Impact of Subcutaneous Abatacept in Rheumatoid Arthritis Assessing Inhibition of Structural Damage

Inclusion Criteria: 1. Subjects currently experiencing active moderate to severe RA according to the revised 1987 ACR criteria for the diagnosis of RA at screening. The ESR-based DAS 28 must be equal or greater than 3.2 2. MTX inadequate responders with moderate to severe RA. Subjects currently receiving MTX for at least 12 weeks and who have received MTX at a stable dose (≥15mg/week) for at least 6 weeks prior to treatment (Day 0). They must be biologic drug naive 3. All subjects must receive at least 5 mg oral folic acid weekly. 4. At screening active RA as defined by ≥ 6 swollen joints and ≥ 6 tender joints with erythrocyte sedimentation rate (ESR) ≥ 28 mm/h. 5. Subjects must be seropositive with documented rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti CCP) positivity. If a documented history of RF or anti CCP positivity is not available, RF and anti CCP titers will be obtained at screening 6. MRI evidence of at least one joint with osteitis or erosion attributable to RA as determined by an MRI musculoskeletal radiologist. Any joint of the dominant hand or wrist can be considered with the exception of distal interphalangeal joints of the hands. 7. If subjects are receiving an oral corticosteroid, the dose must be ≤10 mg/day prednisone (or equivalent) and stable for at least 28 days prior to treatment (Day 0). 8. Subjects able and willing to give written informed consent and comply with the requirements of the study protocol. Informed consent must be obtained prior to any study-related procedures. A copy of the signed informed consent form must be given to the subject 9. Subjects must be willing to self-inject or allow a caregiver to administer the subcutaneous injection Exclusion Criteria: 1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization 2. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome). Prior history of or current inflammatory joint disease other than RA (gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis and psoriatic arthritis) 3. Functional class IV as defined by the ACR Classification of Functional Status in RA 4. Current treatment with any traditional DMARDs other than MTX within 4 weeks before the screening visit 5. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening 6. Exposure to any Biologic Response Modifying Agent 7. Intra Articular or parenteral corticosteroids within 6 weeks prior to screening 8. Immunization with live vaccine within 3 months prior to enrollment and a need for a live vaccine during the study 9. Subjects who have a metal device where the use of MRI is contraindicated (e.g.,any type of electronic, mechanical, or magnetic implant; cardiac pacemaker, aneurysm clip; implanted cardioverter defibrillator; or a cochlear implant). Subjects who have a potential ferromagnetic foreign body (metal shavings, metal slivers, other metal objects) for which they have sought medical attention 10. Exclusionary laboratory: Serum creatinine \>2 mg/dL, ALT or AST \> 2.0 x ULN, total bilirubin \> 2.0 x ULN, platelet count \<100 x 109 /L, hemoglobin \< 8.5 g/dL, WBC count \< 1,000/mm3 , absolute neutrophil count \< 1,000/ mm3, absolute lymphocyte count \< 500/mm3, positive HBsAg or HCV antibody, or positive HIV test. 11. Pregnant women or nursing mothers 12. Females of child bearing potential who are not using reliable means of contraception 13. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine or GI disease 14. Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel syndrome, where flares are commonly treated with corticosteroids 15. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections such as atypical mycobacterial disease, hepatitis B and C, HIV, herpes zoster, or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening. 16. A history of active TB within the last 3 years even if it was treated. A history of active TB greater than 3 years ago unless there is documentation that the prior anti-TB treatment was appropriate in duration and type. A positive PPD skin test (≥5 mm) or positive QuantiFERON-TB Gold serum test without appropriate prophylaxis (at least 1 month of the planned local guidelines treatment regimen) 17. Any malignancy except for skin cancer (basal cell or squamous cell) diagnosed within the previous 5 years 18. History of alcohol, drug, or chemical abuse 19. Neuropathies or other painful conditions that might interfere with pain evaluation