J Rheum Dis.  2019 Jan;26(1):20-30. 10.4078/jrd.2019.26.1.20.

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

• Sheen DH
• Hong SJ
• Lee SH
• Lee HS
• Chung WT
• Jiang H
• Lee S
• Yoo DH

• KMID: 2442031
• DOI: http://doi.org/10.4078/jrd.2019.26.1.20

Abstract

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.

Keyword

Anti-rheumatic; Bone density; Osteoporosis; Rheumatoid arthritis; Tacrolimus

MeSH Terms

Antirheumatic Agents*
Arthritis, Rheumatoid*
Blood Sedimentation
Bone Density
Classification
Densitometry
Femur
Humans
Joints
Korea
Mass Screening
Osteoporosis
Rheumatology
Tacrolimus*
Antirheumatic Agents
Tacrolimus

Figure

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  Figure 1. Patient flow through the study. AE: adverse event.

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  Figure 2. Proportion of ACR responders at Week 24 in the ITT and PP populations after 24 weeks of treatment with tacrolimus. ACR20, ≥20% improvement in the seven ACR response criteria. ACR50, ≥50% improvement in the seven ACR response criteria. ACR70, ≥70% improvement in the 7 ACR response criteria. ACR: American College of Rheumatology, ITT: intention-to-treat, PP: per-protocol, CI: confidence interval.

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