A Study is to Assess Efficacy and Safety of Tacrolimus in Active Rheumatoid Arthritis Patients Who Showed Unsuccessful Response to Existing Disease Modifying Antirheumatic Drugs (DMARDs) (TREASURE)

• ACR50 response rates at month 6 [ Time Frame: Baseline and at month 6 ] [ Designated as safety issue: No ]
  ACR50 is 50% improvement in ACR (American College of Rheumatology) core set
• ACR70 response rates at month 6 [ Time Frame: Baseline and at month 6 ] [ Designated as safety issue: No ]
  ACR70 is 70% improvement in ACR (American College of Rheumatology) core set
• Change in DAS28 from baseline to 6 months [ Time Frame: Baseline and at month 6 ] [ Designated as safety issue: No ]
  DAS (Disease Activity Score in Rheumatoid Arthritis)
• Change in bone loss rate from baseline to 6 months [ Time Frame: Baseline and at month 6 ] [ Designated as safety issue: No ]
  comparative factors for bone loss rate: bone mineral densitometry [BMD], bone turnover marker test
• Safety assessed by the incidence of adverse events, vital signs and lab-tests [ Time Frame: For 6 months ] [ Designated as safety issue: No ]

This study is to assess efficacy and safety of tacrolimus in active rheumatoid arthritis patients who showed unsuccessful response to existing DMARDs.

Inclusion Criteria:

• Subjects who have rheumatoid arthritis for 6 months or longer based on American College of Rheumatology (ACR) diagnostic criteria
• Subjects who used more than 1 Disease Modifying Antirheumatic Drug (DMARD) including MTX (methotrexate) for 6 months or longer
• Subjects with ESR (erythrocyte sedimentation rate) ≥ 28mm/h or CRP (C-reactive protein)≥ 1.0 mg/dL
• Subjects with ≥ 3 swollen joints out of 66 joints assessed
• Subjects with ≥ 6 tender joints out of 68 joints assessed
• Subjects with BMD (bone mineral densitometry) ≤ -3.0

Exclusion Criteria:

• Pregnant or nursing women, or subjects who plan to become pregnant within 6 months or whose screening test results show pregnancy cannot be ruled out
• Subjects with previous experience of tacrolimus (excluding external preparations)
• Subjects with renal dysfunction or with serum creatinin > 1.4 mg/dL at screening
• Following subjects with hepatic dysfunction: viral infection, non-viral infection, hepatic cirrhosis, and Serum Glutamic Oxaloacetic Transaminase / Serum Glutamic Pyruvic Transaminase (SGOT/SGPT) exceeding twice the upper limit of normal at screening
• Subjects with pancreatitis, uncontrolled diabetes or complication(s) or with HbA1c > 6.4% at screening
• Subjects complicated with hyperkalemia or with serum potassium level >5.5 mEq/L at screening
• Subjects with history of heart disease (ischemic heart disease, arrhythmia requiring treatment, and heart failure), etc or complications
• Subjects complicated with severe respiratory disease and infection
• Subjects with history of malignant tumor or complication(s) (However, the subjects who are considered to have no risk of recurrence with malignant tumor untreated for 5 years or longer can enter the study. The subjects who succeeded in treatment for basal cell or squamous cell carcinoma of skin can also enter the study.)
• Subjects who were treated with other investigational product(s) within 3 months before screening
• Other subjects who are considered ineligible for the study by the investigator