Rheumatoid Arthritis Clinical Trial
Official title:
A Study on the Prevalence of the Modified Citrullinated Vimentin Anti-body (Anti-MCV) in an Irish Rheumatoid Arthritis (RA) Population and to Assess the Impact of Anti-MCV and the Anti-cyclic-citrullinated Peptide Antibody (Anti-CCP) Status on the Management of Irish Patients With Early RA
A key challenge in the management of patients with Rheumatoid Arthritis (RA) is the early
identification of patients that are at risk of developing a severe and destructive disease.
A better understanding of prognostic factors such as anti-CCP and anti-MCV biomarkers, is
needed in order to better identify patients with early Rheumatoid Arthritis that are at risk
of developing aggressive diseases. At the present time the prevalence of one such biomarker,
namely anti-MCV, is unknown in an Irish Rheumatoid Arthritis population. This study will
establish the prevalence of anti-MCV in such a population.
A second challenge in the management of Rheumatoid Arthritis patients is the determination
of the best treatment strategy tailored to individual patient's needs. In routine practice,
treatment approaches are based on the patient history and the availability of clinical
parameters, such as a positive anti-CCP status, which is associated with worst prognostics.
At the present time, the impact of a positive anti-CCP status on patients' management has
not been formally studied in Ireland The proposed study will provide data on the prevalence
of anti-MCV in an Irish RA population and the use of anti-CCP and other clinical parameters
currently used in routine care. In addition, the present study will evaluate the impact of
the known anti-CCP status on patients' management. Associations between the anti-CCP and
anti-MCV status and clinical outcome measures will be assessed.
The results from the present study will have significant implications not only for the
individual patient but also from the societal perspective, since it will enhance the overall
understanding and applications of different treatment approaches based on individual
patients' profile.
Results from clinical studies suggest that approximately 73% of patients with Rheumatoid
Arthritis present evidences of erosions within 2 years of the diagnosis. Early interventions
with Disease Modifying Anti-Rheumatic Drug (DMARD) therapies have been shown to reduce the
progression of the disease. Significant differences in mean Sharp scores were observed two
years after the initiation of such treatment regimens. These data support the existence of a
"therapeutic window", during which the rheumatoid process should be stopped or retarded in
order to prevent further articular damages. Importantly, these observations constituted the
premise of subsequent researches aiming at evaluating the benefits of TNF inhibitors in
patients with early and aggressive rheumatoid arthritis.
The detection of soluble biomarkers indicates the occurrence of active changes in the
underlying disease processes. Recently, the OMERACT group has undertaken the task of
developing validation criteria for biomarkers. Validated biomarkers will be considered
reliable surrogate measures of radiological endpoints. C Reactive Protein (CRP) has recently
been validated using those newly developed criteria (ACR 2006). Noteworthy, the association
of CRP with damage endpoints appears to vary based on the use of different anti-rheumatic
medications. Other soluble biomarkers, which are being used in routine care, will be soon
evaluated against those same criteria.
Several other biomarkers of interest, including serum MMP-3, urinary CTX-II, serum
OPG/RANKL, serum CEC, and the CPII/C2C ratio, are being extensively evaluated in various
clinical studies. A recent study evaluated antibodies against modified citrullinated
vimentin (anti-MCV).
Predictors/prognostic markers indicate the presence of a change in the underlying disease
processes. However, their value is mainly related to their reliability at predicting future
changes, such as the clinical onset of the disease, the severity of the disease or
associated complications. In this respect, they are early indicators of future events.
Rheumatoid factors (RFs) are autoantibodies directed towards the Fc portions of IgG. RFs are
found in multiple immunoglobulin isotypes (IgE, IgM, IgA and IgG), however, IgM is the
isotype that is preferentially measured in clinical assays. RFs have long been associated
with the development and the severity of RA. The sensitivity and the specificity of RF in
the diagnosis of RA have been shown to be close to 60% and 79%, respectively. This is rather
low comparatively to other prognostic markers. This is mainly because RF is also detected in
normal healthy individuals as well as in various infections and other rheumatological
illnesses. As a result, its individual diagnostic value appears to be unsatisfactory. This
may be an issue in patients with early and undifferentiated arthritis. In this regard, IgM
RFs has been shown to be positive in 19.3% of RA patients prior to the onset of their
symptoms.
Antibodies targeting determinants resulting from the deamination of peptidylarginine to
peptidyl citrulline residues have recently received a great deal of attention. These include
antibodies directed against cyclic citrullinated peptide (anti-CCP) and antibodies targeting
in vivo citrullinated proteins, such as anti-keratin antibodies, antiperinuclear factor,
anti-citrullinated (pro)filaggrin and anti-Sa/citrullinated vimentin. The prognostic and
predictive values of anti-CCP antibodies have been extensively reviewed elsewhere. These
results indicate that anti-CCP antibodies are highly predictive of the future development of
RA in both healthy individuals and patients with undifferentiated arthritis. A more recent
study evaluated the sensitivity, specificity, and prognostic value of determination of
levels of anti-MCV as compared with anti-CCP in an inception cohort of patients with early
RA The findings showed that analysis of anti-MCV yields greater sensitivity and unchanged
specificity as compared with analysis of anti-CCP. And also appears to perform better than
anti-CCP in identifying poor radiographic prognosis in patients with early RA.
These observations suggest that different antibodies targeted against citrullinated agents
may differ in their ability to predict poor outcomes. Collectively, these observations
indicate that the predictive values of various predictors may be enhanced when combined with
other predictors/prognostic markers of the disease.
Primary Objectives
- To describe the prevalence of anti-MCV in an Irish RA population
- To assess the association of anti-MCV with RF and anti-CCP in this population.
- To assess the impact of known anti-CCP status (positive or negative) and anti-MCV on
clinical decision-making and the management of patients recently diagnosed with RA.
;
Observational Model: Cohort, Time Perspective: Prospective
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