To prospectively evaluate the safety of tacrolimus in active rheumatoid arthritis (RA) in elderly patients with insufficient response to disease-modifying antirheumatic drugs (DMARDs).
Fifty-seven patients aged > or =65 yr with RA for > or =6 months were enrolled in an open-label, non-controlled study. All DMARDs were discontinued and tacrolimus was administered orally once daily after the evening meal for 28 weeks. Tacrolimus, initiated at 1.5 mg/day, was increased to 3 mg/day after 6 weeks if no abnormal changes developed. Existing NSAID and oral corticosteroid (< or =7.5 mg/day prednisolone equivalent) therapy could be continued during the study. Safety was evaluated as clinical symptoms, abnormal changes in laboratory values and the development of infection. Treatment response was determined using the American College of Rheumatology (ACR) criteria for improvement. Whole blood concentrations of tacrolimus 12 h after administration were measured by high-performance liquid chromatography and tandem mass spectrometry.
Clinical adverse events developed in 25 patients (46.3%). Abnormal changes in laboratory values occurred in 25 patients (46.3%). Ten patients (18.5%) developed infection. An ACR20 response was achieved by 50.0% of efficacy-evaluable patients and ACR20 success rates (the proportion of patients achieving ACR20 response and completing the study) was 46.3%. The ACR50 response rate was 18.5% of evaluable patients. Mean blood concentration of tacrolimus was 3.3 and 5.3 ng/ml in patients receiving 1.5 and 3.0 mg daily, respectively. No relationship between its concentration and adverse reactions was observed.
In elderly patients with insufficient response to DMARD therapy, tacrolimus at 1.5-3.0 mg/day is safe and well-tolerated and provides clinical benefit.