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Original article
Comparative effect of tumour necrosis factor inhibitors versus other biological agents on cardiovascular risk-associated biomarkers in patients with rheumatoid arthritis
  1. Alexandre Virone1,
  2. Jean-Philippe Bastard2,3,
  3. Soraya Fellahi2,3,
  4. Jacqueline Capeau3,
  5. Stéphanie Rouanet4,
  6. Jean Sibilia5,
  7. Philippe Ravaud6,
  8. Francis Berenbaum1,3,
  9. Jacques-Eric Gottenberg5 and
  10. Jérémie Sellam1,3
  11. on behalf of Club Rhumatismes Inflammation-IMIDIATE network
  1. 1Rheumatology Department, Hôpital Saint-Antoine, Assistance Publique - Hopitaux de Paris (AP-HP), Paris, France
  2. 2Biochemistry Department, Hôpital Tenon, AP-HP, Paris, France
  3. 3Faculty of Medicine Sorbonne Université, CRSA INSERM UMRS_938, Paris, France
  4. 4StatEthic, Levallois-Perret, France
  5. 5Rheumatology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  6. 6Epidemiology and Statistics Research Centre, Inserm UMR 1153, Paris Descartes University, Paris, France
  1. Correspondence to Dr Jérémie Sellam; jeremie.sellam{at}


Background To comparatively investigate the differential effect of second-line tumour necrosis factor inhibitors (TNFis) versus other biological agents on cardiovascular disease (CVD) risk-associated biomarkers in patients with rheumatoid arthritis (RA).

Methods We evaluated the serum levels of lipoprotein-associated apoproteins ApoA1 and ApoB100 and lipoprotein(a) (Lp(a)) and the leptin/adiponectin ratio (LAR) as an insulin resistance proxy in patients with RA from the Rotation Or Change (ROC) trial treated with either a second-line TNFi or another biologic (tocilizumab (TCZ), rituximab or abatacept) at baseline and week 24. We compared the changes in biomarker levels in each group and according to the EULAR response.

Results Of the 300 patients enrolled in the ROC trial, 203 were included in the study, including 96 in the second-line TNFi group and 107 in the other biological group. The measured biomarkers did not deteriorate between baseline and week 24 regardless of the group. A greater improvement in the LAR was noted in the other biological group (median (IQR) −0.12 ng/µg (−0.58 to 0.31) vs 0.04 (−0.19 to 0.43), p=0.033), and a greater improvement in the Lp(a) level was observed following treatment with TCZ than with a TNFi (−0.05 g/L (−0.11 to −0.01) vs −0.01 g/L (−0.02 to 0.01), p<0.001). When considering the patients’ responses to treatment, improved biomarkers were mainly observed in the EULAR responders in each treatment group.

Conclusions TNFis and non-TNFis were neutral on improved CVD risk-associated biomarkers in patients with RA insufficiently controlled by TNFis. TCZ could be associated with a better improvement concerning Lp(a) and LAR than TNFis. This improvement could be related to a good therapeutic response, thereby supporting the need of good control of RA.

Trial registration number Identifier NCT01000441, registered on 22 October 2009.

  • cardiovascular risk
  • rheumatoid arthritis
  • biological agents
  • adipokine
  • apolipoprotein

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  • Presented at 2017 American College of Rheumatology meeting

  • Twitter @jeremsellam; @Larhumato

  • Contributors PR, JSi and J-EG were involved in the conception and design of the ROC trial. JSe, AV, JC and J-EG were involved in the conception of this ancillary study. J-PB and SF performed biomarker assessments. AV, JSe and SR designed and performed the statistical analysis. AV and JSe wrote the initial draft of the manuscript. All authors were involved in the analysis and interpretation of the data. All authors drafted the manuscript and revised it critically. All authors approved the final version to be submitted for publication, and all authors agreed to be accountable for all aspects of the work.

  • Funding The ROC trial was sponsored by the French Ministry of Health (Programme Hospitalier de Recherche Clinique National 2009/4507 EUDRACT No: 2009-013482-26) and promoted by the Direction de la Recherche Clinique et de l’Innovation, Strasbourg University Hospital.

  • Competing interests JSe: consulting fees and symposia: BMS, Janssen, Menarini, MSD, Pfizer, Roche France, Fresenius Kabi, Lilly, Sandoz and Abbvie; research grants: Roche France and Pfizer. JC: fees for academic conferences by Janssen, MSD, ViiV Healthcare, Gilead, Chugai and Novartis. JSi: fees from Abbvie, Bristol-Myers Squibb, Merck, Sharp, Dohme, UCB, Pfizer, Roche, Novartis, GlaxoSmithKline, Actelion, Amgen and Hospira. FB: current or past board member of Pfizer, Abbvie, Merck Serono, Servier, Expanscience, Sanofi, UCB, Novartis, Biogaran, Biogen and Proxymagen; consultant for Janssen and Flexion; received grants from Servier and TRB Chemedica; and is on speaker’s bureau for Servier and Abbvie. J-EG: consulting fees and research grants: Abbvie, BMS, MSD, UCB, Roche and Pfizer.

  • Patient consent for publication Not required.

  • Ethics approval The institutional review board of the Comité de Protection des Personnes-Est-1, Strasbourg, France, approved the study and all patients provided written informed consent after receiving oral and written information.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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