A Rheumatoid Arthritis Study to Assess Early Response to Abatacept+MTX as Defined by Improvement of Synovitis Measures by Power Doppler Ultrasonography
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Abatacept; Methotrexate
Intervention description: Abatacept, 10 mg/kg, solution given intravenously on Days 1, 15, 29,57, 85, 113, 141, and 169; Methotrexate administered in a dose of 15 mg/week or higher for at least 3 months and at a stable dose for at least 28 days prior to baseline
Intervention MeSH terms: Methotrexate; Abatacept
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to assess early signs of response to abatacept+methotrexate in
      metacarpophalangeal joints in both hands using power Doppler ultrasonography in patients with
      active rheumatoid arthritis.
    

Eligibility criteria:

        Key inclusion riteria:

          -  Disease activity defined by a disease activity score 28-C-reactive protein >3.2, or
             meeting the following criteria: a tender joint count ≥6; a swollen joint count ≥6;
             C-reactive protein measurement greater than the upper limit of normal

          -  Diagnosis of rheumatoid arthritis for longer than 6 months from time of initial
             diagnosis

          -  Total synovitis power Doppler ultrasonography (PDUS) score >1 for at least 2
             metacarpophalangeal (MCP) joints (MCP2-5) and a total synovitis PDUS score ≥1 for at
             least 1 other MCP joint (MCP2-5)

          -  Concomitant treatment with methotrexate at a dose ≥15 mg for at least 3 months before
             Day 1 and a stable dose for the last 28 days before Day 1

          -  No treatment with any background nonbiologic disease-modifying antirheumatic drug
             (DMARD) other than methotrexate for at least 28 days before treatment (Day 1)

          -  Stable dose of corticosteroids equivalent of 10 mg prednisone /day during the 28 days
             prior to Day 1

          -  Naive to treatment with biologic DMARDs

        Key exclusion criteria:

          -  Women of childbearing potential who are unwilling or unable to use birth control

          -  Women who are pregnant or breastfeeding

          -  Meeting all diagnostic criteria for any other rheumatic disease

          -  Previous MCP arthroplasty, with such a procedure scheduled, or anticipating the need
             for such a procedure during the study. Participants who had undergone or were
             scheduled to undergo joint arthroplasties other than of the MCP joints were permitted
             to enroll in the study provided all other eligibility criteria were met.

          -  Active vasculitis of a major organ system with the exception of rheumatoid nodule

          -  Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic,
             gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not
             related to rheumatoid arthritis

          -  History of cancer in the last 5 years, other than nonmelanoma skin cell cancer cured
             by local resection or carcinoma in situ. Existing nonmelanoma skin cell cancers should
             have been removed, the lesion site healed, and residual cancer ruled out prior to
             administration of study medication

          -  Clinically significant abuse of alcohol or drugs

          -  Evidence of active or latent bacterial or viral infections at the time of potential
             enrollment

          -  Herpes zoster or cytomegalovirus infection that resolved less than 2 months before the
             informed consent document was signed

          -  For participants at risk for tuberculosis (TB):

               -  A history of active (TB) within the last 3 years, even if treated

               -  Latent TB that was not successfully treated ≥4 weeks

               -  Current clinical, radiographic, or laboratory evidence of active TB.

          -  Participants who have received live vaccines within 3 months of the anticipated first
             dose of study medication

          -  Participants with positive test results for hepatitis B surface antigen or hepatitis C
             antibody, with hepatitis C virus detected with polymerase chain reaction or
             recombinant immunoblot assay.

          -  Participants with hemoglobin level <8.5 g/dL or white blood cell count< 3000/mm^3 or
             platelet count <100,000/mm^3 or serum creatinin level >2*the upper limit of normal
             (ULN) or serum alanine transaminase level or aspartate aminotransferase level >2*ULN