Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology and Hepatology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Ophthalmology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
ASH 2024 Annual Meeting 2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Women’s Health Knowledge Hub Advances in Alzheimer’s

Navigating neuroimaging in Alzheimer disease care

PET imaging is playing an increasingly critical role in managing AD, but how can you effectively integrate it into clinical practice? Our expert-led program will empower you with practical strategies and real-world case studies.

This content is intended for healthcare professionals outside of the UK.
ADVANCED SEARCH
Log in
Top
Rheumatology and Therapy
Published in:

Open Access 28-02-2025 | Arthritis | Review

The Cardiovascular Safety of Tumour Necrosis Factor Inhibitors in Arthritic Conditions: A Structured Review with Recommendations

Authors: Jérôme Avouac, Hafid Ait-Oufella, Caroline Habauzit, Salim Benkhalifa, Bernard Combe

Published in: Rheumatology and Therapy | Issue 2/2025

Login to get access

Abstract

There is accumulating evidence that inflammation is a key driver of atherosclerosis development and thrombotic complications. This pathophysiological mechanism explains, at least in part, the increased cardiovascular risk of patients with immune-mediated arthritis. Experimental and clinical studies have shown that tumour necrosis factor (TNF) plays a pathological role in both vascular and joint diseases, suggesting that TNF inhibitors (TNFis) may limit cardiovascular events in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or spondyloarthritis (SpA). This review summarizes studies exploring the effects of TNFis on cardiovascular outcomes in patients with RA, PsA or SpA. Clinical studies suggest that TNFis reduce vascular inflammation and may improve (or prevent worsening of) endothelial dysfunction and arterial stiffness. There is evidence that TNFis reduce the incidence of cardiovascular events in patients with inflammatory arthritis compared with non-biological treatments, particularly in patients with rheumatoid arthritis. Fewer studies have compared the effects of different classes of biological therapy on outcomes, but found no significant difference in the risk of cardiovascular events between patients taking TNFis and other biological therapy. In contrast, patients at high cardiovascular risk may derive greater benefit from a TNFi than from a Janus kinase inhibitor (JAKi). The cardiovascular impact of JAKis is still under debate, with a recent safety warning. Targeted control of inflammation is a key strategy to reduce the risk of major adverse cardiovascular events in patients with inflammatory arthritis. Cardiovascular evaluation and risk stratification, using a multidisciplinary approach involving rheumatology and cardiology teams, are recommended to guide optimal immunomodulatory treatment.
Appendix
Available only for authorised users
Literature
1.
Kong P, Cui ZY, Huang XF, Zhang DD, Guo RJ, Han M. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduct Target Ther. 2022;7:131.PubMedPubMedCentralCrossRef
2.
Ait-Oufella H, Sage AP, Mallat Z, Tedgui A. Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis. Circ Res. 2014;114:1640–60.PubMedCrossRef
3.
Zhao Q, Hong D, Zhang Y, Sang Y, Yang Z, Zhang X. Association between anti-TNF therapy for rheumatoid arthritis and hypertension: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2015;94: e731.PubMedCrossRef
4.
Jaiswal V, Batra N, Dagar M, et al. Inflammatory bowel disease and associated cardiovascular disease outcomes: a systematic review. Medicine (Baltimore). 2023;102: e32775.PubMedCrossRef
5.
Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012;71:1524–9.PubMedCrossRef
6.
Kim JH, Choi IA. Cardiovascular morbidity and mortality in patients with spondyloarthritis: a meta-analysis. Int J Rheum Dis. 2021;24:477–86.PubMedCrossRef
7.
Polachek A, Touma Z, Anderson M, Eder L. Risk of cardiovascular morbidity in patients with psoriatic arthritis: a meta-analysis of observational studies. Arthritis Care Res (Hoboken). 2017;69:67–74.PubMedCrossRef
8.
Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2019;71:1599–613.PubMedPubMedCentralCrossRef
9.
Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3–18.PubMedCrossRef
10.
Singh JA, Guyatt G, Ogdie A, et al. Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Rheumatol. 2019;71:5–32.PubMedCrossRef
11.
Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73:924–39.PubMedCrossRef
12.
