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

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Abstract

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

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Funding

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.

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Author notes

  1. Matthijs Janssen & Tim L. Jansen

    Present address: VieCuri Medical Centre, Venlo, The Netherlands

Authors and Affiliations

  1. Department of General Internal Medicine, Radboudumc, Nijmegen, The Netherlands

    Gerard A. Rongen

  2. Department of Pharmacology-Toxicology, Radboud University Medical Center, 149, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Gerard A. Rongen

  3. Deparment of Rheumatology, Radboudumc, Nijmegen, The Netherlands

    Iris van Ingen

  4. Department of Rheumatology, Maasstadziekenhuis, Rotterdam, The Netherlands

    Marc Kok

  5. Department of Rheumatology, Medical Spectre Enschede, Enschede, The Netherlands

    Harald Vonkeman

  6. Department Rheumatology, VieCuri Medical Centre, Venlo, The Netherlands

    Matthijs Janssen

Authors
  1. Gerard A. Rongen
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  2. Iris van Ingen
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  3. Marc Kok
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  6. Tim L. Jansen
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Corresponding author

Correspondence to Gerard A. Rongen.

Ethics declarations

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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Rongen, G.A., van Ingen, I., Kok, M. et al. Vasodilator function worsens after cessation of tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis only if a flare occurs. Clin Rheumatol 37, 909–916 (2018). https://doi.org/10.1007/s10067-017-3961-6

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  • DOI: https://doi.org/10.1007/s10067-017-3961-6

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