A Study of Adalimumab When Added to Inadequate Standard Anti-rheumatic Therapy in Patients With Active Rheumatoid Arthritis

An Open-label, Prospective, Multi-Centre Study to Assess the Safety and Efficacy of Adalimumab (Humira®) When Added to Inadequate Standard Anti-Rheumatic Therapy in Patients With Active Rheumatoid Arthritis

A total of 100 participants diagnosed with active rheumatoid arthritis were enrolled at 5 sites in Russia. Adalimumab was administered by subcutaneous injection every other week, with dose escalation to weekly dosing available for participants not receiving concomitant disease-modifying antirheumatic drugs (DMARDs) who did not achieve American College of Rheumatology 20 (ACR20) criteria after 12 weeks of treatment. Efficacy and safety measurements were performed throughout the study.

This is an open-label, multicenter study designed to establish the safety and efficacy of adalimumab in the treatment of moderate to severely active rheumatoid arthritis. A total of 100 subjects with inadequate preexisting standard anti-rheumatic therapy were enrolled at 5 sites in Russia.

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.