Perrone V, Giacomini E, Sangiorgi D, et al. Treatment pattern analysis and health-care resource consumption on patients with psoriatic arthritis or ankylosing spondylitis treated with biological drugs in a Northern Italian region. Ther Clin Risk Manag. 2020;16:509–21.PubMedPubMedCentralCrossRef
13.
Mease PJ, Stryker S, Liu M, et al. Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conventional synthetic disease-modifying antirheumatic drug therapy and enrolled in a North American clinical registry. Arthritis Res Ther. 2021;23:236.PubMedPubMedCentralCrossRef
14.
Fletcher A, Lassere M, March L, et al. Patterns of biologic and targeted-synthetic disease-modifying antirheumatic drug use in rheumatoid arthritis in Australia. Rheumatology (Oxford). 2022;61:3939–51.PubMedCrossRef
15.
Matsson A, Solomon DH, Crabtree MM, Harrison RW, Litman HJ, Johansson FD. Patterns in the sequential treatment of patients with rheumatoid arthritis starting a biologic or targeted synthetic disease-modifying antirheumatic drug: 10-year experience from a US-based registry. ACR Open Rheumatol. 2024;6:5–13.PubMedCrossRef
16.
Murage MJ, Princic N, Park J, et al. Treatment patterns and health care costs among patients with psoriatic arthritis treated with biologic or targeted synthetic disease-modifying antirheumatic drugs. J Manag Care Spec Pharm. 2022;28:206–17.PubMed
17.
Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316–26.PubMedCrossRef
18.
Avouac J, Fogel O, Hecquet S, et al. Recommendations for assessing the risk of cardiovascular disease and venous thromboembolism before the initiation of targeted therapies for chronic inflammatory rheumatic diseases. Joint Bone Spine. 2023;90: 105592.PubMedCrossRef
19.
Lordan R, Tsoupras A, Zabetakis I. Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: potential role of antiplatelet agents. Blood Rev. 2021;45: 100694.PubMedCrossRef
20.
Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006;86:515–81.PubMedCrossRef
21.
Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent advances on the role of cytokines in atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31:969–79.PubMedCrossRef
22.
Jang DI, Lee AH, Shin HY, et al. The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. Int J Mol Sci. 2021;22:2719.PubMedPubMedCentralCrossRef
23.
Urschel K, Cicha I. TNF-α in the cardiovascular system: from physiology to therapy. Int J Interferon Cytokine Mediat Res. 2015;7:9–25.
24.
Ohta H, Wada H, Niwa T, et al. Disruption of tumor necrosis factor-α diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis. 2005;180:11–7.PubMedCrossRef
25.
Canault M, Peiretti F, Mueller C, et al. Exclusive expression of transmembrane TNF-α in mice reduces the inflammatory response in early lipid lesions of aortic sinus. Atherosclerosis. 2004;172:211–8.PubMedCrossRef
26.
Myasoedova E, Crowson CS, Kremers HM, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011;70:482–7.PubMedCrossRef
27.
Barath P, Fishbein MC, Cao J, Berenson J, Helfant RH, Forrester JS. Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol. 1990;65:297–302.PubMedCrossRef
28.
Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor-α and increased risk of recurrent coronary events after myocardial infarction. Circulation. 2000;101:2149–53.PubMedCrossRef
29.
Yuan S, Carter P, Bruzelius M, et al. Effects of tumour necrosis factor on cardiovascular disease and cancer: a two-sample Mendelian randomization study. EBioMedicine. 2020;59: 102956.PubMedPubMedCentralCrossRef
30.
Shen J, Shang Q, Tam LS. Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis. Transl Res. 2016;167:138–51.PubMedCrossRef
31.
Capria A, De Nardo D, Baffetti FR, et al. Long-term anti-TNF-alpha treatments reverse the endothelial dysfunction in rheumatoid arthritis: the biological coherence between synovial and endothelial inflammation. Int J Immunopathol Pharmacol. 2010;23:255–62.PubMedCrossRef
32.
Mazzoccoli G, Notarsanto I, de Pinto GD, et al. Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psoriatic and rheumatoid arthritis patients. Intern Emerg Med. 2010;5:495–500.PubMedCrossRef
33.
Végh E, Kerekes G, Pusztai A, et al. Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis. Rheumatol Int. 2020;40:427–36.PubMedCrossRef
34.
Ortolan A, Ramonda R, Lorenzin M, et al. Subclinical atherosclerosis evolution during 5 years of anti-TNF-alpha treatment in psoriatic arthritis patients. Clin Exp Rheumatol. 2021;39:158–61.PubMedCrossRef
35.
Ursini F, Leporini C, Bene F, et al. Anti-TNF-alpha agents and endothelial function in rheumatoid arthritis: a systematic review and meta-analysis. Sci Rep. 2017;7:5346.PubMedPubMedCentralCrossRef
36.
Deyab G, Hokstad I, Whist JE, et al. Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis. Arthritis Res Ther. 2017;19:232.PubMedPubMedCentralCrossRef
