Inclusion Criteria:
1. Male or female, aged 18 to 70, inclusive.
2. Have a diagnosis of RA in agreement with the 2010 ACR classification criteria: Sum of score equal or more than 6/10 in categories A-D including: A, Joint involvement; B, Serology; C, Acute-phase reactant; D, Duration of symptoms.
3. Have established RA \> 6 months of symptoms
4. Have had an inadequate response or documented intolerance to available RA therapies including csDMARDs and TNFi bDMARDs.
5. Current use of csDMARD treatment for RA with at least one of the following: methotrexate (up to 25 mg daily), sulfasalazine (up to 3 g daily), hydroxychloroquine (up to 400mg daily), or leflunomide (up to 20mg daily), or any combination of these agents (with the exception of methotrexate and leflunomide) for at least 3 months, with a stable dose (including route of administration for methotrexate) for at least 6 weeks prior to the screening visit (Visit 0)
6. Have SJC of 4 or more out of 28 at screening and baseline
7. Have TJC of 4 or more out of 28 at screening and baseline
8. CRP greater than upper limit of normal (ULN)
9. Positive for RF and/or anti-CCP antibodies but without extra-articular disease or functional limitations
10. Clinically stable with no significant changes in health status within 2 weeks prior to randomization
11. Stated willingness to comply with all study procedures and availability for the duration of the study
12. Patients must be informed of the investigational nature of this study and give written informed consent in accordance with the institutional and hospital guidelines.
Exclusion Criteria:
1. Infections of hepatitis B, hepatitis C, active or latent tuberculosis, or positive for human immunodeficiency virus (HIV)1 or HIV2
2. Any history of ongoing, significant infections or recent serious infection, i.e., requiring hospitalization and or IV antimicrobial treatment in the 3 months prior to screening.
3. Any active inflammatory diseases other than RA.
4. Serum aminotransferase (ALT or AST) levels \> 2x ULN
5. Inadequate kidney function, defined as an estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73 m2 using Modification of Diet in Renal Disease (MDRD) 4-variable formula
6. Chronic obstructive pulmonary disease or known lung disease except for mild asthma treated with bronchodilators.
7. Any coexistent active major medical diagnosis of clinically significant cardiovascular, neurological psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), or hematological abnormalities that are likely to interfere with patient compliance or study assessments/procedures in the investigators' opinion
8. History of transient ischemic attack
9. History of cerebrovascular accident (stroke)
10. Clinically significant heart disease (New York Heart Association, class III and class IV).
11. Surgery or trauma within 14 days.
12. Pregnant, breastfeeding, or desire to become pregnant or unwilling to practice birth control during participation in the study and for twelve months after completing the study infusion, unless surgically sterilized or postmenopausal during the study.
13. Washout period less than 6 months for rituximab or less than 4 weeks for other bDMARDs.
14. Corticosteroid usage at a high dose (i.e., IV or IM corticosteroids or use of oral prednisone equivalent \>10 mg/day) or not at a stable dose for the treatment of RA or other diseases within 28 days prior to randomization.
15. Known allergies or had a history of allergy to blood products
16. Blood product usage within 50 days (except albumin)
17. Already participating in another interventional clinical trial or participated in another interventional clinical trial within 3 months before screening.
18. Clinical history of malignancy with the exception of adequately treated cervical carcinoma in situ or basal cell carcinomas.
