Cardiovascular Diseases Clinical Trial
Official title:
The Effect of Interruption of TNFi on Endothelial Function in Patients With Rheumatoid Arthritis
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Treatment with TNFalpha inhibitors (TNFi) improve endothelial function in patients with RA. Discontinuation of TNFi could therefore worsen endothelial function even in the absence of recurrence of systemic inflammation or reactivation of arthritis. If stopping TNFi results in worsening of endothelial function this would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events.
This increased risk is thought to be driven by inflammation-induced endothelial dysfunction,
an initial step in atherogenesis. Both systemic as well as local (intra-arterial) treatment
with anti-TNF-antibody therapy improves endothelial function in patients with vasculitis or
RA as reflected by the vasodilator response to intra-arterially infused acetylcholine. Also
other vascular functions that are (at least partially) endothelium-dependent such as
flow-mediated dilation of the brachial artery and pulse wave velocity are improved when
active RA patients are being treated with methotrexate plus TNFi, i.e. infliximab or
etanercept. ( Therefore one may hypothesize that when TNFi therapy is stopped, endothelial
function may worsen even in the absence of recurrence of systemic inflammation or
reactivation of arthritis. Endothelial function tests are a marker of long-term
cardiovascular mortality. If stopping TNFi results in worsening of endothelial function this
would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal.
These findings would indicate an important drawback for stopping TNFi in RA patients.
To date it is unclear whether the worsening of endothelial function occurs within half a
year following the (successful) cessation of TNFi, whether this decline occurs
simultaneously, or prior to RA exacerbation and whether this deterioration process is
delayed by additional use of statin and/or ACEi.
To improve cardiovascular prognosis in RA significantly it is important to increase our
knowledge regarding these processes.
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Observational Model: Case Control, Time Perspective: Prospective
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