37.
Galarraga B, Belch JJ, Pullar T, Ogston S, Khan F. Clinical improvement in rheumatoid arthritis is associated with healthier microvascular function in patients who respond to antirheumatic therapy. J Rheumatol. 2010;37:521–8.PubMedCrossRef
38.
Batko B, Maga P, Urbanski K, et al. Microvascular dysfunction in ankylosing spondylitis is associated with disease activity and is improved by anti-TNF treatment. Sci Rep. 2018;8:13205.PubMedPubMedCentralCrossRef
39.
Tyrrell PN, Beyene J, Feldman BM, McCrindle BW, Silverman ED, Bradley TJ. Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol. 2010;30:1014–26.PubMedCrossRef
40.
Evans MR, Escalante A, Battafarano DF, Freeman GL, O’Leary DH, del Rincón I. Carotid atherosclerosis predicts incident acute coronary syndromes in rheumatoid arthritis. Arthritis Rheum. 2011;63:1211–20.PubMedPubMedCentralCrossRef
41.
Blanken AB, Raadsen R, Agca R, van Sijl AM, Smulders YM, Nurmohamed MT. Effect of anti-inflammatory therapy on vascular biomarkers for subclinical cardiovascular disease in rheumatoid arthritis patients. Rheumatol Int. 2023;43:315–22.PubMedCrossRef
42.
Papamichail GV, Markatseli TE, Georgiadis AN, et al. The effects of biologic agents on cardiovascular risk factors and atherosclerosis in rheumatoid arthritis patients: a prospective observational study. Heart Vessels. 2022;37:2128–36.PubMedCrossRef
43.
Anghel D, Sirbu CA, Hoinoiu EM, et al. Influence of anti-TNF therapy and homocysteine level on carotid intima-media thickness in rheumatoid arthritis patients. Exp Ther Med. 2022;23:59.PubMedCrossRef
44.
van Sijl AM, van Eijk IC, Peters MJ, et al. Tumour necrosis factor blocking agents and progression of subclinical atherosclerosis in patients with ankylosing spondylitis. Ann Rheum Dis. 2015;74:119–23.PubMedCrossRef
45.
Ramonda R, Puato M, Punzi L, et al. Atherosclerosis progression in psoriatic arthritis patients despite the treatment with tumor necrosis factor-alpha blockers: a two-year prospective observational study. Joint Bone Spine. 2014;81:421–5.PubMedCrossRef
46.
Eder L, Joshi AA, Dey AK, et al. Association of tumor necrosis factor inhibitor treatment with reduced indices of subclinical atherosclerosis in patients with psoriatic disease. Arthritis Rheumatol. 2018;70:408–16.PubMedCrossRef
47.
Arida A, Protogerou AD, Konstantonis G, et al. Subclinical atherosclerosis is not accelerated in patients with ankylosing spondylitis with low disease activity: new data and metaanalysis of published studies. J Rheumatol. 2015;42:2098–105.PubMedCrossRef
48.
Abdulmajid B, Blanken AB, van Geel EH, Daams JG, Nurmohamed MT. Effect of TNF inhibitors on arterial stiffness and intima media thickness in rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol. 2023;42:999–1011.PubMedPubMedCentralCrossRef
49.
Tam LS, Kitas GD, González-Gay MA. Can suppression of inflammation by anti-TNF prevent progression of subclinical atherosclerosis in inflammatory arthritis? Rheumatology (Oxford). 2014;53:1108–19.PubMedCrossRef
50.
Galarraga B, Khan F, Kumar P, Pullar T, Belch JJ. Etanercept improves inflammation-associated arterial stiffness in rheumatoid arthritis. Rheumatology (Oxford). 2009;48:1418–23.PubMedCrossRef
51.
Mathieu S, Pereira B, Couderc M, Rabois E, Dubost JJ, Soubrier M. No significant changes in arterial stiffness in patients with ankylosing spondylitis after tumour necrosis factor alpha blockade treatment for 6 and 12 months. Rheumatology (Oxford). 2013;52:204–9.PubMedCrossRef
52.
Angel K, Provan SA, Gulseth HL, Mowinckel P, Kvien TK, Atar D. Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study. Hypertension. 2010;55:333–8.PubMedCrossRef
53.
Giollo A, Cioffi G, Ognibeni F, et al. Tumour necrosis factor inhibitors reduce aortic stiffness progression in patients with long-standing rheumatoid arthritis. Arthritis Res Ther. 2021;23:158.PubMedPubMedCentralCrossRef
54.
Blanken AB, Agca R, van Sijl AM, et al. Arterial wall inflammation in rheumatoid arthritis is reduced by anti-inflammatory treatment. Semin Arthritis Rheum. 2021;51:457–63.PubMedCrossRef
55.
Solomon DH, Giles JT, Liao KP, et al. Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2023;82:324–30.PubMedCrossRef
56.
Charles-Schoeman C, Buch MH, Dougados M, et al. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL Surveillance. Ann Rheum Dis. 2023;82:119–29.PubMedCrossRef
57.
Fleischmann R, Mysler E, Bessette L, et al. Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study. RMD Open. 2022;8: e002012.PubMedPubMedCentralCrossRef
58.
Fleischmann R, Pangan AL, Song IH, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double-blind, randomized controlled trial. Arthritis Rheumatol. 2019;71:1788–800.PubMedCrossRef
