Effectiveness and Safety of Tacrolimus in Patients with Active Rheumatoid Arthritis with Inadequate Response to Disease-modifying Anti-rheumatic Drugs: The TREASURE Study

Objective. Evaluate effectiveness/safety of tacrolimus in patients in Korea with active rheumatoid arthritis (RA) and unsuccessful response to disease-modifying anti-rheumatic drugs (DMARDs). Methods. Open-label, single-arm, non-comparative, 24-week, Phase-IV study in patients with active RA who had taken DMARDs for >6 months. Following a washout period, tacrolimus was initiated (baseline-12 weeks; dose 2 mg/day and 1.5 mg/day in patients aged <= 65 and >65 years, respectively). After 12 weeks, dose could be adjusted (remaining between 1 similar to 3 mg); treatment continued to 24 weeks. Primary endpoint was American College of Rheumatology 20% improvement (ACR20) (baseline-Week 24). Secondary endpoints included ACR50/ACR70 response, disease-activity score in 28 joints (DAS28) erythrocyte sedimentation rate (ESR), number of tender/swollen joints, and bone mineral density (BMD) loss. Adverse events (AEs) were recorded. Results. Overall, 121 patients were analysed. Mean +/- standard deviation tacrolimus dose baseline-Week 24 was 1.81 +/- 0.47 mg/day. After 24 weeks, 64.5%, 39.7%, and 19.0% of patients were ACR20, ACR50, and ACR70 responders, respectively. DAS28-ESR score decreased from 5.5 +/- 0.8 (baseline) to 3.7 +/- 1.5 (Week 24; p<0.0001); number of tender/swollen joints decreased. Between screening and Week 24, change in BMD-T score in lumbar and femur regions was - 0.06 +/- 0.38 (p = 0.1550) and - 0.04 +/- 0.28 (p = 0.0936), respectively, with no significant change in International Society for Clinical Densitometry classification. Fifty-six (46.3%) patients experienced 93 AEs; 75.3% were mild. No unexpected safety signals identified. Conclusion. Tacrolimus therapy was associated with a high proportion of ACR responders, and improved DAS28-ESR score and physical joint function during the study. Tacrolimus may be a suitable therapy for DMARD-resistant patients with RA.