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Tacrolimus appears to be at least comparable to ciclosporin in refractory ulcerative colitis in terms of tolerability and efficacy but the oral route of administration and reliability of drug levels are advantageous
Tacrolimus is a new calcineurin inhibitor widely used in transplantation medicine. Similar to ciclosporin, tacrolimus inhibits the calmodulin sensitive serine phosphatase calcineurin, thereby reducing NF-AT activation. In this issue of Gut, Ogata and colleagues1 present the first randomised controlled trial of tacrolimus in patients with “refractory” ulcerative colitis (see page 1255). Two tacrolimus arms with low and high trough levels were compared with a placebo group. Oral dosing was adjusted to trough levels by an external board to secure blinding. The primary end point was the proportion of patients with improvement after two weeks based on a disease activity index (DAI) score, a composite of clinical and endoscopic findings, with a range of 0–12 points. Sixty patients were included in the efficacy analysis, of whom only 15 had been “steroid resistant”. Improvement (decrease in DAI score by ⩾4) was achieved in 68%, 38%, and 10% in the high trough, low trough level, and placebo groups, respectively. Remission (DAI score ⩽2) was achieved in 20%, 11%, and 6%, respectively. Open label tacrolimus extension for another 10 weeks in 58 patients yielded an improvement in 55% and remission in 29%. Endoscopic healing was achieved in 73% and a steroid taper was possible in both steroid resistant and dependent cases. Adverse events were tolerable, with a case of severe viral gastroenteritis and one with acinetobacter sepsis but no mortality.
Although this trial is well designed and results are convincing, there are several limitations. The randomised part of the study was ultrashort, with only two weeks’ duration, possibly for ethical reasons. However, the previous uncontrolled trials with longer …
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