59.
Giles JT, Sattar N, Gabriel S, et al. Cardiovascular safety of tocilizumab versus etanercept in rheumatoid arthritis: a randomized controlled trial. Arthritis Rheumatol. 2020;72:31–40.PubMedCrossRef
60.
Jobanputra P, Maggs F, Deeming A, et al. A randomised efficacy and discontinuation study of etanercept versus adalimumab (RED SEA) for rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study of first TNF inhibitor use: outcomes over 2 years. BMJ Open. 2012;2: e001395.PubMedPubMedCentralCrossRef
61.
Karpouzas GA, Szekanecz Z, Baecklund E, et al. Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a post hoc analysis of ORAL Surveillance. Ther Adv Musculoskelet Dis. 2023;15:1759720X231201047.PubMedPubMedCentralCrossRef
62.
Kristensen LE, Danese S, Yndestad A, et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023;82:901–10.PubMedCrossRef
63.
Miller H, Wallman JK, Petersson IF, et al. Mortality over 14 years in MTX-refractory patients randomized to a strategy of addition of infliximab or sulfasalazine and hydroxychloroquine. Rheumatology (Oxford). 2021;60:2217–22.PubMedCrossRef
64.
Smolen JS, Burmester GR, Combe B, et al. Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study. Lancet. 2016;388:2763–74.PubMedCrossRef
65.
McInnes IB, Behrens F, Mease PJ, et al. Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial. Lancet. 2020;395:1496–505.PubMedCrossRef
66.
McInnes IB, Kato K, Magrey M, et al. Efficacy and safety of upadacitinib in patients with psoriatic arthritis: 2-year results from the phase 3 SELECT-PsA 1 study. Rheumatol Ther. 2023;10:275–92.PubMed
67.
Buch MH, Charles-Schoeman C, Curtis J, et al. POS0237 Major adverse cardiovascular events, malignancies and venous thromboembolism by baseline cardiovascular risk: a post hoc analysis of ORAL Surveillance. Ann Rheum Dis. 2022;81:356–7.CrossRef
68.
Charles-Schoeman C, Buch MH, Dougados M, et al. Risk factors for major adverse cardiovascular events in patients aged ≥50 years with rheumatoid arthritis and ≥1 additional cardiovascular risk factor: a post hoc analysis of ORAL Surveillance [abstract]. Ann Rheum Dis. 2022;81:611–2.CrossRef
69.
Szekanecz Z, Giles JT, Buch MH, et al. POS0110 Incidence of major adverse cardiovascular events stratified by geographic region and baseline cardiovascular risk: a post hoc analysis of ORAL Surveillance. Ann Rheum Dis. 2022;81:278–9.CrossRef
70.
Burmester GR, Mease P, Dijkmans BA, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. 2009;68:1863–9.PubMedCrossRef
71.
Weinblatt ME, Bathon JM, Kremer JM, et al. Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011;63:373–82.PubMedCrossRef
72.
Wasko MC, Hsia EC, Kirkham B, et al. Effect of golimumab on carotid atherosclerotic disease measures and cardiovascular events in inflammatory arthritides. J Clin Rheumatol. 2014;20:1–10.PubMedCrossRef
73.
Bykerk VP, Cush J, Winthrop K, et al. Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials. Ann Rheum Dis. 2015;74:96–103.PubMedCrossRef
74.
Kay J, Fleischmann R, Keystone E, et al. Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Ann Rheum Dis. 2015;74:538–46.PubMedCrossRef
75.
Kay J, Fleischmann R, Keystone E, et al. Five-year safety data from 5 clinical trials of subcutaneous golimumab in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2016;43:2120–30.PubMedCrossRef
76.
Yang ZS, Lin NN, Li L, Li Y. The effect of TNF inhibitors on cardiovascular events in psoriasis and psoriatic arthritis: an updated meta-analysis. Clin Rev Allergy Immunol. 2016;51:240–7.PubMedCrossRef
77.
Champs B, Degboé Y, Barnetche T, Cantagrel A, Ruyssen-Witrand A, Constantin A. Short-term risk of major adverse cardiovascular events or congestive heart failure in patients with psoriatic arthritis or psoriasis initiating a biological therapy: a meta-analysis of randomised controlled trials. RMD Open. 2019;5: e000763.PubMedPubMedCentralCrossRef
78.
Curtis JR, Mariette X, Gaujoux-Viala C, et al. Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis and Crohn’s disease: a pooled analysis of 11 317 patients across clinical trials. RMD Open. 2019;5: e000942.PubMedPubMedCentralCrossRef
79.
Burmester GR, Gordon KB, Rosenbaum JT, et al. Long-term safety of adalimumab in 29,967 adult patients from global clinical trials across multiple indications: an updated analysis. Adv Ther. 2020;37:364–80.PubMedCrossRef
80.
Thanigaimani S, Phie J, Krishna SM, Moxon J, Golledge J. Effect of disease modifying anti-rheumatic drugs on major cardiovascular events: a meta-analysis of randomized controlled trials. Sci Rep. 2021;11:6627.PubMedPubMedCentralCrossRef
