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Review Article| Volume 49, ISSUE 1, P165-178, February 2023

Evidence for Biologic Drug Modifying Anti-Rheumatoid Drugs and Association with Cardiovascular Disease Risk Mitigation in Inflammatory Arthritis

  • Brittany Weber
    Correspondence
    Corresponding author. Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115.
    Affiliations
    Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA

    Cardiovascular Imaging Program, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
    Search for articles by this author
  • Katherine P. Liao
    Affiliations
    Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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      Keywords

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      References

        • Agca R.
        • Heslinga S.C.
        • van Halm V.P.
        • et al.
        Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders.
        Heart. 2016; 102: 790-795
        • Gelfand J.M.
        • Troxel A.B.
        • Lewis J.D.
        • et al.
        The risk of mortality in patients with psoriasis: results from a population-based study.
        Arch Dermatol. 2007; 143: 1493-1499
        • Urowitz M.B.
        • Gladman D.
        • Ibañez D.
        • et al.
        Atherosclerotic vascular events in a multinational inception cohort of systemic lupus erythematosus.
        Arthritis Care Res (Hoboken). 2010; 62: 881-887
        • Avina-Zubieta J.A.
        • Thomas J.
        • Sadatsafavi M.
        • et al.
        Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies.
        Ann Rheum Dis. 2012; 71: 1524-1529
        • England B.R.
        • Thiele G.M.
        • Anderson D.R.
        • et al.
        Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications.
        BMJ. 2018; 361: k1036
        • Liew J.W.
        • Ramiro S.
        • Gensler L.S.
        Cardiovascular morbidity and mortality in ankylosing spondylitis and psoriatic arthritis.
        Best Pract Res Clin Rheumatol. 2018; 32: 369-389
        • Teague H.
        • Mehta N.N.
        The link between inflammatory disorders and coronary heart disease: a look at recent studies and novel drugs in development.
        Curr Atheroscler Rep. 2016; 18: 3
        • Weber B.
        • Liao K.P.
        • DiCarli M.
        • et al.
        Cardiovascular disease prevention in individuals with underlying chronic inflammatory disease.
        Curr Opin Cardiol. 2021; 36: 549-555
        • Davignon J.
        • Ganz P.
        Role of endothelial dysfunction in atherosclerosis.
        Circulation. 2004; 109: III-III27
        • Cahill P.A.
        • Redmond E.M.
        Vascular endothelium – Gatekeeper of vessel health.
        Atherosclerosis. 2016; 248: 97-109
        • Boulanger C.M.
        Endothelium.
        Arterioscler Thromb Vasc Biol. 2016; 36: e26-e31
        • Hansson G.K.
        • Robertson A.-K.L.
        • Söderberg-Nauclér C.
        Inflammation and atherosclerosis.
        Annu Rev Pathol. 2006; 1: 297-329
        • Libby P.
        Inflammation in atherosclerosis.
        Arterioscler Thromb Vasc Biol. 2012; 32: 2045-2051
        • Libby P.
        • Buring J.E.
        • Badimon L.
        • et al.
        Atherosclerosis.
        Nat Rev Dis Primers. 2019; 5: 56
        • Abuabara K.
        • Azfar R.S.
        • Shin D.B.
        • et al.
        Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the United Kingdom.
        Br J Dermatol. 2010; 163: 586-592
        • Kaye J.A.
        • Li L.
        • Jick S.S.
        Incidence of risk factors for myocardial infarction and other vascular diseases in patients with psoriasis.
        Br J Dermatol. 2008; 159: 895-902
        • Shah K.
        • Mellars L.
        • Changolkar A.
        • et al.
        Real-world burden of comorbidities in US patients with psoriasis.
        J Am Acad Dermatol. 2017; 77: 287-292.e4
        • Sommer D.M.
        • Jenisch S.
        • Suchan M.
        • et al.
        Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis.
        Arch Dermatol Res. 2006; 298: 321-328
        • Raychaudhuri S.K.
        • Chatterjee S.
        • Nguyen C.
        • et al.
        Increased Prevalence of the Metabolic Syndrome in Patients with Psoriatic Arthritis.
        Metab Syndr Relat Disord. 2010; 8: 331-334
        • Azfar R.S.
        • Seminara N.M.
        • Shin D.B.
        • et al.
        Increased risk of diabetes mellitus and likelihood of receiving diabetes mellitus treatment in patients with psoriasis.
        Arch Dermatol. 2012; 148: 995-1000
        • Kimhi O.
        • Caspi D.
