Enfermedad Cardiovascular en Psoriasis

Published in Dermatology and

Journal Scan / Research · February 25, 2019

Coronary Artery Plaque Characteristics and Treatment With Biologic Therapy in Severe Psoriasis

Cardiovascular research

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TAKE-HOME MESSAGE

• In patients with moderate to severe psoriasis and low Framingham cardiovascular risk scores at baseline, treatment with TNF-α inhibitors (adalimumab, etanercept), interleukin-12/23 inhibitors (ustekinumab), or interleukin-17 inhibitors (secukinumab, ixekizumab) was associated with a reduction in noncalcified coronary plaque burden, visualized with coronary CTA.

• These findings suggest that treating patients with moderate to severe psoriasis patients with biologic therapy may confer cardiovascular benefits.

– InYoung Kim, MD, PhD

Dermatology

Written by



Anthony Fernandez MD, PhD

Biologics and Psoriatic Disease: Have We Finally Detected a Mechanism Linking Treatment to Cardiovascular Risk Improvement?

Following a hallmark study revealing that psoriasis is an individual risk factor for future myocardial infarction (MI), an explosion of research has solidified an association between moderate to severe psoriasis and increased risk of cardiovascular disease.^1,2 More recently, imaging studies using FDG-PET/CT have shown that patients with psoriasis have inflammation in numerous organs, including the aorta and other vascular beds, compared with healthy individuals without psoriasis.3 Thus, a fundamental hypothesis has been that adequately treating moderate to severe psoriasis should decrease vascular inflammation, and thus, future risk of cardiovascular events.

Unfortunately, results of studies exploring the relationship between adequately treating psoriasis and decreasing future cardiovascular events have been conflicting. Epidemiologic studies using claims databases suggest that treating psoriasis with biologics decreases cardiovascular events compared with treating psoriasis with phototherapy and methotrexate.^4,5 However, several relatively well-designed, prospective studies have recently failed to show that biologic therapy decreases aortic vascular inflammation in moderate to severe psoriasis patients.^6,7,8 These studies do, however, show a trend in decreased biomarkers of vascular inflammation, such as hsCRP, with biologic treatment. Although lack of positive impact on vascular inflammation may be surprising, trends in decreased biomarkers suggest that study designs with more patients followed for longer time periods may allow detection of positive results. Nevertheless, this remains to be seen.

Results of this study by Elnabawi et al suggest that researchers may have found a mechanism alternative to direct effect on vascular inflammation that links biologic therapy to decreased risk of cardiovascular events. In a prospective, observational study, 215 patients were followed for 1 year, with 121 biologic- and systemic therapy–naïve patients initiated on biologic therapy. The other patients were treated with topical medications and phototherapy. After following patients with serial coronary computed tomography angiography (CCTA) over 1 year, the patients treated with biologics (anti-TNF, anti-IL12/23, or anti-23 therapies) demonstrated significant decreases in noncalcified coronary plaque burden and reduction in necrotic core, with no effect on fibrous burden, compared with the nonbiologic-treated cohort. The decrease in noncalcified plaque burden was significant even after adjustment for traditional cardiovascular risk factors. Additionally, reduction in coronary plaque burden was significantly greater with anti-IL17 therapy compared with anti-IL12/23 therapy and no biologic therapy. On the other hand, there was progression of coronary artery disease with conversion of fibrous burden to fibro-fatty burden of plaques in the nonbiologic-treated cohort.

Although this is a relatively small study following patients for a short period of time, it may be significant. Could decreasing noncalcified coronary plaque burden and coronary plaque characteristics be the key to preventing future myocardial infarctions and strokes in psoriasis patients who are known to be at risk for developing them? Recently, it has been shown that CCTA plaque features are important for defining accurate cardiovascular risk.⁹ Although the progression rate of subclinical atherosclerosis on CCTA in psoriasis patients is unknown, lipid-rich plaque and necrotic core, both of which decreased with biologic therapy in the study by Elnabawi et al, are known to be inflammation-driven. This inflammatory component would support the positive results that may truly be related to biologic therapy. The results of this study are exciting, but there are important limitations preventing definitive statements concerning the impact of biologic therapy on coronary plaque burden and characteristics in psoriasis patients.

