To measure the effect of lowering or stopping biologicals on various coagulation parameters in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Additional blood samples will be taken during three consecutive visits to the
'biopoli'. These will be stored at a temperature of -80 ° C. The following
biomarkers of coagulation activation will be determined:
F1 + 2, prothrombin fragments1 and 2
TAT, thrombin-antithrombin complexes
PAP, plasmin-a2-antiplasmin inhibitor complex
TGA, trombin generation analysis
Secondary outcome
Not applicable.
Background summary
Inflammation and cardiovascular risk
RA is associated with increased morbidity and mortality, primarily as a result
of cardiovascular complications. This increased risk is only partly explained
by an increased prevalence of traditional risk factors such as dyslipidemia,
hypertension, smoking, obesity and diabetes mellitus. In addition to these
traditional cardiovascular risk factors, inflammation contributes significantly
to the increased cardiovascular risk. Several markers of active inflammation,
such as CRP and disease activity scores have been associated with
cardiovascular risk. This relationship between inflammation and increased
cardiovascular risk is not only present in RA, but also in other rheumatic
diseases such as AS and PsA.
Pro-thrombotic phenomena
Another important link between inflammation and risk of cardiovascular disease
is formed by increased clotting activity. Inflammation can lead to the
activation of the coagulation system and vice-versa activity of the coagulation
system can also influence inflammatory activity. Previous studies reported
various blood parameters that reflect an increased coagulation activation in
patients with RA. For example, elevated levels of thrombin-anti-thrombin
complexes (TAT), prothrombin fragments 1 and 2 (F1 + F2),
plasmin-a2-antiplasmin inhibitor complex (PAP), D-dimer an increased number of
platelets have been found in patients with active disease. Impaired
fibrinolysis in combination with an elevated antithrombin levels have also been
reported in RA. In summary, RA (and other autoimmune inflammatory disorders
such as AS and PsA), can be regarded as a pro-thrombotic state, which partially
explains why patients with RA have an increased risk of thromboembolic
cardiovascular events.
Effects of anti-rheumatic therapy
Inflammatory cytokines, particularly TNF-* and interleukins such as
interleukin-6 (IL-6), are able to stimulate endothelial cells, which leads to a
pro-thrombotic state. Cytokines induce the expression of tissue factor, inhibit
the protein C system and inhibit fibrinolysis, thereby promoting a
pro-thrombotic state. It is therefore very likely that biologicals have a
beneficial effect on the hemostatic status in auto-inflammatory diseases.
Biologicals indeed result in a reduction of cardiovascular risk in patients
with RA. Up to now, only small studies have examined the effects of biological
agents on coagulation factors, and they suggest an association between therapy
with biologicals and normalization of thrombotic biomarkers.
Today biologicals are increasingly being tapered, but how this effects the
coagulation activation is unknown. Given the mounting evidence of increased
cardiovascular morbidity and mortality in patients with rheumatic disease,
treatment strategies should not only focus on relieving symptoms, but should
also have a beneficial effect on cardiovascular risk factors, such as clotting
activation. Although modest, there are indications that biologicals have a
beneficial effect on the haemostatic status. Unfavorable changes in haemostatic
markers can thus (re)occurt as the biological is tapered or stopped.
Study objective
To measure the effect of lowering or stopping biologicals on various
coagulation parameters in patients with rheumatoid arthritis, ankylosing
spondylitis, and psoriatic arthritis.
Study design
In Reade, all patients using biologicals are seen regularly at the 'biopoli',
were they are monitored systematically. In patients with disease activity, the
dosage of the biological is gradually reduced, and if possible, the biological
is completely stopped. During this tapering period patients are seen regularly
at our biopoli, and during that visits disease activity and current medication
use (among others) are registered. Furthermore, these visits include laboratory
evaluations. In order to study biomarkers of coagulation, we are going to draw
a small extra amount of blood on some of this visits, consisting of 2 tubes (2
x 4.5 mL). This extra blood collection is combined with the blood tests that
are done already, so that the additional load is minimal for the patient.
Additional blood tests will take place on three occasions: prior to tapering of
the biological, and after 6 and 12 months after dose reduction.
Study burden and risks
Not applicable.
Dr. Jan van Breemenstraat 2
Amsterdam 1056 AB
NL
Dr. Jan van Breemenstraat 2
Amsterdam 1056 AB
NL
Listed location countries
Age
Inclusion criteria
Diagnosis RA, AS or PsA
Use of biologicals
Reducing biological due to low disease activity (to be determined by the treating rheumatologist)
Exclusion criteria
Insufficient understanding of the Dutch language to be able to sign informed consent
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 | NL57580.048.16 |