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POET-VEF: Interruption of TNFinhibitors and Endothelial Function

Sponsor
Radboud University Medical Center (Other)
Overall Status
Unknown status
CT.gov ID
NCT02130076
Collaborator
(none)
48
Enrollment
27
Duration (Months)

Study Details

Study Description

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 Intervention/Treatment Phase

    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

    Study Type:
    Observational
    Anticipated 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 :
    Sep 1, 2012
    Anticipated Primary Completion Date :
    Dec 1, 2014
    Anticipated Study Completion Date :
    Dec 1, 2014

    Arms and Interventions

    Arm Intervention/Treatment
    Stop

    Patients with stable RA stopping TNF inhibition
    Continue

    Patients with stable RA continuing TNFi therapy

    Outcome Measures

    Primary Outcome Measures

    1. Response to acetylcholine [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 [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 [6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Radboud University Medical Center

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    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
    Last Update Posted:
    May 2, 2014
    Last Verified:
    Apr 1, 2014
    Additional relevant MeSH terms:
    Arthritis
    Cardiovascular Diseases

    Study Results

    No Results Posted as of May 2, 2014