Interruption of TNFinhibitors and Endothelial Function

Cardiovascular Diseases Clinical Trial

— POET-VEF  

Official title:

The Effect of Interruption of TNFi on Endothelial Function in Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02130076
• Other study ID #: IMM11-0103
• Status: Active, not recruiting
• Phase: N/A
• First received: January 8, 2013
• Last updated: May 1, 2014
• Start date: September 2012
• Est. completion date: December 2014

Study information

• Verified date: April 2014
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Arthritis
• Cardiovascular Diseases
• Reumatoid Arthritis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to acetylcholine	The primary endpoint is the interaction between TNFi-withdrawal and the vasodilator response to acetylcholine expressed as difference in FBF between the withdrawal group and the continuing group.	6 months	No
Secondary	TNFi withdrawal and response to nitroprusside	Secondary endpoints are the interaction between TNFi-withdrawal and the vasodilator response to nitroprusside (expressed as difference in FBF between the withdrawal group and the continuing group). The response to SNP serves as an internal vasodilator control to assess potential endothelium-independent effects of TNFi-withdrawal on the response to acetylcholine.	6 months	No
Secondary	VCAM and SCAM		6 months	No