Double‐blind, placebo‐controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid‐refractory ulcerative colitis

@article{Ogata2012DoubleblindPT,
  title={Double‐blind, placebo‐controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid‐refractory ulcerative colitis},
  author={Haruhiko Ogata and Jun Kato and Fumihito Hirai and Nobuyuki Hida and Toshiyuki Matsui and Takayuki Matsumoto and Katsuyoshi Koyanagi and Toshifumi Hibi},
  journal={Inflammatory Bowel Diseases},
  year={2012},
  volume={18},
  pages={803–808}
}
Background: We report a multicenter study of oral tacrolimus (FK506) therapy in steroid‐refractory ulcerative colitis (UC). Methods: In a placebo‐controlled, double‐blind study, 62 patients with steroid‐refractory, moderate‐to‐severe UC were randomized into either a tacrolimus group or a placebo for 2 weeks. Patients were evaluated using the Disease Activity Index (DAI). As an entry criterion, patients had to have a total DAI score of 6 or more as well as a mucosal appearance subscore of 2 or 3… 

Figures and Tables from this paper

Commentary: short‐term efficacy of tacrolimus in steroid‐refractory ulcerative colitis
  • J. Landy, A. Hart
  • Medicine, Biology
    Alimentary pharmacology & therapeutics
  • 2013
TLDR
A large retrospective study conducted across three centres of 130 patients with moderate to severe UC treated with tacrolimus provides an evaluation of a large group of patients with steroidrefractory UC treatedWith promising short-term outcomes, although longer term outcomes with tacolimus in UC remain unclear.
Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis.
TLDR
Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC and shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation.
Pooled analysis of the comparative efficacy between tacrolimus and infliximab for ulcerative colitis
TLDR
A meta-analysis suggested that both tacrolimus and IFX appeared to be effective and safe for the rescue therapy of moderate-to-severe active UC and steroid-refractory UC.
Comparison of the therapeutic efficacy and safety between tacrolimus and infliximab for moderate-to-severe ulcerative colitis: a single center experience
TLDR
Tac and IFX may be equally efficacious for the induction and maintenance of remission in patients with UC while minor adverse events are more frequent with the former treatment.
Tacrolimus as rescue therapy for steroid-dependent/steroid-refractory ulcerative colitis: Experience from tertiary referral center in India
TLDR
Tacrolimus is effective in inducing a clinical response in 56% of patients with SDUC and SRUC and may be considered first-line therapy for SDUC/SRUC in view of its low cost and safety profile.
The efficacy of oral tacrolimus in patients with moderate/severe ulcerative colitis not receiving concomitant corticosteroid therapy.
TLDR
Oral tacrolimus is a safe and effective therapy for the treatment of moderate to severe UC in patients not receiving concomitant treatment with systemic steroids and may represent a top-down or accelerated step-up treatment option for patients with moderate tosevere UC.
Medium to long-term efficacy and safety of oral tacrolimus in moderate to severe steroid refractory ulcerative colitis.
TLDR
Assessment of the medium to long-term efficacy and safety of oral tacrolimus in patients with moderate to severe ulcerative colitis refractory to steroids found no significant improvement in prognosis.
Oral Tacrolimus for the Treatment of Refractory Inflammatory Bowel Disease in the Biologic Era
TLDR
Tacrolimus is able to induce a clinical response in a third and remission in a fifth of medically refractory patients with inflammatory bowel disease at 1 year, suggesting a 90-day therapeutic trial is worthwhile in difficult to treat patients.
...
...

References

SHOWING 1-10 OF 15 REFERENCES
A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis
TLDR
The findings demonstrate dose dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory UC and the optimal target range appears to be 10–15 ng/ml in terms of efficacy with two week therapy.
Response of Refractory Colitis to Intravenous or Oral Tacrolimus (FK506)
TLDR
FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration and the most frequent adverse events included tremor, hyperglycemia, hypertension, and infection.
Infliximab for induction and maintenance therapy for ulcerative colitis.
TLDR
Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.
Steroid-unresponsive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus (FK506)
TLDR
Tacrolimus induced rapid remission in steroid resistant inflammatory bowel disease in the majority of cases and appears to be an effective treatment modality that may be superior to cyclosporine with respect to maintenance of remission.
Tacrolimus Therapy as an Alternative to Thiopurines for Maintaining Remission in Patients With Refractory Ulcerative Colitis
TLDR
Maintenance therapy with tacrolimus for patients with UC could be considered an alternative to thiopurine therapy in patients with refractory UC.
The use of traditional and newer calcineurin inhibitors in inflammatory bowel disease
TLDR
The use of higher initial doses of tacrolimus ensured that patients achieved their target levels of calcineurin inhibitors, and further studies will be needed to elucidate the efficacy of top-down therapy with tacolimus in patients with UC.
Rapid endoscopic improvement is important for 1-year avoidance of colectomy but not for the long-term prognosis in cyclosporine A treatment for ulcerative colitis
TLDR
Although CSA can exert high initial efficacy for severe attacks of UC, >50% of patients who relapse require a colectomy, and treatment of severe UC with CSA requires consideration of both initial remission and long-term maintenance as management goals.
Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.
TLDR
It is concluded that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis.
Effect of oral tacrolimus (FK 506) on steroid‐refractory moderate/severe ulcerative colitis
TLDR
Oral tacrolimus (FK 506) was investigated as an alternative drug that can be administered orally for Steroid refractory ulcerative colitis to avoid colectomy.
Novel endoscopic activity index is useful for choosing treatment in severe active ulcerative colitis patients
TLDR
The endoscopic activity index (EAI) is equivalent to other endoscopic indices and relatively more useful in choosing a treatment for patients with severe UC.
...
...