Risk of hospitalization for heart failure in rheumatoid arthritis patients treated with etanercept and abatacept


To estimate biologic influence on heart failure (HF) risk in rheumatoid arthritis. Retrospective cohort (RECORD Study of Italian Society for Rheumatology) study on administrative healthcare databases. We identified 2527 patients treated with either etanercept (n = 1690) or abatacept (n = 837). HF incidence rate was higher in the abatacept cohort than in the etanercept cohort with a 2.38 (95% CI 1.08–5.27) crude competing risk HR (SHR) for abatacept of developing HF, not confirmed after adjustment for prespecified confounders (SHR 1.43; 95% CI 0.51–3.98). Abatacept, compared to etanercept, is prescribed to patients with a worse cardiovascular profile but does not increase the risk of developing HF, when confounding factors are accounted for.

This is a preview of subscription content, log in to check access.


  1. 1.

    van Halm VP, Peters MJ, Voskuyl AE, Boers M, Lems WF, Visser M, Stehouwer CD, Spijkerman AM, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Smulders YM, Dijkmans BA, Nurmohamed MT (2009) Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRE Investigation. Ann Rheum Dis 68(9):1395–1400. https://doi.org/10.1136/ard.2008.094151

    Article  PubMed  Google Scholar 

  2. 2.

    Pinheiro FA, Souza DC, Sato EI (2015) A study of multiple causes of death in rheumatoid arthritis. J Rheumatol. https://doi.org/10.3899/jrheum.150166

    Article  PubMed  Google Scholar 

  3. 3.

    Schau T, Gottwald M, Arbach O, Seifert M, Schopp M, Neuss M, Butter C, Zanker M (2015) Increased prevalence of diastolic heart failure in patients with rheumatoid arthritis correlates with active disease, but not with treatment type. J Rheumatol 42(11):2029–2037. https://doi.org/10.3899/jrheum.141647

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL (2001) Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 103(16):2055–2059

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Levine B, Kalman J, Mayer L, Fillit HM, Packer M (1990) Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323(4):236–241. https://doi.org/10.1056/NEJM199007263230405

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JMW, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poor G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76(6):960–977. https://doi.org/10.1136/annrheumdis-2016-210715

    Article  Google Scholar 

  7. 7.

    Javed Q, Murtaza I (2013) Therapeutic potential of tumour necrosis factor-alpha antagonists in patients with chronic heart failure. Heart Lung Circ 22(5):323–327. https://doi.org/10.1016/j.hlc.2012.12.002

    Article  PubMed  Google Scholar 

  8. 8.

    Solomon DH, Rassen JA, Kuriya B, Chen L, Harrold LR, Graham DJ, Lewis JD, Lii J, Liu L, Griffin MR, Curtis JR (2013) Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonist. Ann Rheum Dis 72(11):1813–1818. https://doi.org/10.1136/annrheumdis-2012-202136

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Rubbert-Roth A (2012) Assessing the safety of biologic agents in patients with rheumatoid arthritis. Rheumatology (Oxford) 51(suppl 5):38-47. https://doi.org/10.1093/rheumatology/kes114

    Article  CAS  Google Scholar 

  10. 10.

    Generali E, Carrara G, Selmi C, Verstappen S, Zambon A, Bortoluzzi A, Scirè C (2018) Comparison of the risks of hospitalisation for cardiovascular events in patients with rheumatoid arthritis treated with tocilizumab and etanercept. Clin Exp Rheumatol 36(2):310–313

    PubMed  Google Scholar 

  11. 11.

