We performed a prospective study to assess the optimal blood concentration of tacrolimus in Japanese patients with rheumatoid arthritis (RA). The dose of tacrolimus (1-3mg/day) was administered orally once daily after the evening meal, and the blood concentration of tacrolimus 12 hr after administration was quantified. A total of 23 patients were enrolled. Clinical efficacy was assessed using the Disease Activity Score in 28 joints and European League Against Rheumatism (EULAR) response criteria at each outpatient visit during months 1-6. The ratio of patients who showed a moderate or good response was 47.8% (11/23). The mean blood concentrations of tacrolimus in EULAR responders and EULAR non-responders were 5.5±3.6 (mean±S.D.) and 3.1±1.9 ng/ml, respectively (p = 0.069). Interestingly, although tacrolimus had lower mean blood concentrations (< 5ng/ml) compared with transplant fields (10-20 ng/ml), six (35.3%) of 17 patients showed sufficient response to tacrolimus. In addition, in five patients, tacrolimus was co-administered with methotrexate (MTX). On the other hand, the mean blood concentrations of tacrolimus in patients who did or did not develop adverse events were 4.8±4.4 (n = 8) and 4.0±2.1 (n = 15) ng/ml, respectively (p = 0.624). We failed to clear the optimal blood concentration of tacrolimus in RA patients, but one of the most remarkable findings was the observation that patients in whom tacrolimus was combined with MTX reached a positive response at much lower tacrolimus concentrations compared to patients not co-treated with MTX.
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