[A phase II study of FK506 (tacrolimus) on refractory uveitis associated with Behçet's disease and allied conditions]

Abstract

A multicenter open study was conducted to investigate optimum dose schedule of FK506 on refractory uveitis associated with Behçet's disease and allied conditions. Fifty-three patients (41 with Behçet's and 12 with allied conditions) were enrolled in this study. A daily oral dose of FK506 was initially 0.05, 0.1, 0.15 or 0.2 mg/kg, but adjusted in more than half patients during the study based on clinical conditions of patients and/or adverse effects of FK506. The improvement rate of initial daily dose as well as final improvement rate were evaluated in the study. The improvement rate of initial daily dose was increased dose-dependently; 37.5% with 0.05 mg/kg initial daily dose group, 60.0% with 0.1 mg/kg, 91.7% with 0.15 mg/kg and 78.6% with 0.2 mg/kg. The final improvement rate was 76.5%. In patients with Behçet's disease, ocular symptoms improved in 30 (75.0%) of 40 patients evaluable for efficacy and the frequency of ocular attacks was significantly reduced. In eight (66.7%) of 12 patients with Behçet's disease in whom cyclosporin treatment had been failed, their ocular symptoms improved by FK506. Main adverse reactions of FK506 were renal impairment (28.3%), neurologic symptoms (22.6%), gastrointestinal symptoms (20.8%), hypomagnesemia (28.3%), hyperkalemia (13.2%), and hyperglycemia (13.2%. Most of the adverse effects disappeared or ameliorated after FK506 dose reduction or withdrawal from FK506 therapy. It seems that the incidence of the adverse effects depends on the dosage of FK506. The lower dosage (0.05 and 0.1 mg/kg) caused a relatively small number of adverse effects, and the higher dosage (0.15 and 0.2 mg/kg) caused them more frequently. Through level is recommended to maintain between 15-25 ng/ml during early days of treatment based on the safety and efficacy. It is also recommended that a initial daily dose is 0.15 mg/kg on the basis of the efficacy and safety results, and then adjusted based on symptoms of patients and whole blood through level of FK506.