Abstract
We examined the efficacy and safety of tacrolimus used in combination with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with insufficient response to treatment by one or more DMARDs. Thirty eight patients(male: 8, female: 30) who had active RA at baseline despite treatment with DMARDs were administered 1-3 (mean 1.4) mg tacrolimus daily for 12 weeks while continuing to receive DMARDs at the existing stable dosage. The patients’ age was 60±15 years. The number of patients who continued to receive methotrexate, salazosulfapyridine or bucillamine was 27, 28 and 20, respectively. Disease activity was evaluated by disease activity score 28 (DAS28). Good response and moderate response in DAS28 improvement were achieved in 12 patients (32%) and 13 patients (34%), respectively. The mean DAS28 decreased from 4.3±0.8 to 3.1±1.1 (P＜0.01) after 12 weeks of treatment. In high disease activity patients (n＝7), DAS28 was markedly improved from 5.4±0.4 to 3.4±1.4 (P＜0.01). Tender joint count was rapidly decreased, although C-reactive protein and swollen joint count were slowly reduced. Two patients discontinued tacrolimus treatment by reason of adverse Events (nausea, loss of appetite). The mean plasma creatinine was slightly increased (0.63±0.23 to 0.65±0.23 mg/dl), but the increase was not significant. These data show that tacrolimus combination therapy with DMARDs is efficacious and safe in refractory RA patients.