81.
Husni ME, Deodhar A, Schwartzman S, et al. Pooled safety results across phase 3 randomized trials of intravenous golimumab in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Arthritis Res Ther. 2022;24:73.PubMedPubMedCentralCrossRef
82.
Brigante A, Quintana R, Isnardi C, et al. Cardiovascular and oncologic outcomes of anti-TNF alfa and JAK inhibitors in patients with rheumatoid and psoriatic arthritis. Real world data and insights of BIOBADASAR 3.0 Registry [abstract]. Arthritis Rheumatol. 2022;74:722.
83.
Chicre D, Pugliesi A, Barros Bértolo M, de Abreu Souza Filho VF, Carvalho L. Compared mortality and cardiovascular safety of JAK inhibitors and tocilizumab in patients with RA : a systematic review and network meta-analysis [abstract]. Arthritis Rheumatol. 2022;74:284.
84.
Liew J, Treu T, Park Y, et al. The association of early TNF inhibitor use with incident cardiovascular events in ankylosing spondylitis [abstract]. Arthritis Rheumatol. 2022;74:415.
85.
Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Anti-TNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133–40.PubMedCrossRef
86.
Westlake SL, Colebatch AN, Baird J, et al. Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford). 2011;50:518–31.PubMedCrossRef
87.
Ljung L, Simard JF, Jacobsson L, Rantapää-Dahlqvist S, Askling J, Anti-Rheumatic Therapy in Sweden (ARTIS) Study Group. Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis. Arthritis Rheum. 2012;64:42–52.
88.
Low AS, Lunt M, Mercer LK, et al. Association between ischemic stroke and tumor necrosis factor inhibitor therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1337–45.PubMedPubMedCentralCrossRef
89.
Meissner Y, Schafer M, Albrecht K, et al. Risk of major adverse cardiovascular events in patients with rheumatoid arthritis treated with conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs: observational data from the German RABBIT register. RMD Open. 2023;9.
90.
Lunt M, Watson KD, Dixon WG, et al. No evidence of association between anti-tumor necrosis factor treatment and mortality in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2010;62:3145–53.PubMedPubMedCentralCrossRef
91.
Lee JL, Sinnathurai P, Buchbinder R, Hill C, Lassere M, March L. Biologics and cardiovascular events in inflammatory arthritis: a prospective national cohort study. Arthritis Res Ther. 2018;20:171.PubMedPubMedCentralCrossRef
92.
Low AS, Symmons DP, Lunt M, et al. Relationship between exposure to tumour necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76:654–60.PubMedCrossRef
93.
Morgan CL, Emery P, Porter D, et al. Treatment of rheumatoid arthritis with etanercept with reference to disease-modifying anti-rheumatic drugs: long-term safety and survival using prospective, observational data. Rheumatology (Oxford). 2014;53:186–94.PubMedCrossRef
94.
Nurmohamed M, Bao Y, Signorovitch J, Trahey A, Mulani P, Furst DE. Longer durations of antitumour necrosis factor treatment are associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis. RMD Open. 2015;1: e000080.PubMedPubMedCentralCrossRef
95.
Chen HK, Shao SC, Weng MY, et al. Risk of heart failure in rheumatoid arthritis patients treated with tumor necrosis factor-alpha inhibitors. Clin Pharmacol Ther. 2021;110:1595–603.PubMedCrossRef
96.
Chen YJ, Liu SC, Lai KL, et al. Factors associated with risk of major adverse cardiovascular events in patients with rheumatoid arthritis: a nationwide, population-based, case-control study. Ther Adv Musculoskelet Dis. 2021;13:1759720X211030809.
97.
Delcoigne B, Ljung L, Provan SA, et al. Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries. Ann Rheum Dis. 2022;81:789–97.PubMedCrossRef
98.
Frisell T, Bower H, Morin M, et al. Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme. Ann Rheum Dis. 2023;82:601–10.PubMedCrossRef
99.
Min HK, Kim H, Jeong HJ, et al. Risk of cancer, cardiovascular disease, thromboembolism, and mortality in patients with rheumatoid arthritis receiving Janus kinase inhibitors: a real-world retrospective observational study using Korean health insurance data. Epidemiol Health. 2023;45: e2023045.PubMedPubMedCentralCrossRef
100.
Xie F, Yun H, Levitan EB, Muntner P, Curtis JR. Tocilizumab and the risk of cardiovascular disease: direct comparison among biologic disease-modifying antirheumatic drugs for rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2019;71:1004–18.PubMedCrossRef
101.
Arendse R, Rahman P, Baer P, et al. Long-term treatment with golimumab is a safe treatment option regardless of risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis: results from a real-world Canadian setting [abstract]. Arthritis Rheumatol. 2022;74:1423.