        • Bornstein N.M.
        • et al.
        Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis.
        Semin Arthritis Rheum. 2007; 36: 203-209
        • del Rincón I.
        • Polak J.F.
        • O’Leary D.H.
        • et al.
        Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis.
        Ann Rheum Dis. 2015; 74: 1118-1123
        • Navarro-Millán I.
        • Yang S.
        • DuVall S.L.
        • et al.
        Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration.
        Ann Rheum Dis. 2016; 75: 341-347
        • Solomon D.H.
        • Kremer J.
        • Curtis J.R.
        • et al.
        Explaining the cardiovascular risk associated with rheumatoid arthritis: traditional risk factors versus markers of rheumatoid arthritis severity.
        Ann Rheum Dis. 2010; 69: 1920-1925
        • Liao K.P.
        • Liu J.
        • Lu B.
        • et al.
        Association between lipid levels and major adverse cardiovascular events in rheumatoid arthritis compared to non–rheumatoid arthritis patients.
        Arthritis Rheum. 2015; 67: 2004-2010
        • Yiu Z.Z.N.
        • Exton L.S.
        • Jabbar-Lopez Z.
        • et al.
        Risk of serious infections in patients with psoriasis on biologic therapies: a systematic review and meta-analysis.
        J Invest Dermatol. 2016; 136: 1584-1591
        • Jani M.
        • Barton A.
        • Hyrich K.
        Prediction of infection risk in rheumatoid arthritis patients treated with biologics: are we any closer to risk stratification?.
        Curr Opin Rheumatol. 2019; 31: 285-292
        • Barnabe C.
        • Martin B.-J.
        • Ghali W.A.
        Systematic review and meta-analysis: anti-tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis.
        Arthritis Care Res (Hoboken). 2011; 63: 522-529
        • Low A.S.L.
        • Symmons D.P.M.
        • 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: 654-660
        • Jacobsson L.T.H.
        • Turesson C.
        • Nilsson J.-A.
        • et al.
        Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis.
        Ann Rheum Dis. 2007; 66: 670-675
        • Low A.S.L.
        • Lunt M.
        • Mercer L.K.
        • et al.
        Association between ischemic stroke and tumor necrosis factor inhibitor therapy in patients with rheumatoid arthritis.
        Arthritis Rheum. 2016; 68: 1337-1345
        • Naranjo A.
        • Sokka T.
        • Descalzo M.A.
        • et al.
        Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study.
        Arthritis Res Ther. 2008; 10: R30
        • Lee J.L.
        • Sinnathurai P.
        • Buchbinder R.
        • et al.
        Biologics and cardiovascular events in inflammatory arthritis: a prospective national cohort study.
        Arthritis Res Ther. 2018; 20: 171
        • Hürlimann D.
        • Forster A.
        • Noll G.
        • et al.
        Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.
        Circulation. 2002; 106: 2184-2187
        • Syngle A.
        • Vohra K.
        • Sharma A.
        • et al.
        Endothelial dysfunction in ankylosing spondylitis improves after tumor necrosis factor-alpha blockade.
        Clin Rheumatol. 2010; 29: 763-770
        • Capkin E.
        • Karkucak M.
        • Kiris A.
        • et al.
        Anti-TNF-α therapy may not improve arterial stiffness in patients with AS: a 24-week follow-up.
        Rheumatology (Oxford). 2012; 51: 910-914
        • Mathieu S.
        • Pereira B.
        • Couderc M.
        • et al.
        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: 204-209
        • Di Minno M.N.D.
        • Iervolino S.
        • Peluso R.
        • et al.
        • CaRRDs study group
        Carotid intima-media thickness in psoriatic arthritis: differences between tumor necrosis factor-α blockers and traditional disease-modifying antirheumatic drugs.
        Arterioscler Thromb Vasc Biol. 2011; 31: 705-712
        • Karpouzas G.A.
        • Ormseth S.R.
        • Hernandez E.
        • et al.
        Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High-Risk Lesions.
        Arthritis Rheum. 2020; 72: 1467-1475
        • Elmets C.A.
        • Leonardi C.L.
        • Davis D.M.R.
        • et al.
        Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.
        J Am Acad Dermatol. 2019; 80: 1073-1113
        • Ridker P.M.
        • Everett B.M.
        • Thuren T.
        • et al.
        Antiinflammatory therapy with canakinumab for atherosclerotic disease.
        N Engl J Med. 2017; 377: 1119-1131
        • Ridker P.M.
        From CRP to IL-6 to IL-1: moving upstream to identify novel targets for atheroprotection.
