Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study

AIMS The use of biologic therapy has increased over the past decade well beyond primary autoimmune diseases. Indeed, a recent trial using an anti-IL-1beta antibody reduced second myocardial infarction (MI) in those who have had MI. Psoriasis is a chronic inflammatory disease often treated with biologics when severe, is associated with increased risk of MI, in part driven by high-risk coronary plaque phenotypes by coronary computed tomography angiography (CCTA). We hypothesized that we would observe a reduction in inflammatory-driven phenotypes of coronary plaque, including non-calcified coronary plaque burden and lipid-rich necrotic core in those treated with biologic therapy after one-year compared with non-biologic therapy. METHODS AND RESULTS In a prospective, observational study, 290 participants were recruited from 1 January 2013 through 31 October 2018 with 215 completing one-year follow-up. Of the 238, 121 consecutive participants who were biologic treatment naïve at baseline were included. A blinded reader (blinded to patient demographics, visit and treatment) quantified total coronary plaque burden and plaque subcomponents (calcified and non-calcified) in the three main coronary vessels >2 mm using dedicated software (QAngio, Medis, Netherlands). Psoriasis patients were middle-aged [mean (standard deviation) age, 50.5 (12.1) years], mostly male (n = 70, 58%) with low cardiovascular risk by Framingham score [median (interquartile range, IQR), 3 (1-6)] and had moderate to severe skin disease at baseline [median (IQR) Psoriasis Area Severity Index, PASI, 8.6 (5.3-14.0)]. Biologic therapy was associated with a 6% reduction in non-calcified plaque burden (P = 0.005) reduction in necrotic core (P = 0.03), with no effect on fibrous burden (P = 0.71). Decrease in non-calcified plaque burden in the biologic treated group was significant compared with slow plaque progression in non-biologic treated (Δ, -0.07 mm2 vs. 0.06 mm2; P = 0.02) and associated with biologic treatment beyond adjustment for traditional cardiovascular risk factors (β = 0.20, P = 0.02). CONCLUSION In this observational study, we demonstrate that biologic therapy in severe psoriasis was associated with favourable modulation of coronary plaque indices by CCTA. These findings highlight the importance of systemic inflammation in coronary artery disease and support the conduct of larger, randomized trials.

[1]  A. Waisman,et al.  Antagonization of IL-17A Attenuates Skin Inflammation and Vascular Dysfunction in Mouse Models of Psoriasis. , 2019, The Journal of investigative dermatology.

[2]  M. Swartz,et al.  Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis. , 2019, Cell metabolism.

[3]  A. Armstrong,et al.  Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial , 2018, Circulation. Cardiovascular imaging.

[4]  A. Waisman,et al.  Aggravated Atherosclerosis and Vascular Inflammation With Reduced Kidney Function Depend on Interleukin-17 Receptor A and Are Normalized by Inhibition of Interleukin-17A , 2018, JACC. Basic to translational science.

[5]  Jonathan H. Chung,et al.  Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography , 2017, JAMA cardiology.

[6]  R. Harrington Targeting Inflammation in Coronary Artery Disease. , 2017, The New England journal of medicine.

[7]  P. Libby,et al.  Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease , 2017, The New England journal of medicine.

[8]  Jonathan H. Chung,et al.  Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study , 2017, Circulation.

[9]  N. Mehta,et al.  Psoriasis as a human model of disease to study inflammatory atherogenesis. , 2017, American journal of physiology. Heart and circulatory physiology.

[10]  M. Reilly,et al.  Comparison of Coronary Artery Calcium Scores Between Patients With Psoriasis and Type 2 Diabetes. , 2016, JAMA dermatology.

[11]  D. Bluemke,et al.  Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis. , 2015, European heart journal.

[12]  L. Shaw,et al.  Plaque Characterization by Coronary Computed Tomography Angiography and the Likelihood of Acute Coronary Events in Mid-Term Follow-Up. , 2015, Journal of the American College of Cardiology.

[13]  D. Bluemke,et al.  Noninvasive Imaging of Atherosclerotic Plaque Progression: Status of Coronary Computed Tomography Angiography. , 2015, Circulation. Cardiovascular imaging.

[14]  Michael T. Lu,et al.  Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. , 2015, The lancet. HIV.

[15]  D. Dey,et al.  Comparison of quantitative atherosclerotic plaque burden from coronary CT angiography in patients with first acute coronary syndrome and stable coronary artery disease. , 2014, Journal of cardiovascular computed tomography.

[16]  H. May,et al.  Coronary artery plaque volume and obesity in patients with diabetes: the factor-64 study. , 2014, Radiology.

[17]  F. Rybicki,et al.  Prognostic Value of Nonobstructive and Obstructive Coronary Artery Disease Detected by Coronary Computed Tomography Angiography to Identify Cardiovascular Events , 2014, Circulation. Cardiovascular imaging.

[18]  T. Villines,et al.  Coronary CT angiography versus intravascular ultrasound for estimation of coronary stenosis and atherosclerotic plaque burden: a meta-analysis. , 2013, Journal of cardiovascular computed tomography.

[19]  A. Menter,et al.  Burden of Disease: Psoriasis and Psoriatic Arthritis , 2013, American Journal of Clinical Dermatology.

[20]  Jashin J. Wu,et al.  Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. , 2012, Archives of dermatology.

[21]  A. Kyrgidis,et al.  Association of ustekinumab and briakinumab with major adverse cardiovascular events , 2012, Dermato-endocrinology.

[22]  Breanne N. Gjurich,et al.  The IL-17A/IL-17RA Axis Plays a Proatherogenic Role via the Regulation of Aortic Myeloid Cell Recruitment , 2012, Circulation research.

[23]  Y. Iwakura,et al.  Interleukin-17A Deficiency Accelerates Unstable Atherosclerotic Plaque Formation in Apolipoprotein E-Deficient Mice , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[24]  A. Quyyumi,et al.  Role of Interleukin 17 in Inflammation, Atherosclerosis, and Vascular Function in Apolipoprotein E–Deficient Mice , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[25]  M. Lebwohl,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 , 2011, The British journal of dermatology.

[26]  D. Böckler,et al.  Inhibition of IL-17A Attenuates Atherosclerotic Lesion Development in ApoE-Deficient Mice1 , 2009, The Journal of Immunology.

[27]  A. Troxel,et al.  The risk of stroke in patients with psoriasis. , 2009, The Journal of investigative dermatology.

[28]  S. Pocock,et al.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. , 2007, Preventive medicine.

[29]  G. Lowe,et al.  Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. , 2007, Arthritis and rheumatism.

[30]  S. Feldman,et al.  A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a clinically significant endpoint in the assessment of psoriasis. , 2004, Journal of the American Academy of Dermatology.

[31]  P. Ridker Clinical application of C-reactive protein for cardiovascular disease detection and prevention. , 2003, Circulation.

[32]  M. Pfeffer,et al.  Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. , 1998, Circulation.