Clinical trial NCT02130076: Interruption of TNFinhibitors and Endothelial Function
Official title: The Effect of Interruption of TNFi on Endothelial Function in Patients With Rheumatoid Arthritis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Reumatoid Arthritis
Cardiovascular Diseases
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2014-05-02
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with stable rheumatoid arthritis who are included in another study (POEET) to stop or continue their TNFi therapy.

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Informed consent for POEET trial and this additional study
* On stable medication (except for TNFi-therapy)

Exclusion Criteria:

* Uncontrolled hypertension (RR \> 140/90 mmHg average of three measurements at screening after 5 minutes of supine rest)
* Diabetes mellitus
* Heart failure or any other cardiovascular disease that is expected to induce changes in cardiovascular medication during the study period.
* Expected to start or change medication that can alter endothelial function (lipid lowering drugs, blood pressure lowering drugs, NSAIDs, immunosuppressive therapy other than TNFi drugs)

Primary outcomes:
measure: Response to acetylcholine
timeFrame: 6 months
Secondary outcomes:
measure: TNFi withdrawal and response to nitroprusside
timeFrame: 6 months
measure: VCAM and SCAM
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
References:
citation: Rongen GA, van Ingen I, Kok M, Vonkeman H, Janssen M, Jansen TL. Vasodilator function worsens after cessation of tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis only if a flare occurs. Clin Rheumatol. 2018 Apr;37(4):909-916. doi: 10.1007/s10067-017-3961-6. Epub 2018 Jan 7.