J Rheum Dis 2019; 26(1): 20-30  
Effectiveness and Safety of Tacrolimus in Patients with Active Rheumatoid Arthritis with Inadequate Response to Disease-modifying Anti-rheumatic Drugs: The TREASURE Study
Dong Hyuk Sheen1, Seung Jae Hong2, Sang Heon Lee3, Hye Soon Lee4, Won Tae Chung5, Hongsi Jiang6, Sungmin Lee7, Dae Hyun Yoo8
1Division of Rheumatology, Eulji University Hospital, Daejeon, 2Division of Rheumatology, Kyung Hee University Medical Center, Seoul, 3Division of Rheumatology, Konkuk University Medical Center, Seoul, 4Division of Rheumatology, Hanyang University Guri Hospital, Guri, 5Division of Rheumatology, Dong-A University Hospital, Busan, Korea, 6Medical Affairs Asia Oceania, Astellas Pharma, Inc., Singapore, 7Medical Affairs, Astellas Pharma Korea, Inc., 8Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
Correspondence to: Dae Hyun Yoo http://orcid.org/0000-0002-0643-4008
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. E-mail:dhyoo@hanyang.ac.kr
Received: March 30, 2018; Revised: July 28, 2018; Accepted: August 1, 2018; Published online: January 1, 2018.
© Korean College of Rheumatology. All rights reserved.

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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 1~3 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.
Keywords: Anti-rheumatic, Bone density, Osteoporosis, Rheumatoid arthritis, Tacrolimus

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