Efficacy and Safety of Tacrolimus Therapy for Active Ulcerative Colitis; A Systematic Review and Meta-analysis

Komaki, Yuga
Komaki, Fukiko
Ido, Akio
Sakuraba, Atsushi

^a Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA,
^b Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Corresponding author: Atsushi Sakuraba, MD, PhD, Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, 5841 S. Maryland Ave. MC 4076, Chicago, IL 60637, USA. Tel: 773-834-0687; fax: 773-834-1029; email: [email protected]

Received August 8, 2015

Received in revised form October 26, 2015

Accepted November 12, 2015

Journal of Crohn’s and Colitis (ecco-jcc) 10(4):p 484-494, April 2016. | DOI: 10.1093/ecco-jcc/jjv221

Background:

Approximately 25% of patients with ulcerative colitis [UC] experience a severe flare requiring steroid therapy to avoid colectomy. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus as a rescue therapy for active UC.

Methods:

Electronic databases were searched for relevant studies assessing the efficacy of tacrolimus for active UC. Outcomes included short- and long-term clinical response, colectomy free rates, and rate of adverse events in randomised controlled trials [RCTs] and observational studies.

Results:

Two RCTs comparing high trough concentration [10–15ng/ml] versus placebo [n = 103] and 23 observational studies [n = 831] were identified. Clinical response at 2 weeks was significantly higher with tacrolimus compared with placebo (risk ratio [RR] = 4.61, 95% confidence interval [CI] = 2.09–10.17, p = 0.15 x 10^-3] among RCTs. Rates of clinical response at 1 and 3 months were 0.73 [95% CI = 0.64–0.81] and 0.76 [95% CI = 0.59–0.87], and colectomy-free rates remained high at 1, 3, 6, and 12 months [0.86, 0.84, 0.78, and 0.69, respectively] among observational studies. Among RCTs, adverse events were more frequent compared with placebo [RR = 2.01, 95% CI = 1.20–3.37, p = 0.83 x 10^-2], but there was no difference in severe adverse events [RR = 3.15, 95% CI = 0.14–72.9, p = 0.47]. Severe adverse events were rare among observational studies [0.11, 95% CI = 0.06–0.20].

Conclusions:

In the present meta-analysis, tacrolimus was associated with high clinical response and colectomy-free rates without increased risk of severe adverse events for active UC.