P582 Effectiveness and nephrotoxicity of long-term tacrolimus administration in patients with ulcerative colitis
K. Haga*1, T. Shibuya1, K. Okahara1, M. Kamei1, M. Takahashi1, O. Nomura1, D. Ishikawa1, N. Sakamoto1, T. Osada2, A. Nagahara1
1Juntendo University School of Medicine, Department of Gastroenterology, Tokyo, Japan, 2Juntendo University Urayasu Hospital, Department of Gastroenterology, Urayasu, Japan
Tacrolimus (TAC) is a calcineurin inhibitor used for the management of refractory ulcerative colitis (UC), and it is effective for inducing remission. A number of studies have assessed the short-term efficacy of TAC. However, there are few reports on the effectiveness of long-term administration. TAC is also known to cause adverse effects including acute renal toxicity, but there are few studies focussed on renal function in UC. The aim of this study was to evaluate the long-term effectiveness, and monitor changes in renal function during prolonged TAC use in patients with UC.
Data were compiled from 49 moderate to severe active UC patients treated with TAC in Juntendo University. We adjusted the trough level with a range of 10–15 ng/ml for the initial 2 weeks and subsequently a range of 5–10 ng/ml. Their medical records were retrospectively reviewed. Clinical outcomes were assessed at 6 months, 1 year and 2 years after initiating TAC. We also monitored the chronological changes in renal function by following the estimated glomerular filtration rate (eGFR) and serum creatinine level during TAC administration. Plasma trough TAC level and dose were compared with renal function.
Thirty-six patients were treated with TAC for over 3 months. Relapse-free survival at 6, 12 and 24 months were 83%, 77% and 47%, respectively, and there were no patients who needed surgery. On the other hand, renal function was reduced in 38.9% patients showing a 30% decrease in the eGFR relative to baseline. We found that even after a long-term administration of TAC, eGFR tended to improve in most cases upon discontinuation, but in some patients, there was a significant decrease. Moreover, irreversible renal dysfunction was more likely to occur in cases where eGFR was reduced more than 30%.
Long-term administration of TAC appeared to prevent the relapse of UC. This study seem to demonstrate the potential use of TAC as an effective option in the long-term medical management of patients with UC. On the other hand, it tended to increase the risk of nephrotoxicity. In most cases, renal function may improve upon discontinuation or reducing the dose, but in some patients, long-term TAC may cause irreversible renal damage. There is a need for careful monitoring of renal function during TAC dosing.