fail to achieve remission, and surgical treatment is required in some patients. We perform combined TAC and bio therapy for remission induction after hospitalising patients if remission cannot be achieved with TAC or bio monotherapy alone, although such cases are rare. We performed this study to clarify the efficacy and problems of concomitant treatment with TAC and a biological agent. The subjects were 11 patients with UC who underwent combined TAC and bio therapy for the induction of remission at our hospital from April 2000 to August 2017. We classified the patients into a remission group and a non-remission group, and we assessed the recurrence rate in the remission group. Remission was defined as a Lichtiger clinical activity index (CAI) <4 at ≥4 weeks after achieving remission. Recurrence was defined as the need to re-induce remission in the patient by intensive intravenous steroid therapy, switching to a bio, the re-administration of TAC, or the up-titration of the TAC dose to increase the trough blood level (≥10 ng/dl). In the remission group, azathioprine was administered concomitantly to all patients who did not develop side effects. We compared the two groups with respect to the following factors: (1) remission induction rate, (2) sex, age at onset (years), disease extent, disease duration (years), pre-treatment symptoms (CAI), Alb, Hb, CRP, colonoscopic scores (Mayo and UCEIS), total prednisolone dose during hospitalisation (mg), prior treatment (TAC or bio), time to achieve the target TAC trough blood level (days), (3) adverse events, and (4) the recurrence rate. The remission induction rate was 54%. Significant differences (p < 0.05) were observed between the remission and non-remission groups in the disease duration (9.6 ± 3.9 vs. 3.3 ± 4.0 years) and pre-treatment serum Alb level (3.8 ± 0.3 vs. 2.9 ± 0.4), respectively. Adverse events included renal impairment (n = 2), tremor (n = 2), influenza (n = 1), and cytomegalovirus positivity (n = 3). After achieving remission, the recurrence rate was 37% at 100 days, 66% at 200 days, and 83% at 400 days. We observed some efficacy of combined TAC and bio for UC. This combination therapy was more effective in the patients with a longer disease duration and a high serum Alb level before treatment. No serious complications were observed. However, the recurrence rate was high, and further investigations of adverse events are necessary. Although many issues remain to be addressed, combined TAC and bio therapy could be an option for remission induction in UC as various biological agents become available.