The purpose of this study is to access the efficacy and safety of Mizoribine 150mg qid and 50mg tid in active rheumatoid arthritis patients unsuccessfully treated with disease-modifying antirheumatic drug.

1. EULAR Response after 24weeks of treatment
2. EULAR Response after 12weeks of treatment
3. DAS28 value change
4. KHAQ-20 value change

Inclusion Criteria:

• Male or female aged from 20 to 80 years old
• Signed and dated informed consent document indicating that the patient
• Patients must have a diagnosis of Rheumatoid Arthritis(RA) of at least 3months duration as defined by the 2010 American College of Rheumatology(ACR) Classification criteria.
• Patients should have a Disease Activity Score 28 greater than or equal to 3.2 (DAS28 ≥ 3.2) and have received treatment with more than 1 kind of disease-modifying antirheumatic drug(including MTX).
• ESR≥28mm/h or CRP≥1.0mg/dl at screening.

Exclusion Criteria

• At screening, patients have laboratory result as defined by : white blood cell ≤ 3,000/mm3

  , Hemoglobin < 8.5 g/dL, Platelet count < 100,000/mm3, Serum creatinine > 2.0 mg/dL, Aspartic Acid Transaminase/Alanine Transaminase ≥ 2*upper limit of normal , Uric acid ≥ 1.5*upper limit of normal

• Patient must not have bleeding disorder or taking anticoagulant. (But, lt is allowed to take 100mg/day of Asprin)

• Patients with a history of operation on index knee joint which could have influence on the result and need to have surgery as determined by investigator.

• Patients have severe infection, including moderate respiratory disease and have received treatment with systemic antibiotics within 2 weeks.

• Patients have cardiovascular disease or associated disease which is not controlled.

• Patients have a history of malignancy within 5years. (But, basal cell or squamous cell carcinoma or carcinoma in situ of the uterine cervix have been treated is allowed)

• Patients have hypersensitivity reaction on this drug.

• Patients on any other clinical trial or experimental treatment in the past 3months.

• Female patients who are breast feeding, pregnant or plan to become pregnant during the trial or for two months following study termination.

• Not allowable medication recorded below ; Intra-articular injections within weeks at baseline visit, Patients taking oral steroid over 10mg /day or using new treatment or changing dosage within 4weeks at baseline visit, Using new nonsteroidal antiinflammatory drug within 4 weeks or changing nonsteroidal antiinflammatory drug dosage within 2 weeks at baseline visit.

• Having experience of use biologic agent, immunosuppressant, cytostatic preparations within 8weeks at baseline visit. (But, Rituximab is not allowed within 6months)

• Start to treatment new disease-modifying antirheumatic drug or need to change dosage of disease-modifying antirheumatic drug which is taking on the trial. (Leflunomide(ARAVA®) is not allowed within 12weeks, But, Cholestyramine is allowed after 48 hours later stopping. if it use three times a day, 8g, for 11days)