It is our goal to predict the efficacy of glucocorticoid-treatment of RA patients by means of a list of markers predicting the reponse to GC treatment in order to avoid ineffective but potentially harmful treatment in the glucocorticoid non-…
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Autoimmune disorders
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
A list of markers seen in monocytes and T cells that are differently expressed
in GC-responders versus GC nonresponders.
Secondary outcome
A list of markers seen in monocytes and T cells that are differently expressed
in patients experiencing side effects and patients without side effects.
Background summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by
inflammation of joints leading to joint destruction. Thus far no curative
therapy is available, the therapeutic possibilties range from conventional
disease modifying anti-rheumatic drugs to the more recent expensive biological
agents and also include very often glucocorticoids (GC). Glucocorticoids are a
costefficient medication which have been proven to be effective in suppression
of inflammation as well as in retardation of joint destruction, but often cause
undesirable side effects. However, 25-30% of patients do not respond to
glucocorticoid therapy at all or only to a minimal extent, and some patients
might thus be subject to unnecessary side effects. It is therefore of major
importance to distinguish patients who respond to GC therapy from patients who
benefit to a lesser extent or even not at all from this treatment in order to
save the latter from unnecessary damaging side effects.
Study objective
It is our goal to predict the efficacy of glucocorticoid-treatment of RA
patients by means of a list of markers predicting the reponse to GC treatment
in order to avoid ineffective but potentially harmful treatment in the
glucocorticoid non-responsive individuals.
Study design
In order to find a limited list of markers predicting the efficacy of GC
treatment, a multitude of candidate proteins need to be tested in a big cohort
simultaneously, which is not feasable in practice. Thus we intend to make use
of gene expression profiling, which makes it possible to evaluate a great
number of expressed genes simultaneously, thus avoiding the cost- and
time-consuming analysis of single factors.
Patients with active RA that are being treated with GC according to daily
practice in our department are categorized into GC-responders and
GC-nonresponders according to the EULAR response criteria using the DAS28
score. There are two different treatment regimes used, one high dose
intravenous and a low dose oral regime, which are both examined in this study.
After establishing their GC - responderstatus, 10 GC- nonresponders and 10 GC
responders (of both treatment regimens, thus ca. 80 patients: 2x 40) will be
examined concerning their gene expression profile before and after the first
dose of GC. The difference in gene expression between responders and
nonresponders will be computed by analysis programmes as SAM and treeview,
based on the respective expression level of the transcribed genes on the cDNA
chips of the patients. This analysis will thus yield a long list of
differentially expressed genes between GC responders and GC-nonresponders. An
evaluation of this list concerning the magnitude of the difference of
expression (eg difference of normalized expression value or in statistical
significance) or the feasibility of future tests (eg: is there an antibody
avalaible against the protein encoded by the upregulated mRNA?) is made by the
researcher. Subsequently, based on this evaluation a verification of selcted
markers will be carried out by protein assays and/or RT-PCR. in this manner, a
short list of selected and verified markers can be obtained for a future
validation step in a different study.
Altogether this study shall contribute to the emergence of a more customized
treatment for RA patients, preventing unnecessary and often debilitating side
effects in patients, who do not benefit of a glucocorticoid treatment.
Study burden and risks
Patients do not undergo any additional risk or burden, as they are treated
according to daily practice in our department and no additional intervention is
carried out.
Heidelberglaan 100
3584CX Utrecht
NL
Heidelberglaan 100
3584CX Utrecht
NL
Listed location countries
Age
Inclusion criteria
Clinical indication for Glucocorticoid therapy either in high dose (Cohort A) or low dose (Cohort B) based on the judgement of the treating/attending physician according to clinical practice in our outpatient clinic.
Exclusion criteria
1) Clinical contrandications for GC-therapy as handled in our outpatient clinic
2) Change of (DMARD) medication in the last month
3) GC treatment in the last month in both cohorts.
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 | NL24429.041.08 |