Prospective study on the effects of etanercept treatment in patients with rheumatoid arthritis who are naive for TNF-alpha blocking therapy or are non-responders to prior treatment with other anti-TNF-alpha medicatio

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 200

Inclusion Criteria

1) Patients with the diagnosis rheumatoid arthritis according to the American Rheumatism Association (ARA) 1987 criteria and in ACR 1991 functional classes I, II, and III (see appendix)
2) The patient is naive for anti-TNF-alpha therapy or has failed other prior TNF-alpha blockers
3) DAS 28 > or <= 3.2
4) Failure on two previously used DMARDs
5) Age > 18 and < or <= 85 years old
6) 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 < or <= 10 mg/day provided that the dosage has been stable for at least 28 days prior to entry.

Exclusion Criteria

1) Pregnancy
2) Breastfeeding
3) A history of or current 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) Therapy within the previous 60 days with:
* any experimental drug
* alkylating agents, e.g. cyclophosphamide, chlorambucil
* antimetabolites
* monoclonal antibodies (including infliximab and adalimumab)
* growth factors
* other cytokines
6) 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
7) Receipt of any live (attenuated) vaccines within 4 weeks prior to baseline
8) Fever (orally measured > 38 °C), chronic infections or infections requiring anti-
microbial therapy
9) Other active medical conditions such as inflammatory bowel disease, bleeding
diathesis, or severe unstable diabetes mellitus
10) Manifest cardiac failure (stage III or IV according to NYHA classification)
11) Progressive fatal disease/terminal illness
12) a history of lymphoproliferative disease or treatment with total lymphoid
irradiation.
13) A white cell count less than 3.5 x 10^9/l
14) Platelet count less than 100 x 10^9/l
15) Haemoglobin of less than 5.3 mmol/l
16) Body weight of less than 45 kg
17) History of drug or alcohol abuse
18) Any concomitant medical condition which would in the investigator*s opinion compromise the patient*s ability to tolerate, absorb, metabolize or excrete the study medication.
19) Inability to give informed consent
20) 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: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary outcomes are:<br /><br><br /><br>1) factors distinguishing responding patients from non responding patients on<br /><br>etanercept treatment Differences in cytokine profiles or other serological<br /><br>markers, RA activity driven by other mediators than TNF-alpha)<br /><br><br /><br>2)percentage of patients (TNF-alpha blockade naïve versus failures on prior<br /><br>anti-TNF-alpha treatment) respond after 16 weeks of etanercept treatment</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secundary outcomes are:<br /><br><br /><br>1) the clinical efficacy of etanercept after 1 year treatment (Eular response<br /><br>criteria (DAS 28), ACR response, RADAI, SF 36, HAQ, and radiological progession)<br /><br><br /><br>2) genetic markers, e.g. genetic polymorphisms in the TNF-alpha genes, that may<br /><br>predict diagnosis, efficacy and side-effects of treatment in the individual<br /><br>patient<br /><br><br /><br>3) periferal blood (mRNA) micro-array analysis identifying new markers that<br /><br>distinguish responders from non-responders to etanercept treatment</p><br>