Rheumatoid arthritis.
Conditions
Interventions
Infliximab therapy (3mg/kg i.v.) at week 0, 2, 6, 14 and every 8 weeks. Clinical efficacy assessments are performed at baseline and subsequently every 4 weeks up to week 24. Serum samples are drawn on
Sponsors
AMC, Division of Clinical Immunology and Rheumatology.
Eligibility
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Primary immunohistologic outcome: TNF-alpha expression in synovial tissue as shown by immunohistochemistry and quantified by digital image analysis; 2. Primairy clinical outcome: Clinical response at week 16 assessed using the DAS28. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary immunohistologic outcome: Analysis of the synovial cell infiltrate, and cytokines other than TNFalpha. | — |
Contacts
Public ContactC.A. Wijbrandts
Academic Medical Center (AMC), Department of Medicine, Division of Clinical Immunology and Rheumatology, F4-218, P.O. Box 22660
Outcome results
None listed