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Interruption of TNFinhibitors and Endothelial Function (POET-VEF)

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ClinicalTrials.gov Identifier: NCT02130076
Recruitment Status : Unknown
Verified April 2014 by G. Rongen, Radboud University Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : May 2, 2014
Last Update Posted : May 2, 2014
Sponsor:
Information provided by (Responsible Party):
G. Rongen, Radboud University Medical Center

Study Description
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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

Condition or disease
Reumatoid Arthritis Cardiovascular Diseases

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.

Study Design
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Study Type : Observational
Estimated Enrollment : 48 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: The Effect of Interruption of TNFi on Endothelial Function in Patients With Rheumatoid Arthritis
Study Start Date : September 2012
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis

Groups and Cohorts
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Group/Cohort
Stop
Patients with stable RA stopping TNF inhibition
Continue
Patients with stable RA continuing TNFi therapy


Outcome Measures
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Primary Outcome Measures :
  1. Response to acetylcholine [ Time Frame: 6 months ]
    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.


Secondary Outcome Measures :
  1. TNFi withdrawal and response to nitroprusside [ Time Frame: 6 months ]
    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.

  2. VCAM and SCAM [ Time Frame: 6 months ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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)
Contacts and Locations
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No Contacts or Locations Provided
More Information
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: G. Rongen, Prof dr G Rongen, Radboud University Medical Center
ClinicalTrials.gov Identifier: NCT02130076    
Other Study ID Numbers: IMM11-0103
First Posted: May 2, 2014    Key Record Dates
Last Update Posted: May 2, 2014
Last Verified: April 2014
Additional relevant MeSH terms:
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Arthritis
Cardiovascular Diseases
Joint Diseases
Musculoskeletal Diseases