        Circ Res. 2016; 118: 145-156
        • Ridker P.M.
        • Rane M.
        Interleukin-6 signaling and anti-interleukin-6 therapeutics in cardiovascular disease.
        Circ Res. 2021; 128: 1728-1746
        • Ridker P.M.
        • MacFadyen J.G.
        • Glynn R.J.
        • et al.
        Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial. Eur Heart J.
        (Available at:) (Accessed April 6, 2020)
        • Lindmark E.
        • Diderholm E.
        • Wallentin L.
        • et al.
        Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy.
        JAMA. 2001; 286: 2107-2113
        • Lamb Y.N.
        • Deeks E.D.
        Sarilumab: A Review in Moderate to Severe Rheumatoid Arthritis.
        Drugs. 2018; 78: 929-940
        • Smolen J.S.
        • Landewé R.B.M.
        • Bijlsma J.W.J.
        • et al.
        EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update.
        Ann Rheum Dis. 2020; 79: 685-699
        • Cacciapaglia F.
        • Anelli M.G.
        • Rinaldi A.
        • et al.
        Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment.
        Mediators Inflamm. 2018; 2018: 2453265
        • Jones G.
        • Sebba A.
        • Gu J.
        • et al.
        Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study.
        Ann Rheum Dis. 2010; 69: 88-96
        • Robertson J.
        • Porter D.
        • Sattar N.
        • et al.
        Interleukin-6 blockade raises LDL via reduced catabolism rather than via increased synthesis: a cytokine-specific mechanism for cholesterol changes in rheumatoid arthritis.
        Ann Rheum Dis. 2017; 76: 1949-1952
        • Singh S.
        • Fumery M.
        • Singh A.G.
        • et al.
        Comparative Risk of Cardiovascular Events With Biologic and Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.
        Arthritis Care Res. 2020; 72: 561-576
        • Ridker P.M.
        • Libby P.
        • MacFadyen J.G.
        • et al.
        Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS).
        Eur Heart J. 2018; 39: 3499-3507
        • Ridker P.M.
        • Devalaraja M.
        • Baeres F.M.M.
        • et al.
        IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial.
        The Lancet. 2021; 397: 2060-2069
        • Ridker P.M.
        From RESCUE to ZEUS: will interleukin-6 inhibition with ziltivekimab prove effective for cardiovascular event reduction?.
        Cardiovasc Res. 2021; 117: e138-e140
        • Charles-Schoeman C.
        • Gugiu G.B.
        • 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: 107-114
        • 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: 1813-1818
        • Gonzalez-Juanatey C.
        • Vazquez-Rodriguez T.R.
        • Miranda-Filloy J.A.
        • et al.
        The high prevalence of subclinical atherosclerosis in patients with ankylosing spondylitis without clinically evident cardiovascular disease.
        Medicine (Baltimore). 2009; 88: 358-365
        • Kyaw T.
        • Tipping P.
        • Bobik A.
        • et al.
        Opposing roles of B lymphocyte subsets in atherosclerosis.
        Autoimmunity. 2017; 50: 52-56
        • Stritesky G.L.
        • Yeh N.
        • Kaplan M.H.
        IL-23 promotes maintenance but not commitment to the Th17 lineage.
        J Immunol. 2008; 181: 5948-5955
        • Gelfand J.M.
        • Shin D.B.
        • Alavi A.
        • et al.
        A Phase IV, Randomized, double-blind, placebo-controlled crossover study of the effects of ustekinumab on vascular inflammation in psoriasis (the VIP-U Trial).
        J Invest Dermatol. 2020; 140: 85-93.e2
        • Gelfand J.M.
        • Shin D.B.
        • Duffin K.C.
        • et al.
        A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S).
        J Invest Dermatol. 2020; 140: 1784-1793.e2
        • Ignatios I.
        • Evangelia P.
        • George M.
        • et al.
        Lowering interleukin-12 activity improves myocardial and vascular function compared with tumor necrosis factor-a antagonism or cyclosporine in psoriasis.
        Circ Cardiovasc Imaging. 2017; 10: e006283
        • Gordon K.B.
        • Langley R.G.
        • Gottlieb A.B.
        • et al.
        A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis.
        J Invest Dermatol. 2012; 132: 304-314
        • Tzellos T.
        • Kyrgidis A.
        • Trigoni A.
        • et al.
        Association of ustekinumab and briakinumab with major adverse cardiovascular events.
        Dermatoendocrinol. 2012; 4: 320-323
        • Reich K.
