Rheumatoid Arthritis Memory B Cells and Abatacept

Inclusion Criteria: * Signed Written Informed Consent 1\. Subject is willing to participate in the study and has signed the informed consent. * Target Population 1. Men or women (not nursing or pregnant) over 18 years old who have active Rheumatoid Arthritis, defined as symptoms of Rheumatoid Arthritis prior to screening and have satisfied the American College of Rheumatology/ European League Against Rheumatism 2010 criteria for the classification of Rheumatoid Arthritis prior to signing t the informed consent. 2. Subjects must have a Disease Activity Score 28-joint count C reactive protein (CRP) or Clinical Disease Activity Index (CDAI) assessment at screening and have at least 3 tender and at least 3 swollen joints (excluding distal interphalangeal joints) at screening and at Day 1. Patients must have at least moderate disease activity {CDAI\>16); Disease Activity Score and C-reactive protein test (DAS28CRP (\>4.0 )\]. 3. Subjects must be naive to biologic Disease-modifying antirheumatic drugs (DMARDs) 4. Subjects must be naive to targeted synthetic DMARDs such as tofacitinib, baricitinib, and investigational therapies for RA. 5. Subjects receiving oral corticosteroids must be on a stable dose and at the equivalent of 10 mg prednisone daily for at least 4 weeks. Subjects may not receive an intravenous (IV), intramuscular (IM) or intra-arterial (IA) administration of a corticosteroid within 4 weeks prior to screening visit or initiation of therapy 6. Patients with prior (including discontinued) therapy with Methotrexate and/or Hydroxychloroquine are permitted as long as they meet other inclusionary criteria. 7. Subjects must have a DAS28CRP and Clinical Disease Activity Index (CDAI) at screening and have at least 3 tender and at least 3 swollen joints (excluding distal interphalangeal joints) at screening and at Day 1. * Age and Reproductive Status 1. Men and women, age's 18 years (or age of majority) 2. Women of childbearing potential (WOCBP) must have a negative serum or urine 3. pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 4. 24 hours prior to the start of study drug. 5. Women must not be breastfeeding and must agree not to breastfeed during the study and for 100 days thereafter 6. WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of study drug (70 days) plus 30 days (duration of ovulatory cycle) for a total of 100 days post-treatment completion. 7. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug, plus 5 half- lives of the study drug (70 days) plus 90 days (duration of sperm turnover) for a total of 160 days post-treatment completion. 8. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However they must still undergo pregnancy testing as described in this section. Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 9. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of \< 1% when used consistently and correctly. 10. At a minimum, subjects must agree to use one highly effective method of contraception as listed below. * Highly effective methods of contraception 1. Highly effective methods of contraception have a failure rate of \< 1% when used consistently and correctly. WOCBP and female partners of male subjects, who are WOCBP, are expected to use one of the highly effective methods of contraception listed below. Male subjects must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. 1. Progestogen only hormonal contraception associated with inhibition of ovulation. 2. Hormonal methods of contraception including oral contraceptive pills containing estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena 3. Nonhormonal IUDs, such as ParaGard 4. Bilateral Tubal occlusion 5. Vasectomized partner with documented azoospermia 90 days after procedure 2. Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success. 3. Intrauterine hormone-releasing system (IUS) 4. Complete abstinence- Complete abstinence is defined as the complete avoidance of heterosexual intercourse 1. complete abstinence is an acceptable form of contraception for all study drugs and must be used throughout the duration of the study treatment (plus 5 half-lives of the investigational drug plus 30 days). 2. It is not necessary to use any other method of contraception when complete abstinence is elected. 3. Subjects who choose complete abstinence must continue to have pregnancy tests 4. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence. 5. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. * Unacceptable methods of contraception 1. Periodic abstinence (calendar, symptothermal, post-ovulation methods) 2. Withdrawal (coitus interruptus) 3. Spermicide only 4. Lactation amenorrhea method (LAM) Exclusion Criteria: * Target Disease Exceptions 1. Subjects with autoimmune disease other than RA \[e.g., psoriasis, systemic lupus erythematosus (SLE), vasculitis, seronegative spondyloarthritis, Inflammatory Bowel Disease, Sjogren's syndrome\] or currently active fibromyalgia. 2. Prior history of or current inflammatory joint disease other than RA (such as psoriatic arthritis, gout, reactive arthritis, Lyme disease). * Medical History and Concurrent Diseases 1.Subjects at risk for tuberculosis (TB) defined as follows: 1. Current clinical, radiographic or laboratory evidence of active TB. Chest x-rays (posterior anterior and lateral) obtained within the 3 months prior to obtaining written informed consent will be permitted but the images must be available and reviewed by the investigator. TB testing (IFN-gamma release assay or PPD) performed in the past month prior to Screening will be accepted; however, a copy of the report must be placed in the subject binder. 2. A history of active TB 3. Subjects with a positive TB screening test indicative of latent TB will not be eligible for the study unless they: 4. Have no evidence of current TB based on chest x-ray performed And they are actively being treated for TB or the site has documentation of successful prior treatment of latent TB. Treatment regimens should be dictated by local guidelines as long as the treatment dose and duration meet or exceed local health authority guidelines. 2.Subjects with recent acute infection defined as: <!-- --> 1. Any acute infection within 60 days prior to randomization that required hospitalization or treatment with parenteral antibiotics. 2. Any acute infection within 30 days prior to randomization that required oral antimicrobial or antiviral therapy. 3. Subjects with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis etc.). 4. Subjects with any history of infection of a joint prosthesis or artificial joint. 5\. Subjects who have a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis). 6. Subjects with history of recurrent herpes zoster (more than 1 episode) or disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster will be excluded. Symptoms of herpes zoster or herpes simplex must have resolved more than 60 days prior to screening. 7. Subjects with history of Human Immunodeficiency Virus (HIV) infection or who tested positive for HIV 8. Subjects with history of primary immunodeficiency <!-- --> 1. Subjects who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Subjects who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations. 10. Current clinical findings or a history of a demyelinating disorder 11. New York Heart Association (NYHA) Class III or IV heart failure 12. Any previous or current medical conditions that are warnings against the use of TNF inhibitor agents. 13. Current clinical findings of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, endocrine, neurological, or cerebral disease including severe and uncontrolled infections, such as sepsis and opportunistic infections. Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study. 14. Subjects who have received any live vaccines within 3 months of the study drug administration or are scheduled to receive live vaccines during the study. Study subjects should not be administered a live virus vaccine for a minimum of 3 months f following the last dose of study medication. Subjects who are in close contact with others who have received a live vaccine may be enrolled at the investigator's discretion. 15. Subjects who have undergone a major surgical procedure within the 60 days prior to randomization. 16. Subjects for whom 5 or more joints cannot be assessed for tenderness or swelling (i.e. due to surgery, fusion, amputation, etc.). 17.Subjects who are prisoners, or compulsory detained.