Tacrolimus (FK506) for induction of remission in refractory ulcerative colitis.

Background: There are a limited number of treatment options for patients with refractory ulcerative colitis. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that tacrolimus may be effective treatment for ulcerative colitis.

Objectives: This review aims to evaluate the efficacy of tacrolimus for induction of remission in patients with corticosteroid refractory ulcerative colitis.

Search Strategy: MEDLINE (PubMed), The Cochrane Central Register of Controlled Trials, the IBD/FBD review group specialized register and the ISI-Research Institute were searched (January 1997 to November 2007) to identify relevant studies all randomized trials.

Selection Criteria: Each author independently reviewed potentially relevant studies to determine eligibility based on the pre-specified criteria.

Data Collection And Analysis: A data extraction form was developed and used to extract data from included studies. Two authors independently extracted data. Data were analyzed using Review Manager (RevMan 4.2.9). The primary outcomes were induction of remission and clinical improvement, as defined by the studies and expressed as a percentage of the patients randomized (intention to treat analysis).

Main Results: One randomized controlled trial comparing high target serum concentration and low target serum concentration tacrolimus versus placebo was identified and included in the review. Clinical remission was observed in 19% (4/21) of patients in the high target serum concentration group, in 9% (2/22) in the low target serum concentration group and in 5% (1/20) in the placebo group (OR 2.27; 95% CI 0.35 to 14.75). A statistically significant benefit for clinical improvement at two weeks was observed. Clinical improvement was observed in 62% (13/21) of patients in the high target serum concentration group, in 36% (8/22) in the low target serum concentration group and in 10% (2/20) in the placebo group (OR 8.66; 95% CI 1.79 to 42.00; RD 0.39; 95% CI 0.20 to 0.59; NNT = 3). Patients in the high serum target concentration group were significantly more likely than placebo patients to experience adverse events related to treatment (P = 0.043). Finger tremor (n = 6) was the most common adverse event in the tacrolimus group. Other adverse events included: gastroenteritis, sepsis, sleepiness, hot flush, headache, queasiness and stomach discomfort.

Authors' Conclusions: Tacrolimus may be effective for short-term clinical improvement in patients with refractory ulcerative colitis. However, these results should be interpreted with caution due to the small number of patients enrolled in the trial and other study limitations. Insufficient treatment and follow-up intervals prevent any conclusions with regard to long term safety and efficacy. The use of tacrolimus in the clinical setting requires careful consideration of risks versus benefits as well as close monitoring for adverse events. More data from well designed and controlled studies are needed to determine the long-term efficacy and safety of tacrolimus.