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 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

The primary objective of the study is to investigate the effect of interruption
of anti-TNF-alpha therapy on endothelium dependent and independent vasodilation
and the effect of intra-arterial infusion of infliximab on the endothelium
dependent and independent vasodilation.

This study is a substudy of the POEET ( Potential optimalisation of Expediency
and Effectiveness of TNF blockers) trial, a open label randomized controlled
study design where patients (n=1000) are randomized to discontinue TNF blocking
therapy or continue all anti-rheumatic medication including TNF blocking
therapy.

In patients included in this substudy, the forearm vasodilator response to
acetylcholine and nitroprusside (infused in brachial artery) will be assessed.

During the 6 month follow-up period all patients will be monitored according to
the POEET-protocol: recording of concomitant medication, co-morbidity and DAS.
In patients who experience exacerbation of RA before the end of the study (6
months) which requires additional disease modifying drugs (including restart of
TNFi-therapy) the intra-arterial procedure will be repeated prior to restart of
this therapy.

Intra-arterial infliximab 20 microgram/dl forearm volume /min during 80
minutes, during venous occlusion plethysmography

Patients will not benefit from participating in this study. Plethysmography
will cause numbness and discomfort in both hands due to inflation of the
wrist-cuffs. This is temporarily and completely reversible. The two experiments
will take approximately 4 hours each. Finally, bruising may occur after
venapuncture or removal of the intra-arterial 27 G needle. Measures like
pressure bandage will be taken to minimize the risk. Sometimes there can be
some numbness or tingling of fingers due to a hematoma caused by the
intra-arterial cannule for a few weeks after the experiment.No side effects are
expected of the infused agents.