Identification of predictive factors in synovial samples for the clinical response to TNF-alpha blockade in rheumatoid arthritis.

1. Men/women suffering from rheumatoid arthritis, based on the American Rheumatism Association (ARA) 1987 criteria, who failed at least one DMARD including methotrexate will be included in the study;

2. Patients in ARA functional classes I, II, and III may be included;

3. In addition the patients must fulfill the following criteria at baseline:

a. DAS 28 >3.2;

b. Patients global evaluation of his/her rheumatoid condition assessed as fair, poor or very poor;

and

investigators global evaluation of patients rheumatoid condition assessed as fair, poor or very poor;

c. Be > 18 years of age and <= 85 years;

d. Use concurrent methotrexate treatment (5 - 30 mg/week; stable since at least 28 days before initiation) during the study. Subjects may be taking nonsteroidal anti-inflammatory drugs, provided the dose and frequency have been stable for at least 28 days. Subjects may be receiving prednisone therapy <=10 mg/day provided that the dosage has been stable for at least 2 months prior to entry.

1. Pregnancy;

2. Breastfeeding;

3. A history of or acute inflammatory joint disease of different origin e.g. mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter¡¦s syndrome, systemic lupus erythematosus or any arthritis with onset prior to age 16 years;

4. Acute major trauma;

5. Previous therapy at any time with: TNF-alpha directed monoclonal antibodies or p75 TNF receptor fusionprotein;

6. Therapy within the previous 60 days with:

a. Any experimental drug;

b. Alkylating agents, e.g. cyclophosphamide, chlorambucil;

c. Antimetabolites;

d. Monoclonal antibodies;

e. Growth factors;

f. Other cytokines;

7. Therapy within the previous 28 days with:

a. Parenteral or intraarticular corticoid injections;

b. Oral corticosteroid therapy exceeding a prednisone equivalent of 10 mg daily;

c. Present use of DMARDs other than methotrexate;

8. A history of hypersensitivity to the study medication or to drugs with similar chemical structure;

9. Fever (orally measured > 38 °C), chronic infections or infections requiring anti-microbial therapy;

10. Known positive reaction to hepatitis B surface antigen;

11. Other active medical conditions such as inflammatory bowel disease, bleeding diathesis, or severe unstable diabetes mellitus;

12. Manifest cardiac failure (stage III or IV according to NYHA classification);

13. Progressive fatal disease/terminal illness;

14. Impaired coagulation;

15. A congenital or acquired (known HIV-positive status) immunodeficiency, a history of cancer or lymphoproliferative disease or treatment with total lymphoid irradiation.

(The known HIV-positive status may be defined either by a positive blood test or clinical diagnosis.)
a haematopoietic disease;

16. A white cell count less than 3.5 x 109/l;

17. Platelet count less than 100 x 109/l;

18. Haemoglobin of less than 5.3 mmol/l;

19. Body weight of less than 45 kg;

20. History of drug or alcohol abuse;

21. Any concomitant medical condition which would in the investigators opinion compromise the patients ability to tolerate, absorb, metabolize or excrete the study medication;

22. Inability to give informed consent;

23. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.