Anti-TNF Agents for the Treatment of Rheumatoid Arthritis

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.

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.