Safety of long-term tacrolimus therapy for rheumatoid arthritis: an open-label, uncontrolled study in non-elderly patients

In this study we focused on the safety of long-term tacrolimus therapy in non-elderly patients with rheumatoid arthritis who were treated with tacrolimus or mizoribine in a previous double-blind study. The patients received oral tacrolimus at a dose <= 3 mg once daily for 76 weeks. The safety analysis population included 115 patients aged 20-64 years. Adverse drug reactions presented as symptomatic events in 39 patients (33.9%), laboratory abnormalities in 38 patients (33.0%), and infections in 19 patients (16.5%). The major reactions were gastrointestinal disorders and hypertension as symptomatic events, increases of creatinine, urinary N-acetylb-D-glucosamidase and hemoglobin A(1C) as laboratory abnormalities, and the common cold syndrome as infections. After 76 weeks of tacrolimus treatment, the ACR20 response rates of patients who had also received tacrolimus during the preceding double-blind study was 61.5% (compared with the status at baseline in the preceding study). The corresponding response rate for patients who had previously received mizoribine was 66.0%. The mean blood concentration of tacrolimus was 3.8-4.8 ng/mL. In conclusion, safety profiles of tacrolimus treatment for long-term seems to be similar to those of previous studies in patients with rheumatoid arthritis.