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P465. Intravenous tacrolimus therapy can rapidly induce remission in refractory ulcerative colitis

T. Fujii1, M. Naganuma2, E. Saito1, M. Nagahori1, K. Ohtsuka1, M. Watanabe1, 1Tokyo Medical and Dental University, Gastroenterology and Hepatology, Tokyo, Japan, 2Keio University School of Medicine, Gastroenterology, Tokyo, Japan

Background

Oral tacrolimus therapy has been reported to be effective for refractory ulcerative colitis (UC). Some reviews demonstrated that tacrolimus is superior to ciclosporin A (CsA) in improving graft survival and preventing acute rejection after transplantation. But indeed, some severely active UC patients treated with oral tacrolimus couldn't avoid total colectomy. We thought that it takes long time to achieve high trough concentration by oral administration so the treatment doesn't have effect rapidly and cannot arrest the disease progress. There has been no report to prospectively evaluate the efficacy of tacrolimus intravenous therapy in refractory ulcerative colitis.

Methods

To evaluate the usefulness of intravenous tacrolimus in refractory ulcerative colitis, 23 patients with refractory moderately/severely active UC (steroid-refractory, n = 15; steroid-dependent, n = 8) were enrolled. Tacrolimus (0.025 mg/kg body weight per a day) was initially administered intravenously with serum levels of 10–17 ng/mL for 7 days and later switched to the oral formulation. Clinical activity index (CAI) score and Rachmilewitz's endoscopic index (EI) at 2 and 12 weeks after tacrolimus initiation was prospectively evaluated. Mean duration between administration of tacrolimus and reaching the high concentration level (>10 mg/mL) in intravenous tacrolimus group was also assessed.

Results

Eighteen patients (78%) experienced a clinical and laboratory response and 12 (52%) went into remission in 2 weeks. The median CAI decreased from 13.5±0.50 at initiation to 6.2±0.77 after 2 weeks of treatment. The median EI decreased from 10.4±0.30 at initiation to 5.9±0.41 after 2 weeks of treatment and 1.75±0.51 after 12 weeks of treatment. Serum tacrolimus concentration was achieved at high level in 24 hours intravenous tacrolimus group although previous multicenter study indicated that 5.0 days was needed to achieve at same level in oral tacrolimus group (Naganuma et al, J Gatroenterol 2011). Intravenous tacrolimus therapy was well tolerated, with only minor side effects.

Conclusion

Intravenous tacrolimus therapy produces rapid rise of serum concentration and the therapy is safe and effective for refractory UC patients. It may be useful as salvage therapy to avoid surgery.