A CLINICAL-TRIAL OF FK506 IN REFRACTORY UVEITIS

We performed a clinical open trial to evaluate the efficacy and the ad verse side effects of a single therapy with FK506 in refractory uveiti s as a multicenter study in Japan. Fifty-three patients (41 patients w ith Behcet's disease, five with Vogt-Koyanagi-Harada disease, four wit h idiopathic retinal vasculitis, and three with other forms of uveitis ) were enrolled in the study. FK506 was given orally for 12 weeks. Tre atment with FK506 exhibited therapeutic effects in a dosage-dependent manner: the effectiveness was 38% in patients treated with an initial dosage of 0.05 mg/kg of body weight per day, 60% with 0.10 mg/kg of bo dy weight per day, 83% with 0.15 mg/kg of body weight per day, and 79% with 0.20 mg/kg of body weight per day. Overall efficacy with dosage adjustment when needed was 76.5% at the conclusion of the study at the end of the 12th week. The FK506 therapy induced a variety of adverse side effects, the incidence of which depended on the dosage. The major side effects were renal impairment (28.3%, 15 of 53 patients), neurol ogic symptoms (20.8%, 11 of 53 patients), gastrointestinal symptoms (1 8.9%, ten of 53 patients), and hyperglycemia (13.2%, seven of 53 patie nts). The trough level of FK506 in the whole blood correlated with bot h the efficacy of the therapy and with the incidence of adverse effect s. It is recommended to maintain the trough level between 15 and 25 ng /ml. On the basis of these results, a daily dosage of 0.10 to 0.15 mg/ kg of body weight per day was suggested as an appropriate therapeutic dosage for refractory uveitis.