Identification of predictive factors in synovial samples for the clinical response to tumour necrosis factor-alpha blockade in rheumatoid arthritis

Completed

• Conditions: Rheumatoid arthritis; Musculoskeletal Diseases; Arthropathies

• Registration Number: ISRCTN36847425
• Lead Sponsor: Academic Medical Centre (AMC) (The Netherlands)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02-01
• Last Update Posted: 13 January 2015

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 143

Inclusion Criteria

1. Men/women suffering from rheumatoid arthritis, based on the American Rheumatism Association (ARA) 1987 criteria, who failed at least one Disease Modifying Anti-Rheumatic Drug (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. Disease Activity Score (DAS 28) more than 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. more than 18 years of age and less than or equal to 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 of less than or equal to 10 mg/day provided that the dosage has been stable for at least two months prior to entry

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 fusion protein
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 intra-articular 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 as more than 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 New York Heart Association [NYHA] classification)
13. Progressive fatal disease/terminal illness
14. Impaired coagulation
15. A congenital or acquired (known Human Immunodeficiency Virus [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), or a haematopoietic disease
16. A white cell count less than 3.5 x 10^9/l
17. Platelet count less than 100 x 10^9/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, metabolise 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Primary immunohistological outcome: TNF-alpha expression in synovial tissue as shown by immunohistochemistry and quantified by digital image analysis<br>2. Primary clinical outcome: clinical response at week 16 assessed using the DAS 28

Secondary Outcome Measures

Name	Time	Method
Secondary immunohistological outcome: analysis of the synovial cell infiltrate, and cytokines other than TNFalpha.