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* = Presenting author

P596 Efficacy and Nephrotoxicity of Long-term Maintenance Therapy with Tacrolimus in Patients with Ulcerative Colitis

S. Tsuda*1, R. Kunisaki1, T. Ogashiwa1, H. Yasuhara1, R. Koh1, S. Tsunoda1, S. Yamamoto1, N. Kawashima1, R. Kubota1, K. Yazawa1, K. Goto1, H. Kimura1, S. Maeda2

1Yokohama City University Medical centre, Inflammatory Bowel Disease Centre, Yokohama, Japan, 2Yokohama City University Graduate School of Medicine, Gastroenterology, Yokohama, Japan

Background

Biological therapy has at least in the short term reduced the number of patients requiring colectomy for fulminant ulcerative colitis (UC). However, alternative medications are to be available for patients who are intolerant or lose response to biologics. Tacrolimus (Tac) has shown efficacy as remission induction therapy in UC patients, but the long term outcomes and safety of UC patients treated with Tac as maintenance therapy remain to be described. This study was to evaluate efficacy and nephrotoxicity of long-term maintenance therapy with Tac in patients with UC.

Methods

In a single tertiary centre setting, 139 patients with UC treated with oral Tac between 2009 and 2014 were included for evaluation. Blood Tac levels were maintained at 10-15 ng/mL for the initial 2 weeks, and at 5-10 ng/mL beyond 2 weeks. Among the 139 patients, 89 had received Tac for 3 to 4 months. At this time point, responders to Tac could discontinue with Tac, and patients who could not discontinue corticosteroids, patients who did not achieve remission, or mucosal healing, could continue receiving Tac as maintenance therapy. Nephrotoxicity was monitored by measuring serum creatinine and glomerular filtration rate (GFR), defined as >150% rise in serum creatinine or a reduction of >15% in GFR.

Results

Sixty-three patients received oral Tac maintenance therapy, 53 (90%) of these were taking aminosalicylates and 41 (69%) were taking thiopurines as concomitant medications. During a median follow up time of 29 months, range 4.1 - 69 months, 38 patients (60%) relapsed; 20 (48%) received biologics, and 15 (25%) underwent colectomy. The Kaplan-Meier survival analysis showed an overall relapse-free rate of 48% at 1 year, and 31% at 3 or 5 years. Non-switching to biologics was 74% at 1 year, 52% at 3 years, and 26% at 5 years. The colectomy-free rate was 91% at 1 year, 77% at 3 years, and 73% at 5 years. For patients who received oral Tac over 1 year, relapse-free rate was 64% at 1 year, 46% at 3 or 5 years. The rate of non-switching to biologics was an 80% at 1 year, 67% at 3 years, and 21% at 5 years. The colectomy-free rate was 100% at 1 year, and 81% at 3 years. Nephrotoxicity was found in 58% patients. Mostly reversible and no patient needed haemodialysis, but renal function did not fully recover in 13% of the patients 1 year after discontinuation of Tac.

Conclusion

Long-term maintenance therapy with Tac was significant in patients with refractory UC. However, nephrotoxicity by Tac is a serious issue in clinical settings and needs to be closely monitored during Tac therapy including a regular observations on Tac trough levels.