To evaluate the response to etanercept treatment in TNF-alpha blockade naïve patients and patients who failed prior other anti-TNF-alpha treatment and to understand the mechanisms underlying the clinical response to TNF-alpha blockade
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcomes are:
1) factors distinguishing responding patients from non responding patients on
etanercept treatment Differences in cytokine profiles or other serological
markers, RA activity driven by other mediators than TNF-alpha)
2)percentage of patients (TNF-alpha blockade naïve versus failures on prior
anti-TNF-alpha treatment) respond after 16 weeks of etanercept treatment
Secondary outcome
The secundary outcomes are:
1) the clinical efficacy of etanercept after 1 year treatment (Eular response
criteria (DAS 28), ACR response, RADAI, SF 36, HAQ, and radiological progession)
2) genetic markers, e.g. genetic polymorphisms in the TNF-alpha genes, that may
predict diagnosis, efficacy and side-effects of treatment in the individual
patient
3) periferal blood (mRNA) micro-array analysis identifying new markers that
distinguish responders from non-responders to etanercept treatment
Background summary
Previous randomised trials have shown the efficacy of etanercept in RA
patients. In this study we will evaluate the respons of etanercept in anti-TNF
naive patients compared to patients who have failed other anti-TNF. We will
look for clinical parameters and serological markers that may differentiate
responders from non-responders on etanercept.
Study objective
To evaluate the response to etanercept treatment in TNF-alpha blockade naïve
patients and patients who failed prior other anti-TNF-alpha treatment and to
understand the mechanisms underlying the clinical response to TNF-alpha
blockade
Study design
A monocenter prospective, exploratory study with a 2 to 4-week screening period
and a 52-week follow-up period
Study burden and risks
Patients will visits our outpatient clinic seven times during this study. They
will get a physical exam and blood test each time they come. During visits 2
till 7 they have to fill out a questionnary (ACR Radai, HAQ, VAS, morning
stiffness, SF36) and give urine for tests. The objects will get a X-chest at
the screening and during this study there will be two X-hands and X-foots made.
Meibergdreef 9 F4-105
1105 AZ Amsterdam ZO
NL
Meibergdreef 9 F4-105
1105 AZ Amsterdam ZO
NL
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-015653-20-NL |
| CCMO | NL29616.018.09 |
| Other | Not applicable |