Abstract
The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus for treating rheumatoid arthritis (RA) patients in clinical practice. Fifty-five active RA patients who had been resistant or intolerant to other disease-modifying antirheumatic drugs were enrolled in this open-label trial. Patients were administered tacrolimus at a dosage of 1, 2 or 3 mg once daily, and followed up for 24 weeks. They were divided into three groups according to their dosage. Efficacy and safety were evaluated utilizing clinical and laboratory findings. Eighty percent of the patients had moderate or high disease activity; 55% were elderly and 53% had complications; 65% of the patients were started on tacrolimus as a monotherapy. Moderate or good response rates were achieved as follows: 38.2% (4 weeks); 41.8% (12 weeks); and 45.6% (24 weeks). Adverse events were observed in seven cases (12.7%). Only one case required hospitalization due to severe hyperglycemia caused by a high tacrolimus concentration (24.2 ng/ml); we suspected a drug interaction in this subject. Mean concentrations were dose-dependent in the 1, 2, and 3 mg/day groups (2.96, 4.29, and 8.32 ng/ml, respectively). Four cases of high concentration (over 10 ng/ml), without any signs or symptoms, were observed in the 3 mg/day group; in these cases, doses were decreased and no severe adverse events occurred. Tacrolimus was found to be both effective and safe in treating active RA patients with complicated backgrounds in clinical practice. Blood concentration measurements and dose adjustments should be performed to prevent severe adverse events in a 3 mg/day group.
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296_2008_833_MOESM1_ESM.pdf
Supplementary Figure 1: Efficacy in each patient according to the initial dose. Changes of DAS28-3CRP after 4, 12 and 24 weeks from baseline in 1, 2, and 3mg/day of TAC groups are shown. Number of patients in each group at 4, 12 and 24 weeks were 7(4W), 35(12W), and 13(24W) in 1mg group; 7(4W), 29(12W), and 11(24W) in 2mg group; and 7(4W), 23(12W), and 9(24W) in 3mg group. Closed circles show each patient and closed bars show mean values. Statistical significance was evaluated by non-repeated measures of ANOVA. (PDF 38 KB)
296_2008_833_MOESM2_ESM.pdf
Supplementary Figure 2: Efficacy in each patient according to combination of DMARDs. Mean value and standard deviation of DAS28-3CRP at 4, 12 and 24 weeks in TAC with no DMARDs, with MTX combination, and with other DMARDs, were shown by black, gray, and white bars. Number of patients in each group at 0, 4, 12 and 24 weeks were 36(0W), 36(4W), 29(12W), and 23(24W) in the TAC with no DMARDs group; 11(0W), 11(4W), 11(12W), and 10(24W) in the MTX combination group; and 9(0W), 9(4W), 8(12W), and 7(24W) in other DMARDs group. Statistical significance was evaluated by non-repeated measures of ANOVA. (PDF 20.6 KB)
296_2008_833_MOESM3_ESM.pdf
Supplementary Table 2: Nomenclature of initial combination of DMARDs with TAC and their number of patients. (PDF 27.5 KB)
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Suzuki, K., Kameda, H., Amano, K. et al. Single center prospective study of tacrolimus efficacy and safety in treatment of rheumatoid arthritis. Rheumatol Int 29, 431–436 (2009). https://doi.org/10.1007/s00296-008-0833-z
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DOI: https://doi.org/10.1007/s00296-008-0833-z