        • Langley R.G.
        • Lebwohl M.
        • et al.
        Cardiovascular safety of ustekinumab in patients with moderate to severe psoriasis: results of integrated analyses of data from phase II and III clinical studies.
        Br J Dermatol. 2011; 164: 862-872
        • Reich K.
        • Papp K.A.
        • Griffiths C.E.M.
        • et al.
        An update on the long-term safety experience of ustekinumab: results from the psoriasis clinical development program with up to four years of follow-up.
        J Drugs Dermatol. 2012; 11: 300-312
        • Pina Vegas L.
        • Le Corvoisier P.
        • Penso L.
        • et al.
        Risk of major adverse cardiovascular events in patients initiating biologics/apremilast for psoriatic arthritis: a nationwide cohort study. Rheumatology.
        (Available at:) (Accessed July 22, 2021)
        • Ryan C.
        • Leonardi C.L.
        • Krueger J.G.
        • et al.
        Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials.
        JAMA. 2011; 306: 864-871
        • Tzellos T.
        • Kyrgidis A.
        • Zouboulis C.C.
        Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta-analysis of randomized controlled trials.
        J Eur Acad Dermatol Venereol. 2013; 27: 622-627
        • Erbel C.
        • Akhavanpoor M.
        • Okuyucu D.
        • et al.
        IL-17A influences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis.
        J Immunol. 2014; 193: 4344-4355
        • Karbach S.
        • Croxford A.L.
        • Oelze M.
        • et al.
        Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease.
        Arterioscler Thromb Vasc Biol. 2014; 34: 2658-2668
        • Butcher M.J.
        • Gjurich B.N.
        • Phillips T.
        • et al.
        The IL-17A/IL-17RA axis plays a pro-atherogenic role via the regulation of aortic myeloid cell recruitment.
        Circ Res. 2012; 110: 675-687
        • Taleb S.
        • Tedgui A.
        • Mallat Z.
        IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles.
        Arterioscler Thromb Vasc Biol. 2015; 35: 258-264
        • Gagliani N.
        • Amezcua Vesely M.C.
        • Iseppon A.
        • et al.
        Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation.
        Nature. 2015; 523: 221-225
        • Brauner S.
        • Jiang X.
        • Thorlacius G.E.
        • et al.
        Augmented Th17 differentiation in Trim21 deficiency promotes a stable phenotype of atherosclerotic plaques with high collagen content.
        Cardiovasc Res. 2018; 114: 158-167
        • Lockshin B.
        • Balagula Y.
        • Merola J.F.
        Interleukin 17, inflammation, and cardiovascular risk in patients with psoriasis.
        J Am Acad Dermatol. 2018; 79: 345-352
        • Gao W.
        • McGarry T.
        • Orr C.
        • et al.
        Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors.
        Ann Rheum Dis. 2016; 75: 311-315
        • D’Urso D.F.
        • Chiricozzi A.
        • Pirro F.
        • et al.
        New JAK inhibitors for the treatment of psoriasis and psoriatic arthritis.
        G Ital Dermatol Venereol. 2020; 155: 411-420
        • Charles-Schoeman C.
        • Wicker P.
        • Gonzalez-Gay M.A.
        • et al.
        Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor.
        Semin Arthritis Rheum. 2016; 46: 261-271
        • Yoo B.W.
        Embarking on a Career in Cardio-Rheumatology.
        J Am Coll Cardiol. 2020; 75: 1488-1492
        • Anon A.
        Collaborative cardio-rheumatology clinic for primary prevention of cardiovascular diseases - a descriptive study. ACR Meeting Abstracts.
        (Available at:) (Accessed February 17, 2021)
        • Xie W.
        • Huang Y.
        • Xiao S.
        • et al.
        Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials.
        Meta-Analysis Ann Rheum Dis. 2019; 78: 1048-1054
        • Ytterberg S.R.
        • Bhatt D.L.
        • Mikuls T.R.
        • et al.
        Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis.
        Randomized Controlled Trial N Engl J Med. 2022; 386: 316-326
        • Maqsood M.H.
        • Weber B.N.
        • Haberman R.H.
        • et al.
        Cardiovascular and Venous Thromboembolic Risk With Janus Kinase Inhibitors in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis of Randomized Trials.
        ACR Open Rheumatology. 2022; https://doi.org/10.1002/acr2.11479
        • Khosrow-Khavar F.
        • Kim S.C.
        • Lee H.
        • et al.
        Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study.
        Ann Rheum Dis. 2022; 81: 798-804