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Efficacy and Safety of Tacrolimus (FK506) in Treatment of Rheumatoid Arthritis: A Randomized, Double Blind, Placebo Controlled Dose-Finding Study
HIROBUMI KONDO, TORU ABE, HIROSHI HASHIMOTO, SHOJI UCHIDA, SHOICHIRO IRIMAJIRI, MASAKO HARA, and SACHIKO SUGAWARA
ABSTRACT.
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 (£ 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. (J Rheumatol 2004; 31:243-51) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Japanese Tacrolimus (FK506) RA Study Group, Kitasato University School of Medicine, Kanagawa, Japan. H. Kondo, MD, PhD, Department of Internal Medicine, Kitasato University School of Medicine; T. Abe, MD, PhD, Saitama Medical Center, Saitama Medical School; H. Hashimoto, MD, PhD, Juntendo University Hospital; S. Uchida, MD, PhD, Uchida Clinic for Rheumatic Diseases; S. Irimajiri, MD, PhD, Department of Internal Medicine, Keio University Hospital; M. Hara, MD, PhD, Institute of Rheumatology, Tokyo Women's Medical University; S. Sugawara MD, PhD, Department of Orthopedics, Tokyo Women's Medical University Daini Hospital. Address reprint requests to Prof. H. Kondo, Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa 228-8555, Japan. E-mail: kondo@med.kitasato-u.ac.jp Submitted May 23, 2002; revision accepted July 14, 2003. |