Anti-TNF Agents for the Treatment of Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 4

Summary: 
      Rheumatoid arthritis (RA) is a chronic disease that leads to inflammation and progressive
      joint damage. RA is a systemic inflammatory autoimmune disorder affecting almost 1% of the
      United States population. Current therapies target the immune system early in the disease
      process before joint damage occurs, and include drugs such as methotrexate (MTX) and tumor
      necrosis factor (TNF)-blocking agents. The primary purpose of this study is to determine the
      effectiveness of two TNF inhibitors, etanercept and adalimumab, on memory B lymphocytes
      (B-cells) in the peripheral blood of participants with RA.

      Additionally, there are 4 optional sub-studies as part of the trial:

        -  B-Cell Kinetic Sub-Study to look at changes in B-cell subsets over time and how quickly
           reductions in B-cell memory occur

        -  Vaccine Response Sub-Study to assess B cell memory in response to immunization with
           hepatitis B,-hepatitis A, and diphtheria/tetanus vaccines, and to determine whether
           T-cell vaccine responses are altered with TNF blockade

        -  Tonsil Biopsy Sub-Study to evaluate how TNF blockade affects memory B-cells in the
           tonsil dendritic cells and germinal cells

        -  Synovial Biopsy Sub-Study to evaluate how TNF blockade affects changes in memory B-cells
           in lymphoid tissue.
    

Detailed description: 
      RA is characterized by persistent inflammation of peripheral joints, causing pain, stiffness,
      swelling and warmth. Over the past 10 years, advancements in biotechnology have
      revolutionized RA therapeutics with biologically-derived immunomodulating compounds.
      TNF-alpha inhibitors constitute the largest class of these new biologic therapies. The
      purpose of this study is to determine the effectiveness two TNF inhibitors, etanercept and
      adalimumab, on memory B lymphocytes (B-cells) in the peripheral blood of participants with
      RA.

      This study will last 24 weeks. Participants will be randomized into one of two treatment
      groups. Participants in one group will receive a dose of etanercept once every week for 24
      weeks. Participants in the other group will receive a dose of adalimumab once every 2 weeks
      for 24 weeks.

      This study consists of seven study visits after randomization and will occur at study entry
      and Weeks 4, 8, 12, 16, 20 and 24. Blood collection will occur at all study visits. A written
      participant assessment, vital signs, and physical exam will occur at study entry and Weeks 12
      and 24. Follow-up calls to assess safety are scheduled for Weeks 4, 8, 16, and 20.

      Additionally, participants will be offered the opportunity to enter one of four sub-studies
      as mentioned in the brief summary above: B Cell Kinetic Sub-Study, Vaccine Response
      Sub-Study, Tonsil Biopsy Sub-Study, and Synovial Biopsy Sub-Study. More information on these
      sub-studies is in the protocol.
    

Intervention name(s): Etanercept; Adalimumab
Intervention type(s): Drug; Drug
Intervention description(s): 50 mg dose of etanercept by subcutaneous injection; 40 mg dose of adalimumab by subcutaneous injection
Other intervention name(s): Enbrel®; Humira®)
Intervention MeSH terms: Adalimumab; Etanercept
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: tumor necrosis factor (TNF) blockade; inflammatory autoimmune disorder