RT Journal Article
SR Electronic
T1 Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 243
OP 251
VO 31
IS 2
A1 Hirobumi Kondo
A1 Toru Abe
A1 Hiroshi Hashimoto
A1 Shoji Uchida
A1 Shoichiro Irimajiri
A1 Masako Hara
A1 Sachiko Sugawara
YR 2004
UL http://www.jrheum.org/content/31/2/243.abstract
AB OBJECTIVE: To evaluate the efficacy and safety of tacrolimus (FK506) in patients with active rheumatoid arthritis (RA) exhibiting resistance to disease modifying antirheumatic drug (DMARD) therapy, and to determine the optimal dosage. METHODS: A total of 212 patients with DMARD-resistant RA were enrolled in this double blind, multicenter, randomized, placebo controlled study and allocated to 3 groups. Patients were administered tacrolimus at a dosage of 1.5 mg/day (68 patients) or 3 mg/day (70 patients), or placebo (74 patients), for 16 weeks. They were allowed to continue taking prednisolone (< or = 5 mg/day) and/or one nonsteroidal antiinflammatory drug (NSAID) during the study. Clinical assessment was based on the American College of Rheumatology (ACR) 20% criteria. RESULTS: ACR 20% response rates were higher in both tacrolimus groups (3 mg: 48.3%; 1.5 mg: 24.6%) than in the placebo group (14.1%), with the rate in the 3 mg group significantly higher. There were no significant differences between the tacrolimus groups and placebo group in the incidence of adverse events. The main adverse events in the tacrolimus groups, especially in the 3 mg group, were renal function abnormalities and gastrointestinal symptoms. However, no significant differences were observed among the 3 groups in the incidence of any adverse event except decrease in serum Mg level. CONCLUSION: Our findings demonstrate excellent dose-dependent efficacy of tacrolimus in patients with DMARD-resistant RA and strongly suggest the usefulness of tacrolimus for treatment of RA. The optimal dosage appears to be 3 mg/day in terms of efficacy and safety.