Biomarkers of Anti-TNF-α Therapy Efficacy in Rheumatoid Arthritis to Define Unresponsive Patients

Patients with rheumatoid arthritis (RA) are generally treated with Tumor Necrosis
Factor-alpha (TNF) inhibitors as second-line therapy if an oral medication such as
methotrexate (MTX) is not adequate to control the symptoms. If one anti-TNF therapy does
not lead to adequate symptom control, the current standard of care dictates switching to
another approved anti-TNF agent, even though response rates deteriorate with each cycle.
Pilot research at Biogen Idec and academic collaborators has developed a panel of gene
expression markers with approximately 90% positive and negative predictive values to
identify individuals who did not achieve European League Against Rheumatism (EULAR) Disease
Activity Score (DAS)-28 Good response after 14 weeks of treatment. Such a biomarker panel
could be used as a diagnostic test to direct therapeutic options.

Inclusion Criteria

To be eligible to participate in this study, candidates must meet the following
eligibility criteria at the time of enrollment:

1. Are willing and able to provide informed consent.

2. Are 18 years of age or older.

3. Meet the ACR criteria for RA as determined by a rheumatologist who is board certified
in Rheumatology or a member of the ACR.

4. Have 4 or more tender and 4 or more swollen joints out of 28 joints as assessed by
their treating rheumatologist or a trained joint assessor.

5. Subjects are not taking any of the following treatments and/or have washed out for
the minimum duration as defined below. If subjects are currently taking these
treatments, must have been on a stable dosing regimen for the minimum duration as
defined below:

- Oral DMARDs (MTX, hydroxychloroquine, sulfasalazine, leflunomide, cyclosporine,
azathioprine): on drug for at least 3 months and washed out or stable for at
least 6 weeks prior to baseline sample collection.

- Oral corticosteroids: washed out or stable AND ≤10 mg/day of prednisone
equivalent for at least 4 weeks prior to baseline sample collection.

- Intraarticular or parenteral corticosteroids: Washed out or stable for at least
4 weeks prior to baseline sample collection.

- NSAIDs: Washed out or stable for at least 2 weeks prior to baseline sample
collection.

6. Are about to start treatment with an anti-TNF agent approved for the treatment of RA
for the first time OR Have not, in the opinion of the treating rheumatologist,
achieved or maintained an adequate response to treatment with their first anti-TNF
agent (any anti-TNF agent approved for the treatment of RA), and have been prescribed
a different anti TNF agent. Subjects who switch for any reason other than lack of
efficacy will be excluded.

Exclusion Criteria

Candidates will be excluded from study entry if any of the following exclusion criteria
exist at the time of enrollment:

1. Any medical condition that would preclude safe use of an anti-TNF agent for at least
14 weeks.

2. Previous participation in the present study as a subject in the anti-TNF-naïve group.

3. Prior exposure to 2 or more anti-TNF agents.

4. Prior exposure to Orencia (abatacept, or CTLA4-Ig) and/or Rituxan (anti CD20), or
other biologic therapy for RA or other diseases.