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Tumor Necrosis Factor Alpha Inhibitors and Cardiovascular Risk in Rheumatoid Arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an increased risk of cardiovascular events, due to the complex interplay between traditional and disease-related risk factors. Chronic inflammation and persistent disease activity are the key determinants of this risk, but despite great improvement in the disease management and prognosis, cardiovascular events are still the main cause of morbidity and mortality in RA cohorts1. In the last decades, the advent of new biological and targeted-synthetic DMARDs was accompanied by an improvement in disease activity control, but the role of each class of drugs on CVD risk is still a matter a debate. Since their approval for RA treatment, tumor necrosis factor alpha (TNFα) inhibitors have been widely investigated to better understand their effects on cardiovascular outcomes. The hypothesis that the reduction of chronic inflammation with any treatment may reduce the cardiovascular risk has been recently confuted by the direct comparison of TNFα-inhibitors and JAK inhibitors in patients with RA and coexisting risk factors for cardiovascular disease. The aim of this literature review is to add to the available evidence to analyze the relationship between TNFα-inhibitors and CVD risk in patients with RA and also provide some clinical scenarios to better explain the treatment dilemmas. In particular, while data on major cardiovascular events and thromboembolism seem consistent with an inflammation-mediated benefit with TNFα-inhibitors, there remain concerns about the use of this class of bDMARDs in patients with chronic heart failure.

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Authors and Affiliations

  1. Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy

    Nicoletta Luciano, Elisa Barone & Carlo Selmi

  2. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy

    Elisa Barone & Carlo Selmi

  3. Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA

    Suraj Timilsina & M. Eric Gershwin

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Conception and design: NL, EB, CS, MEG and ST: literature evaluation and critical discussion: NL, EB, CS, MEG and ST; manuscript initial preparation: NL, EB.

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Nicoletta Luciano received speakers fees (AbbVie, Eli-Lilly, Galapagos, Novartis) Carlo Selmi received consulting / speakers fee (AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA Pharma - Recordati, Galapagos, Janssen, Novartis, Pfizer, Recordati, SOBI) and research support (AbbVie, Amgen, Janssen, Novartis, Pfizer)

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Luciano, N., Barone, E., Timilsina, S. et al. Tumor Necrosis Factor Alpha Inhibitors and Cardiovascular Risk in Rheumatoid Arthritis. Clinic Rev Allerg Immunol 65, 403–419 (2023). https://doi.org/10.1007/s12016-023-08975-z

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