Inclusion Criteria:
1. Males and females >= 18 years of age.
2. A negative pregnancy test (human chorionic gonadotropin in serum samples) for women of
childbearing potential prior to start of study treatment.
3. Female subject is either not of childbearing potential, defined as postmenopausal (at
least 1 year since last menses) or surgically sterile (bilateral tubal ligation,
bilateral oophorectomy or hysterectomy), or is of childbearing potential and
practicing one of the following methods of birth control throughout the study and for
150 days after study completion:
- Condoms, sponge, foams, jellies, diaphragm or intrauterine device.
- Contraceptives (oral, parenteral, patch) for three months prior to study drug
administration.
- A vasectomized partner.
4. American College of Rheumatology criteria for diagnosis of rheumatoid arthritis for at
least 6 months.
5. Subjects must meet the following three criteria:
- Disease Activity Score (28 joints) more or equal 3.2 (at Baseline only)
- At least 6 swollen joints out of the 66 assessed
- At least 8 tender joints out of the 68 assessed
6. Subjects must have a C-reactive protein >= 1.5mg/dL or erythrocyte sedimentation rate
>= 28 mm/1h.
7. Unsatisfactory response or intolerance to prior disease modifying anti-rheumatic drugs
(must have failed at least 1 disease modifying anti-rheumatic drug).
8. Able and willing to administer subcutaneous injections.
9. Able and willing to give written informed consent and to comply with the requirements
of the study protocol.
10. Documented negative purified protein derivative test, defined as < 5 mm induration, or
willingness and ability to start tuberculosis prophylaxis before first dose of study
drug if the purified protein derivative result is positive and the chest X-ray is not
suggestive of active tuberculosis and there is no history of active tuberculosis.
Exclusion Criteria:
1. Prior treatment with alkylating agents such as cyclophosphamide or chlorambucil within
at least 5 years before enrollment.
2. Prior treatment with intravenous immunoglobulin or any investigational agent
"chemical" in nature within 30 days, or 5 half lives of the product, whichever is
longer.
3. Prior treatment with cyclosporine within the last 6 months.
4. Prior treatment with investigational biologic therapy.
5. Subject has chronic arthritis diagnosis before the age 17 years.
6. Subject has undergone joint surgery within the preceding two months (at joints to be
assessed within the study).
7. History of an allergic reaction or significant sensitivity to the constituents of
study drug (adalimumab).
8. Treatment within the last 2 months with approved biologic therapy (e.g. infliximab)
prior to Baseline.
9. Prior treatment with total lymphoid irradiation.
10. History of cancer or lymphoproliferative disease other than a successfully and
completely treated non-metastatic cutaneous squamous cell or basal cell carcinoma
and/or localized carcinoma in situ of the cervix.
11. History of or current acute inflammatory joint disease of origin other than rheumatoid
arthritis, e.g. mixed connective tissue disease, systemic lupus erythematosus etc.
12. History of uncontrolled diabetes, unstable ischemic heart disease, congestive heart
failure (New York Heart Association III-IV), active peptic ulcer disease, recent
stroke (within 3 months) and any other condition which, in the opinion of the
investigator, would put the subject at risk by participation in the protocol.
13. Subject is known to have immune deficiency, history of positive human immunodeficiency
virus status or is immunocompromised.
14. Persistent chronic infection, or severe infections requiring hospitalization or
treatment with intravenous antibiotics within 30 days, or oral antibiotics within 14
days prior to enrollment.
15. Female subjects who are pregnant or breast-feeding or is considering becoming pregnant
during the study or for 150 days after the last dose of study medication.
16. History of clinically significant drug or alcohol abuse in the last year.
17. Previous diagnosis or signs of central nervous system demyelinating diseases.
18. History of untreated or active tuberculosis, histoplasmosis or listeriosis.
19. History of clinically significant hematologic (e.g. severe anemia, leucopenia,
thrombocytopenia), renal or liver disease (e.g. fibrosis, cirrhosis, hepatitis).
20. Screening clinical laboratory analysis showing any of the following abnormal
laboratory results:
- Aspartate transaminase or alanine transaminase > 1.75 x the upper limit of
normal.
- Serum total bilirubin >= 1.5 mg/dL (>= 26 micromol/L).
- Creatinine > 1.5 mg/dL (133 micromol/L) in subjects < 65 years old and > upper
limit of normal range in subjects >= 65 years old.
- Positive Hepatitis B or C serology indicative of previous or current infections.
21. Subject is considered by the Investigator, for any reason, to be an unsuitable
candidate for the study.
