Immunosuppressive therapy with intravenous ciclosporin is an alternative treatment option to total colectomy for patients with ulcerative colitis.
However, the benefits of oral administration of tacrolimus are not well defined and are based on reports of several uncontrolled studies.
Dr Ogata and colleagues from Japan randomly assigned 21 patients with refractory active ulcerative colitis to a high trough concentration group.
The team randomized 22 patients to low trough concentration, and 20 patients to placebo group.
Patients received an initial oral dose of 0.05 mg/kg tacrolimus or placebo twice daily.
|Optimal target range is 10 to15 ng/ml in terms of efficacy with 2 week therapy|
The investigative team evaluated efficacy in 60 patients based on a disease activity index score.
The investigators evaluated 58 patients who had additional treatment with tacrolimus.
The team assessed for efficacy in a 10 week open label extension.
An improvement in disease activity index score was observed for 68% of cases in the high dose group compared with 10% in the placebo group.
In the high dose group, the team found that 20% of patients had clinical remission and 79% had mucosal healing.
In the open label extension, 55% of all patients had an improved disease activity index score at week 10.
The team observed that the mean dose of prednisolone was reduced from 20 mg/day at study entry to 8 mg/day at week 10.
The incidence of side effects in the high dose group was significantly higher than that of the placebo group.
The investigators observed that the most common event was mild finger tremor.
Dr Ogata's team concludes, “Our findings demonstrate dose dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory ulcerative colitis.”
“The optimal target range appears to be 10 to 15 ng/ml in terms of efficacy with 2 week therapy.”