To find molecular pathways active in ST of RA patients who did not respond to TNFi after 3 months of treatment with their first TNFi. This may aid in clinical decision making (on the group level) and may lead to discovering new drug targets.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Synovial gene transcripts associated with non-response.
Secondary outcome
Blood biomarkers associated with non-response and with molecular and
immunological pathways in synovial tissue.
Background summary
~30% of rheumatoid arthritis (RA) patients do not demonstrate an adequate
clinical response to TNF inhibitors (TNFi). We cannot predict which treatment
will be effective in these patients and we do not know which pathways are still
active in the synovial tissue (ST) of these patients.
Study objective
To find molecular pathways active in ST of RA patients who did not respond to
TNFi after 3 months of treatment with their first TNFi. This may aid in
clinical decision making (on the group level) and may lead to discovering new
drug targets.
Study design
This is a single center observational study. The study is largely
cross-sectional with a study visit 3 months after start of treatment with TNFi
at which ultrasound (US) guided synovial biopsy sampling will be performed. A
baseline study visit before initiation of treatment with TNFi is included in
the design to be able to evaluate change in clinical disease activity upon
treatment with TNFi and to be able to assess associations between immunological
blood parameters at baseline and non-response to TNFi after 3 months. 3-4 Days
after the biopsy visit, patients will have a telephone contact to evaluate
complaints during and after the biopsy procedure.
Study burden and risks
Patients will have two study visits during the study, 3 months apart, at which
they will undergo joint examination, and ultrasound of MCP-joints and of both
wrists and knees.
In addition, at each study visit they will undergo blood sampling (at baseline
94.3ml and after 3 months 84.3 ml. The total amount of blood drawn in the study
is 179ml. Patients may develop a hematoma at the site of venepuncture. To
describe the patient population x-rays of hands and feet and of the biopsied
joint will be performed at 3 months, if not performed in the last 12 months. In
addition, at the 3 month study visit patients will undergo US guided synovial
biopsy sampling of one wrist or knee or MCP-joint. Approximately 25% of
patients will have minor discomfort after the procedure. This is effectively
managed with simple analgesia (NSAIDs/paracetamol) and should dissipate after
24 hrs. Patients can walk after the procedure (applicable to patients
undergoing synovial biopsy in knee joint) and can go home on the same day.
Patients are asked to refrain from over exertion and should ideally be
accompanied home by a friend/relative. Below is a list of most commonly
experienced complications with arthroscopic procedures (approximate incidences
in brackets; ref: synovialbiopsy.com):
i) Joint infection (0.2%)
ii) Deep venous thrombosis (0.2%)
iii) Haemarthrosis (1%)
iv) Neurological damage (0.02%)
v) Wound infection (0.5%)
vi) Thrombophlebitis (0.08%)
We expect the complication rate for US guided procedures to be significantly
better.
Theoretically, patients may experience adverse events of lidocaine
hydrochloride used for local anesthesia (as described in standard medication
information).
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
* Age * 18 years
* Fulfilling 2010 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria for RA (Appendix A).
* DAS28 * 3.2
* At least one clinically active wrist or knee or MCP joint
* Start with aTNFi (all currently approved TNFi are allowed* infliximab (3 mg/kg at week 0, 2, 6 and 14), etanercept, adalimumab, golimumab, certolizumab pegol) within 4 weeks from the baseline study visit.
* Having insufficient response to treatment with * 2 conventional DMARDs.
* Current treatment with either methotrexate (*10 mg/week), sulfasalazine (*2000 mg/day), hydroxychloroquine (*200 mg/day), and/or leflunomide (*10 mg/day).
* Naïve to previous biological treatment regimens, including other TNFi, rituximab, abatacept, tocilizumab (and biosimilar equivalents).
Exclusion criteria
* Treatment with systemic glucocorticoids at a dose above 10 mg/day of prednisone or equivalent within 4 weeks of enrolment.
* Treatment with intra-articular glucocorticoids in a knee or wrist or MCP joint within 3 months of enrolment.
* Any rheumatic disease other than RA (except secondary Sjogren*s syndrome)
Design
Recruitment
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 |
|---|---|
| CCMO | NL56944.041.16 |