Importantly, patients in the study by Elnabawi et al had low cardiovascular risk per Framingham score. Also, patients had a relatively low median PASI score of 8.6. These characteristics make it attractive to hypothesize that psoriasis patients with higher Framingham scores and/or PASI scores may have more significant improvement in coronary plaque burden and plaque characteristics when treated with biologics than seen in the current study. This is underscored by the fact that patients in the Elnabawi study had a noncalcified coronary plaque burden that correlated with increasing PASI scores. Hopefully larger, better-designed studies in the future will include psoriasis patients with a wider variety of disease severity and cardiovascular risk to further explore such hypotheses.

In short, more work needs to be done, and we are only beginning to understand the true relationship between psoriasis and cardiovascular disease. For the moment, however, the study by Elnabawi et al appears to have potentially uncovered an exciting piece of the puzzle concerning how biologic therapy may positively impact cardiovascular disease risk in psoriasis patients.

References

1. Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741. https://jamanetwork.com/journals/jama/fullarticle/203598
2. Sobchak C, Eder L. Cardiometabolic disorders in psoriatic disease. Curr Rheumatol Rep. 2017;19(10):63. https://link.springer.com/article/10.1007%2Fs11926-017-0692-2
3. Mehta NN, Yu Y, Saboury B, et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol. 2011;147(9):1031-1039. https://jamanetwork.com/journals/jamadermatology/fullarticle/1105159
4. Wu JJ, Sundaram M, Cloutier M, et al. The risk of cardiovascular events in psoriasis patients treated with tumor necrosis factor-α inhibitors versus phototherapy: an observational cohort study. J Am Acad Dermatol. 2018;79(1):60-68. https://www.jaad.org/article/S0190-9622(18)30335-9/fulltext
5. Wu JJ, Guerin A, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90. https://www.jaad.org/article/S0190-9622(16)30593-X/fulltext
6. Bissonnette R, Harel F, Krueger JG, et al. TNF-α antagonist and vascular inflammation in patients with psoriasis vulgaris: a randomized placebo-controlled study. J Invest Dermatol. 2017;137(8):1638-1645. https://www.jidonline.org/article/S0022-202X(17)31213-7/fulltext
7. Gelfand JM, Shin DB, Joshi AA, et al. Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers: a randomized placebo-controlled trial. Circ Cardiovasc Imaging. 2018;11(6):e007394. https://www.ahajournals.org/doi/full/10.1161/CIRCIMAGING.117.007394
8. Gelfand JM, et al. The VIP-S trial: study to evaluate the effect of secukinumab compared to placebo on aortic vascular inflammation in subjects with moderate-to-severe plaque psoriasis. Annual AAD Meeting 2019; S034 (poster 11034); March 2, 2019; Washington, DC.
9. Bittencourt MS, Hulten E, Ghoshhajra B, et al. Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ Cardiovasc Imaging. 2014;7(2):282–291. https://www.ahajournals.org/doi/full/10.1161/CIRCIMAGING.113.001047

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Abstract

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.

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Copyright © 2019 Elsevier Inc. All rights reserved.

Coronary Artery Plaque Characteristics and Treatment With Biologic Therapy in Severe Psoriasis: Results From a Prospective Observational Study

Cardiovasc. Res. 2019 Feb 05;[EPub Ahead of Print], YA Elnabawi, AK Dey, A Goyal, JW Groenendyk, JH Chung, AD Belur, J Rodante, CL Harrington, HL Teague, Y Baumer, A Keel, MP Playford, V Sandfort, MY Chen, B Lockshin, JM Gelfand, DA Bluemke, NN Mehta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.