102.
Gottenberg JE, Kessouri M, Rudant J, Assi N, Grenier B. Acute cardiovascular events risk in rheumatoid arthritis patients treated with tofacitinib or TNF inhibitors, a nationwide cohort study: RELATION study [abstract]. Ann Rheum Dis. 2023;82:402.CrossRef
103.
Zhang J, Xie F, Yun H, et al. Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75:1813–8.PubMedCrossRef
104.
Tian Z, Kearlsey-Fleet L, Lauper K, et al. No difference in risk of myocardial infarction among patients receiving either IL6 or TNF inhibitors for rheumatoid arthritis [abstract OA01]. Rheumatology (Oxford). 2023;62.
105.
Sparks JA, Lesperance T, Accortt NA, Solomon DH. Subsequent cardiovascular events among patients with rheumatoid arthritis, psoriatic arthritis, or psoriasis: patterns of disease-modifying antirheumatic drug treatment. Arthritis Care Res (Hoboken). 2019;71:512–20.PubMedCrossRef
106.
Stovall R, Peloquin C, Felson D, Neogi T, Dubreuil M. Relation of therapies for ankylosing spondylitis and psoriatic arthritis to risk of myocardial infarction: a nested case control study. BMC Rheumatol. 2021;5:36.PubMedPubMedCentralCrossRef
107.
Wu JJ, Poon KY. Tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis, psoriatic arthritis, or both. J Drugs Dermatol. 2014;13:932–4.PubMed
108.
Wu JJ, Poon KY, Bebchuk JD. Association between the type and length of tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. J Drugs Dermatol. 2013;12:899–903.PubMed
109.
Vinker Shuster M, Gendelman O, Tiosano S, Comaneshter D, Cohen AD, Amital H. Ischemic heart disease and ankylosing spondylitis-assessing the role of inflammation. Clin Rheumatol. 2018;37:1053–8.PubMedCrossRef
110.
Kwon OC, Park MC. Effect of tumor necrosis factor inhibitors on risk of cardiovascular disease in patients with axial spondyloarthritis. Arthritis Res Ther. 2022;24:141.PubMedPubMedCentralCrossRef
111.
Chan SCW, Teo CK, Li PH, Lau KK, Lau CS, Chung HY. Cardiovascular risk in patients with spondyloarthritis and association with anti-TNF drugs. Ther Adv Musculoskelet Dis. 2021;13:1759720X211032444.
112.
Fakih O, Desmarets M, Martin B, et al. Impact of NSAIDs on 8-year cumulative incidence of major cardiovascular events in patients with ankylosing spondylitis: a nationwide study. Rheumatology (Oxford). 2023;62:3317–22.PubMedCrossRef
113.
Merjanah S, Driscoll D, Peloquin C, Liew J, Dubreuil M. Major adverse cardiovascular event and venous thromboembolism risk comparing advanced therapies among individuals with axial spondylarthritis and psoriatic arthritis [abstract]. Arthritis Rheumatol. 2023;75.
114.
van Halm VP, Peters MJ, Voskuyl AE, et al. Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRE Investigation. Ann Rheum Dis. 2009;68:1395–400.PubMedCrossRef
115.
Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76:17–28.PubMedCrossRef
116.
del Rincón I, Polak JF, O’Leary DH, et al. Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis. Ann Rheum Dis. 2015;74:1118–23.PubMedCrossRef
117.
Zhang J, Chen L, Delzell E, et al. The association between inflammatory markers, serum lipids and the risk of cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis. 2014;73:1301–8.PubMedCrossRef
118.
Gossec L, Kerschbaumer A, Ferreira RJO, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis. 2024;83:706–19.PubMedCrossRef
119.
Galajda NÁ, Meznerics FA, Mátrai P, et al. Reducing cardiovascular risk in immune-mediated inflammatory diseases: tumour necrosis factor inhibitors compared to conventional therapies-a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2024;38:1070–88.PubMedCrossRef
120.
Hoisnard L, Pina Vegas L, Dray-Spira R, Weill A, Zureik M, Sbidian E. Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study. Ann Rheum Dis. 2023;82:182–8.PubMedCrossRef
121.
Mok CC, So H, Yim CW, et al. Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry. Rheumatology (Oxford). 2024;63:358–65.PubMedCrossRef
122.
Daïen CI, Tubery A, Beurai-Weber M, et al. Relevance and feasibility of a systematic screening of multimorbidities in patients with chronic inflammatory rheumatic diseases. Joint Bone Spine. 2019;86:49–54.PubMedCrossRef
123.
Immediato Daien C, Georgescu V, Decarriere G, Mercier G, Morel J. Systematic screening for multimorbidities in patients with inflammatory rheumatic diseases enhanced preventive medication use and reduced hospitalisations: an exposed-non-exposed study. RMD Open. 2024;10.
124.
Emanuel G, Charlton J, Ashworth M, Gulliford MC, Dregan A. Cardiovascular risk assessment and treatment in chronic inflammatory disorders in primary care. Heart. 2016;102:1957–62.PubMedCrossRef
125.
126.
