CSP #551 - Rheumatoid Arthritis: Comparison of Active Therapies in Patients With Active Disease Despite Methotrexate Therapy

Inclusion Criteria:

1. All patients must fulfill ACR classification criteria for rheumatoid arthritis.

2. All patients must have been 16 years of age or older at time of diagnosis of
rheumatoid arthritis.

3. All patients must be 18 years of age or older at the time of entry into the study.

4. All patients will have been receiving oral or subcutaneous methotrexate 15 to 25
mg/week (unless intolerant and on a minimum 10 mg/week) at a constant dose for at
least 4 weeks, and on any methotrexate for no less than 12 weeks.

5. All patients will have active disease as defined by a DAS28 of greater than or equal
to 4.4.

6. If patients are receiving corticosteroids, they must have been on stable dose (less
than or equal to 10 mg prednisone or equivalent) for at least two weeks prior to
screening.

7. If patients are using non-steroidal anti-inflammatory drugs (NSAIDs), they must be on
stable doses for at least one week prior to screening.

8. If patients have taken leflunomide, cyclosporine, gold, Anakinra, azathioprine, or
penicillamine in combination with methotrexate, they must have stopped this therapy
at least 8 weeks prior to randomization.

9. Laboratory tests must meet the following criteria within 2 weeks of randomization:

1. Serum creatinine 1.8 mg/dL

2. Hemoglobin 9 g/dL

3. WBC 3000 mc/L

4. Neutrophils 1000 mc/L

5. Platelets 100,000 mc/L

6. Serum transaminase level (AST or ALT, whichever is followed at the site) not
exceeding 1.2 times upper limit of normal.

7. Albumin no less than 1.0 g/dL (10 g/L) below lower limit of normal. Anything
below lower limit of normal must have been stable (or improving) for no less
than 90 days. Stable is defined as changes of no more than 0.2 g/dL (2 g/L).

10. All patients must be capable of giving informed consent and able to adhere to study
visit schedule.

11. Subject or designee must have the ability to self-inject investigational product or
have a caregiver who can inject subcutaneous injections

12. Subjects must meet one of the following criteria with regard to tuberculosis. PPD
must be within 180 days of randomization if the patient has no recent exposure/travel
history, or within 90 days if the patient has a recent exposure/travel history.

1. Negative PPD; or

2. Positive PPD <5 mm, with a negative chest x-ray; or

3. Positive PPD >5mm, treated for at least 28 days with INH.

13. Subjects with an Erythrocyte sedimentation rate (ESR) of less than or equal to 10 and
a tender and swollen joint count of at least 10 and does not qualify for the study
using the DAS28, will be allowed to use the DAS28-CRP rather than the traditional
DAS28 to determine eligibility.

Exclusion Criteria:

1. Previous intolerance to methotrexate (unless able to tolerate at least 10 mg/week)

2. Sensitivity to study medications

3. Previous treatment with methotrexate, sulfasalazine or hydroxychloroquine in
combination with each other for longer than 4 weeks duration. No combination use is
allowed within 4 weeks of screening.

4. No bed or wheelchair-bound patients

5. Previous treatment with a TNF- inhibitor (etanercept, infliximab or adalimumab) for
more than 5 weeks of therapy. Previous treatment with TNF- inhibitor must have been
stopped for reasons other than toxicity or efficacy. No TNF- inhibitor therapy is
allowed within the following time frames:

1. Last dose of etanercept must have been at least 4 weeks before screening.

2. Last dose of adalimumab or infliximab must have been at least 8 weeks prior to
screening.

Example of an eligible patient: A patient found he could not afford the co-pays for
a TNF inhibitor after two doses and stopped taking the medication two months before
being evaluated for this trial.

6. Evidence of important acute or chronic infections (no IV antibiotics within 1 month,
and no PO antibiotics within 2 weeks)

7. Pregnant or nursing women

8. Women of childbearing potential or their partners who are not practicing an
acceptable form of birth control as de