Effects of adalimumab on biomarkers in synovial tissue in patients with rheumatoid arthritis

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

Disease Activity Score (DAS) 28 ><= 3.2
Be > 18 years of age and <85 years.
Use concurrent methotrexate treatment (5 - 30 mg/week; stable for at least 28 days before study enrolment) 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 1 month prior to entry.

Exclusion Criteria

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
Acute major trauma
5)Therapy within the previous 60 days with:
* any experimental drug
* alkylating agents, e.g. cyclophosphamide, chlorambucil
* antimetabolites
* monoclonal antibodies
* growth factors
* other cytokines
Therapy within the previous 28 days with:
* parenteral or intraarticular corticoid injections
* oral corticosteroid therapy exceeding a prednisone equivalent of 10 mg daily
* present use of DMARDs other than methotrexate
Fever (orally measured > 38°C), chronic infections or infections requiring anti-microbial therapy
Other active medical conditions such as inflammatory bowel disease, bleeding diathesis, or severe unstable diabetes mellitus
Manifest cardiac failure (stage III or IV according to NYHA classification)
Impaired coagulation
A congenital or acquired 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.)
Platelet count less than 100 x 109/l
Inability to give informed consent
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
<p>Analysis of the changes in the cellular infiltrate and the expression of<br /><br>cytokines will be performed by immunohistochemical staining, analyzed by<br /><br>digital image analysis<br /><br><br /><br>The following biomarkers will be assessed:<br /><br>* CD3 (T-cell marker)<br /><br>* CD4<br /><br>* CD8<br /><br>* CD22 (B-cell marker)<br /><br>* CD68 (macrophages)<br /><br>* CD163 (resident tissue macrophages)<br /><br>* MRP8 (S100A8, infiltrating macrophages)<br /><br>* MRP14 (S100A9, infiltrating macrophages)<br /><br>* CD38 (plasma cells)<br /><br>* CD55 (fibroblast like synoviocytes)<br /><br>* CD15 (neutrophils)<br /><br>* IL-1<br /><br>* IL-6<br /><br>* TNFalpha<br /><br>* Tweak/ Fn14</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The endpoint of clinical efficacy will be evaluated at week 8 and week 16 after<br /><br>start of adalimumab therapy. Clinical response will analysed by the change in<br /><br>DAS28 score and according to the EULAR response criteria.<br /><br><br /><br>Immunohistochemistry and PCR analysis of the following cytokines in the<br /><br>peripheral blood and synovial tissue will be performed<br /><br><br /><br>Tissue samples and peripheral blood will be stored for future microarray and<br /><br>PCR-analysis.<br /><br><br /><br>Cellular reactions of the synovial cells measured by cytokine production in<br /><br>fresh synovial biopsies before and after treatment will be assessed. </p><br>