Murphy L, Saab MM, Cornally N, McHugh S, Cotter P. Cardiovascular disease risk assessment in patients with rheumatoid arthritis: a scoping review. Clin Rheumatol. 2024;43:2187–202.PubMedPubMedCentralCrossRef
127.
JBS3 Board. Joint British Societies' consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart. 2014;100:ii1–ii67.
128.
Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ. 2017;357: j2099.PubMedPubMedCentralCrossRef
129.
Liew JW, Jafarzadeh SR, Dubreuil M, et al. The association of tumor necrosis factor inhibitor use with incident hypertension in ankylosing spondylitis: data from the PSOAS cohort. J Rheumatol. 2022;49:274–80.PubMedCrossRef
130.
Desai RJ, Solomon DH, Schneeweiss S, Danaei G, Liao KP, Kim SC. Tumor necrosis factor-α inhibitor use and the risk of incident hypertension in patients with rheumatoid arthritis. Epidemiology. 2016;27:414–22.PubMedPubMedCentralCrossRef
131.
Kim SK, Kwak SG, Choe JY. Association between biologic disease modifying anti-rheumatic drugs and incident hypertension in patients with rheumatoid arthritis: results from prospective nationwide KOBIO Registry. Medicine (Baltimore). 2020;99: e19415.PubMedCrossRef
132.
Mebrahtu TF, Morgan AW, West RM, Stewart PM, Pujades-Rodriguez M. Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study. CMAJ. 2020;192:E295–301.PubMedPubMedCentralCrossRef
133.
Morrison A, Ramey DR, van Adelsberg J, Watson DJ. Systematic review of trials of the effect of continued use of oral non-selective NSAIDs on blood pressure and hypertension. Curr Med Res Opin. 2007;23:2395–404.PubMedCrossRef
134.
Ishiguro C, Fujita T, Omori T, Fujii Y, Mayama T, Sato T. Assessing the effects of non-steroidal anti-inflammatory drugs on antihypertensive drug therapy using post-marketing surveillance database. J Epidemiol. 2008;18:119–24.PubMedPubMedCentralCrossRef
135.
Luo Y, Ren X, Weng S, Yan C, Mao Q, Peng D. Improvements in high-density lipoprotein quantity and quality contribute to the cardiovascular benefits by anti-tumor necrosis factor therapies in rheumatoid arthritis: a systemic review and meta-analysis. Front Cardiovasc Med. 2021;8: 765749.PubMedPubMedCentralCrossRef
136.
Charles-Schoeman C, Gugiu GB, Ge H, et al. Remodeling of the HDL proteome with treatment response to abatacept or adalimumab in the AMPLE trial of patients with rheumatoid arthritis. Atherosclerosis. 2018;275:107–14.PubMedPubMedCentralCrossRef
137.
Calvo Alén J, Lavin-Gomez BA, Aurrecoechea E, Guerra Ruiz AR, Martínez Taboada V, Gómez GJ. TNF inhibitors exert a “hidden” beneficial effect in the cardiovascular lipoprotein profile of RA patients. Biologics. 2022;16:187–97.PubMedPubMedCentral
138.
Kawashiri SY, Kawakami A, Yamasaki S, et al. Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis. Rheumatol Int. 2011;31:451–6.PubMedCrossRef
139.
Li N, Gou ZP, Du SQ, et al. Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis. Clin Rheumatol. 2022;41:677–88.PubMedCrossRef
140.
Avouac J, Elhai M, Forien M, et al. Influence of inflammatory and non-inflammatory rheumatic disorders on the clinical and biological profile of type-2 diabetes. Rheumatology (Oxford). 2021;60:3598–606.PubMedCrossRef
141.
Wang CR, Tsai HW. Anti- and non-tumor necrosis factor-alpha-targeted therapies effects on insulin resistance in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. World J Diabetes. 2021;12:238–60.PubMedPubMedCentralCrossRef
142.
Burska AN, Sakthiswary R, Sattar N. Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis: a systematic review and meta-analysis. PLoS ONE. 2015;10: e0128889.PubMedPubMedCentralCrossRef
143.
van den Oever IAM, Baniaamam M, Simsek S, et al. The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis. Rheumatol Int. 2021;41:319–28.PubMedCrossRef
144.
Otsuka Y, Kiyohara C, Kashiwado Y, et al. Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study. PLoS ONE. 2018;13: e0196368.PubMedPubMedCentralCrossRef
145.
Steen DL, Khan I, Andrade K, Koumas A, Giugliano RP. Event rates and risk factors for recurrent cardiovascular events and mortality in a contemporary post acute coronary syndrome population representing 239 234 patients during 2005 to 2018 in the United States. J Am Heart Assoc. 2022;11: e022198.PubMedPubMedCentralCrossRef
Metadata
Title
The Cardiovascular Safety of Tumour Necrosis Factor Inhibitors in Arthritic Conditions: A Structured Review with Recommendations
Authors
Jérôme Avouac
Hafid Ait-Oufella
Caroline Habauzit
Salim Benkhalifa
Bernard Combe
Publication date
28-02-2025
Publisher
Springer Healthcare
Published in
Rheumatology and Therapy / Issue 2/2025
Print ISSN: 2198-6576
Electronic ISSN: 2198-6584
DOI
https://doi.org/10.1007/s40744-025-00753-x

