title: Efficacy and Safety of Tacrolimus Therapy for Active Ulcerative Colitis; A Systematic Review and Meta-analysis.
abstract: 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.
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Yuga
authors.initials: Y
authors.lastname: Komaki
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Fukiko
authors.initials: F
authors.lastname: Komaki
authors.affiliation: Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA, asakurab@medicine.bsd.uchicago.edu.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakuraba
mesh_terms: D003093:Colitis, Ulcerative / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Ulcerative colitis; immunosuppressant; meta-analysis; systematic review; tacrolimus