Clinical Rheumatology

, Volume 37, Issue 4, pp 909–916 | Cite as

Vasodilator function worsens after cessation of tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis only if a flare occurs

  • Gerard A. Rongen
  • Iris van Ingen
  • Marc Kok
  • Harald Vonkeman
  • Matthijs Janssen
  • Tim L. Jansen
Original Article


Vasodilator function is reported to be reduced in rheumatoid arthritis (RA), and is considered an early sign of vascular dysfunction, which is normalised by TNF inhibitors (TNFi). To optimise cost-effectiveness, tapering or interruption of TNFi therapy in established RA patients is advocated. We explored whether cessation of TNFi results in impaired vasodilator function and whether this relates to the development of a Disease Activity Score (DAS28)-based flare. Forty-one patients were assessed for eligibility as RA with at least 12 months of low disease activity (based on 28 joint counts); 35 enrolled into the randomised study: 8 were randomised to continue, 27 to stopping TNFi. Forearm vasodilation to acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed before cessation of TNFi therapy (visit 1) and 6 months after (dis)continuation of TNFi or at flare (based on DAS28) whichever came first (visit 2). None of the patients who continued their TNFi therapy flared. Eight out of 22 patients who stopped TNFi therapy flared. The vasodilator response to ACh and SNP was reduced significantly in patients who experienced a flare of RA: In patients who did not experience a flare, the vasodilator response to ACh or SNP was not significantly affected. Vasodilator function is reduced after cessation of TNFi, but only when RA reactivates, indicating that early vasodilator dysfunction is a consequence rather than a cause of systemic inflammation in RA and not specifically related to inhibition of TNFα signalling. Without close monitoring, microvascular damage can occur after TNFi interruption with potential devastating implications for cardiovascular health. Trial registration: NCT02130076


Rheumatoid arthritis TNF inhibitors Vasodilator function Flow mediated vasodilation Vascular smooth cells Endothelial vasodilation Stopping TNF inhibitor 


Funding information

Funding for this vascular substudy of the POEET trial by Abbvie is gratefully acknowledged. The POEET trial was funded by The Netherlands Organisation for Health Research and Development (ZonMw) and the Government of The Netherlands, Ministry of Health, Welfare, and Sport.

Compliance with ethical standards

This study was approved by the institution medical ethics committee (CMO Arnhem/Nijmegen; registration number: CMO 2012/153). All study procedures were performed according to GCP and the declaration of Helsinki.

Conflict of interest disclosure statement

TJ has received fees for advisory boards over the last 5 years from Abbvie, Ardea, Astra Zeneca, BMS, Celgene, Eli Lilly, Menarini, Novartis, Pfizer, Roche, Sanofi Genzyme; TJ has received fees for lectures from Abbvie, BMS, Menarini, Grunenthal. No further disclosures were reported.


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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Gerard A. Rongen
    • 1
    • 2
  • Iris van Ingen
    • 3
  • Marc Kok
    • 4
  • Harald Vonkeman
    • 5
  • Matthijs Janssen
    • 6
    • 7
  • Tim L. Jansen
    • 7
  1. 1.Department of General Internal MedicineRadboudumcNijmegenThe Netherlands
  2. 2.Department of Pharmacology-ToxicologyRadboud University Medical CenterNijmegenThe Netherlands
  3. 3.Deparment of RheumatologyRadboudumcNijmegenThe Netherlands
  4. 4.Department of RheumatologyMaasstadziekenhuisRotterdamThe Netherlands
  5. 5.Department of RheumatologyMedical Spectre EnschedeEnschedeThe Netherlands
  6. 6.Department RheumatologyVieCuri Medical CentreVenloThe Netherlands
  7. 7.VieCuri Medical CentreVenloThe Netherlands

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