Dermatology

Plaque Psoriasis

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Does Biologic Therapy for Psoriasis Quell Coronary Inflammation?

clinical topic updates by Joel M. Gelfand, MD, MSCE

Overview

Some biologic therapies used in the treatment of plaque psoriasis have shown favorable effects on biomarkers of cardiovascular risk, such as C-reactive protein, tumor necrosis factor, and interleukin 6 (IL-6). As the science of predicting cardiovascular risk continues to unfold, traditional risk factor reduction in patients with psoriasis remains key.

Expert Commentary

Joel M. Gelfand, MD, MSCE

James J. Leyden, M.D. Endowed Professor in Clinical Investigation
Professor, Dermatology and Epidemiology
Vice-Chair, Clinical Research
Medical Director, Dermatology Clinical Studies Unit and Psoriasis and Phototherapy Treatment Center
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

“During the first conversation that we have with our patients about psoriasis and cardiovascular risk, we must emphasize the importance of screening and management of traditional cardiovascular risk factors, and we should encourage the adoption of healthy lifestyle changes.” 

Joel M. Gelfand, MD, MSCE

To understand how biologic therapies might translate into a reduction in cardiovascular events in psoriasis, large, placebo-controlled, prospective studies with long-term follow-up would be needed. However, structural changes (eg, atherosclerotic progression) can take several months or even years to observe, and patients with psoriasis should not be assigned to a placebo for such extended durations. We have been analyzing blood-based cardiometabolic biomarkers, and we have also measured aortic vascular inflammation (AVI) in several of our trials because this approach has been shown to be predictive of future cardiovascular events and these changes occur rapidly with therapies that are known to lower cardiovascular risk, such as statins. 

In our 2018 study comparing the effects of adalimumab, phototherapy, or placebo on vascular inflammation and cardiovascular biomarkers, we reported a reduction in inflammatory markers in the adalimumab group for C-reactive protein, tumor necrosis factor, IL-6, and glycoprotein acetylation, whereas C-reactive protein and IL-6 were reduced in the phototherapy arm. We did not observe a reduction in AVI with either adalimumab or phototherapy. In other studies, we have seen that secukinumab appears to be somewhat neutral in its effects on these markers and on AVI. In some ways, this was unexpected because the hypothesis had been that marked skin clearance with secukinumab would be paralleled by a marked reduction in these markers. In contrast, in our recent study on the effects of ustekinumab on vascular inflammation in psoriasis, ustekinumab did appear to reduce AVI vs placebo at week 12; however, that effect was transient and it did not persist when patients stayed on the drug for 1 year. Thus, our findings demonstrated that blockade of IL-12 and/or IL-23 may transiently reduce AVI, with a more durable reduction in inflammatory cytokines associated with cardiovascular disease; however, the clinical significance of these findings is uncertain. 

In clinical practice, patients with psoriasis benefit from education about the increased cardiovascular risk that is associated with this disease. We know that our patients with psoriatic disease tend to have higher rates of hypertension, diabetes, obesity, and hyperlipidemia. These factors are often underdiagnosed, and, when they are diagnosed, they tend to be undertreated. We also know that the prevalence of these risk factors increases with the severity of skin disease. During the first conversation that we have with our patients about psoriasis and cardiovascular risk, we must emphasize the importance of screening and management of traditional cardiovascular risk factors, and we should encourage the adoption of healthy lifestyle changes. For example, among patients with psoriasis, my experience has been that only about 25% of those in whom statins are recommended are taking them. If we could solve that problem alone, we would dramatically improve the life expectancies of our patients. 

References

Choi H, Uceda DE, Dey AK, et al. Treatment of psoriasis with biologic therapy is associated with improvement of coronary artery plaque lipid-rich necrotic core: results from a prospective, observational study. Circ Cardiovasc Imaging. 2020;13(9):e011199. doi:10.1161/CIRCIMAGING.120.011199

Dey AK, Gaddipati R, Elnabawi YA, et al. Association between soluble lectinlike oxidized low-density lipoprotein receptor-1 and coronary artery disease in psoriasis. JAMA Dermatol. 2020;156(2):151-157. doi:10.1001/jamadermatol.2019.3595

DiMinno MND, Iervolino S, Peluso R, Scarpa R, Di Minno G; 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(3):705-712. doi:10.1161/ATVBAHA.110.214585

Elmets CA, Leonardi CL, Davis DMR, 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(4):1073-1113. doi:10.1016/j.jaad.2018.11.058 

Gelfand JM, Shin DB, 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(1):85-93.e2. doi:10.1016/j.jid.2019.07.679

Gelfand JM, Shin DB, Duffin KC, 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(9):1784-1793.e2. doi:10.1016/j.jid.2020.01.025

Masson W, Lobo M, Molinero G, Rossi E. Should all patients with psoriasis receive statins? Analysis according to different strategies. An Bras Dermatol. 2019;94(6):691-697. doi:10.1016/j.abd. 2019.03.001 

Mehta NN, 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. doi:10.1161/CIRCIMAGING.117.007394

Melander O, Newton-Cheh C, Almgren P, et al. Novel and conventional biomarkers for the prediction of incident cardiovascular events in the community. JAMA. 2009;302(1):49-57. doi:10.1001/jama.2009.943

Sajja A, Abdelrahman KM, Reddy AS, et al. Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time. JCI Insight. 2020;5(22):142534. doi:10.1172/jci.insight.142534

Joel M. Gelfand, MD, MSCE

James J. Leyden, M.D. Endowed Professor in Clinical Investigation
Professor, Dermatology and Epidemiology
Vice-Chair, Clinical Research
Medical Director, Dermatology Clinical Studies Unit and Psoriasis and Phototherapy Treatment Center
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

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