Anti-TNF Agents for the Treatment of Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Etanercept; Adalimumab
Intervention description: 50 mg dose of etanercept by subcutaneous injection; 40 mg dose of adalimumab by subcutaneous injection
Intervention MeSH terms: Adalimumab; Etanercept
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: tumor necrosis factor (TNF) blockade; inflammatory autoimmune disorder

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of RA*

          -  Disease duration as defined from the onset of symptoms of at least 3 months prior to
             study entry

          -  Active RA with DAS28 > 4.4, clinically requiring the addition of anti-TNF therapy

          -  Stable dose of MTX between 7.5 mg and 25 mg weekly for at least 8 weeks prior to study
             entry

          -  Able and willing to self-administer subcutaneous injections or have available
             qualified person(s) or caregiver to administer subcutaneous injections

          -  For females, agree to use accepted methods of contraception during the duration of the
             study and for 150 days after study completion*. *More information on these criterion
             can be found in the protocol.

        Exclusion Criteria:

          -  Positive PPD test - a tuberculosis (TB) skin test: (> 5 mm induration regardless of
             prior Bacille Calmette-Guerin [BCG] vaccine administration) without evidence of
             ongoing treatment for at least 30 days or completed treatment

          -  History of positive PPD or chest x-ray findings indicative of prior TB infection,
             without documentation of either treatment for TB infection or chemoprophylaxis for TB
             exposure

          -  Prednisone dose > 10 mg/day (or equivalent dose of another corticosteroid) within 30
             days prior to study entry

          -  Definitive diagnosis of another autoimmune disease that may require immunosuppression
             for treatment*

          -  Concomitant use of DMARDSs (e.g., disease-modifying antirheumatic drugs)*

          -  Any immunosuppressive therapy other than MTX, NSAIDs, or corticosteroids*

          -  Current or previous use of any biologic agent

          -  Presence of open leg ulcers

          -  Chronic or persistent infection that might be worsened by immunosuppressive treatment*

          -  Active infection or severe infections requiring hospitalization or treatment with
             intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to
             study entry

          -  Received oral antibiotics, antivirals, or antifungals within 14 days prior to study
             entry

          -  Certain abnormal laboratory values*

          -  Any medical condition that, in the opinion of the investigator, would interfere with
             the study

          -  History of malignancy other than treated localized carcinoma in situ of the cervix or
             adequately treated non-metastatic squamous or basal cell skin carcinoma within 10
             years prior to study entry

          -  Any Investigational agent within the earlier of 4 weeks or 5 half-lives prior to study
             entry

          -  History of drug or alcohol abuse within 6 months prior to study entry

          -  Known allergy or hypersensitivity to study products

          -  Inability or unwillingness to follow the protocol

          -  Any condition or treatment that, in the opinion of the investigator, places the
             participant at an unacceptable risk

          -  Pregnant or breastfeeding *More information on these criterion are in the protocol.