Other articles of this Issue 2/2025

Effective Second-Line b/tsDMARDs for Patients with Rheumatoid Arthritis Unresponsive to First-Line b/tsDMARDs from the FIRST Registry

Letter to the Editor Regarding “Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: A Post Hoc Analysis of ORAL Surveillance”

Factors Influencing Treatment Satisfaction and Recognition Gaps Between Physicians and Patients with Systemic Sclerosis

Letter to the Editor Regarding: “Incidence of Malignancies and the Association with Biological Disease-Modifying Antirheumatic Drugs in Japanese Patients with Rheumatoid Arthritis: A Time-Dependent Analysis from the IORRA Patient Registry”

Association Between Diagnostic Delay and Economic and Clinical Burden in Axial Spondyloarthritis: A Multicentre Retrospective Observational Study

Effect of Ozoralizumab Administration with or without Methotrexate in Patients with Rheumatoid Arthritis: A Post-Hoc Analysis

Keynote webinar | Spotlight on advances in lupus

  • Live
  • Webinar | 27-05-2025 | 18:00 (CEST)

Systemic lupus erythematosus is a severe autoimmune disease that can cause damage to almost every system of the body. Join this session to learn more about novel biomarkers for diagnosis and monitoring and familiarise yourself with current and emerging targeted therapies.

Join us live: Tuesday 27th May, 18:00-19:15 (CEST)

Prof. Edward Vital
Prof. Ronald F. van Vollenhoven
Developed by: Springer Medicine
Register now
Webinar

Elevate your expertise in aplastic anemia (Link opens in a new window)

Transform the way you care for your patients with aplastic anemia with our 3-module series using real-world case studies and expert insights. Discover why early diagnosis matters, explore the benefits and risks of current treatments, and develop tailored approaches for complex cases. 

Supported by:
  • Pfizer
Developed by: Springer Healthcare IME
Learn more
Image Credits