    Kallikourdis M, Martini E, Carullo P, Sardi C, Roselli G, Greco CM, Vignali D, Riva F, Ormbostad Berre AM, Stolen TO, Fumero A, Faggian G, Di Pasquale E, Elia L, Rumio C, Catalucci D, Papait R, Condorelli G (2017) T cell costimulation blockade blunts pressure overload-induced heart failure. Nat Commun 8:14680. https://doi.org/10.1038/ncomms14680

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Carrara G, Scire CA, Zambon A, Cimmino MA, Cerra C, Caprioli M, Cagnotto G, Nicotra F, Arfe A, Migliazza S, Corrao G, Minisola G, Montecucco C (2015) A validation study of a new classification algorithm to identify rheumatoid arthritis using administrative health databases: case-control and cohort diagnostic accuracy studies. Results from the RECord linkage On Rheumatic Diseases study of the Italian Society for Rheumatology. BMJ Open 5(1):e006029. https://doi.org/10.1136/bmjopen-2014-006029

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Corrao G, Ghirardi A, Ibrahim B, Merlino L, Maggioni AP (2014) Burden of new hospitalization for heart failure: a population-based investigation from Italy. Eur J Heart Fail 16(7):729–736. https://doi.org/10.1002/ejhf.105

    Article  PubMed  Google Scholar 

  14. 14.

    Nevers T, Salvador AM, Grodecki-Pena A, Knapp A, Velazquez F, Aronovitz M, Kapur NK, Karas RH, Blanton RM, Alcaide P (2015) Left ventricular T-cell recruitment contributes to the pathogenesis of heart failure. Circ Heart Fail 8(4):776–787. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Selmi C, Ceribelli A, Naguwa SM, Cantarini L, Shoenfeld Y (2015) Safety issues and concerns of new immunomodulators in rheumatology. Expert Opin Drug Saf 14(3):389–399. https://doi.org/10.1517/14740338.2015.993605

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Silvagni E, Bortoluzzi A, Carrara G, Zanetti A, Govoni M, Scire CA (2018) Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases. BMJ Open 8(9):e021447. https://doi.org/10.1136/bmjopen-2017-021447

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Carrara G, Bortoluzzi A, Sakellariou G, Silvagni E, Zanetti A, Govoni M, Scire CA (2018) Risk of hospitalisation for serious bacterial infections in patients with rheumatoid arthritis treated with biologics. Analysis from the RECord linkage On Rheumatic Disease study of the Italian Society for Rheumatology. Clin Exp Rheumatol [Epub ahead of print]

  18. 18.

    Caprioli M, Carrara G, Sakellariou G, Silvagni E, Scire CA (2017) Influence of aromatase inhibitors therapy on the occurrence of rheumatoid arthritis in women with breast cancer: results from a large population-based study of the Italian Society for Rheumatology. RMD Open 3(2):e000523. https://doi.org/10.1136/rmdopen-2017-000523

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Buttgereit JWJB F (2016) Adverse events of glucocorticoids during treatment of rheumatoid arthritis: lessons from cohort and registry studies. Rheumatology 55(suppl 2):ii3–ii5. https://doi.org/10.1093/rheumatology/kew344

    Article  PubMed  Google Scholar 

  20. 20.

    Ajeganova S, Svensson B, Hafstrom I, Group BS (2014) Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial. BMJ Open 4(4):e004259. https://doi.org/10.1136/bmjopen-2013-004259

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information




EG, GC, AB, CS, CAS, MK, GC designed the idea, designed and supervised the project. EG, CS, GC, CAS, AB contributed to data analysis. EG, GC, AB CS, CAS, MK, GC critically reviewed and provided valuable input. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Carlo Selmi.

Ethics declarations

Conflict of interest

EG, GC, MK, GC, AB, CAS have none to declare; Carlo Selmi has been consulting for BMS and Pfizer.

Ethical approval

The present work was approved by IRB of University of Pavia, Italy (deliberation of 12/03/2012).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Generali, E., Carrara, G., Kallikourdis, M. et al. Risk of hospitalization for heart failure in rheumatoid arthritis patients treated with etanercept and abatacept. Rheumatol Int 39, 239–243 (2019). https://doi.org/10.1007/s00296-018-4196-9

Download citation


  • Cardiovascular
  • Epidemiology
  • DMARDs
  • Biologic