SPIN2019

Conference summaries


PSORIASIS

Effects of biotherapy on vascular disease in psoriasis

Presented by: Nehal N. Mehta, MD, MSCE, FAHA
Chief, Lab of Inflammation and Cardiometabolic Diseases,
National Heart Lung and Blood Institute, National Institutes of Health, MD; USA

  • Psoriasis (PsO) is a chronic, complex autoimmune disease characterized by erythematous, scaly patches over extensor aspects of skin and is associated with joint involvement in about one-third of patients.
  • An association between PsO and cardiovascular (CV) diseases has been a topic of dilemma, and many studies have shown an increased risk of cardiovascular morbidity in patients with PsO.
  • Heart attack remains the leading cause of death world-wide and atherosclerosis is the leading cause of heart attack and is accelerated by inflammation [1].
  • PsO can be considered a human model of inflammatory atherogenesis with immune activation, systemic inflammation and lipoprotein dysfunction, all leading to myocardial infarction (MI).
  • Due to the association of PsO with CV disease, patients with severe PsO have a 50% increase risk of mortality and an estimated 5 years loss of life [2].
  • One out of every 2 patients with severe PsO will experience an MI [3].
  • PsO is a systemic inflammatory disease which was proven in 2011 to be associated with vascular inflammation thanks to nuclear techniques [4].
  • The amount of vascular inflammation is directly related to PASI scores, even after adjustment for CV risk factors [5].
  • Anti-TNF therapy proved useful in reducing the vascular inflammation in a multi-center, randomized control trial of 3 therapies; inactive, skin directed, and biologic directed [6].
  • The major comparison was FDG-PET uptake.
  • The results showed that anti-TNF therapy had anti-inflammatory effects on the skin and blood compared to phototherapy.
  • Both anti-TNF therapy and phototherpy had a neutral impact on MI as assessed by 18F-FDG PET/CT compared with placebo.
  • Anti-TNF therapy had no impact on glucose metabolism with effects on reducing inflammation biomarkers including GlycA, TNF-alpha and high-sensitivity C-reactive protein (hs-CRP).
  • Soon after the CANTOS study published data of (non-psoriatic) patients who had had an initial MI.
  • These patients were randomized to IL1β or placebo, with the primary endpoint being a secondary MI.
  • This study proved a 15% positive reduction in MI, with most benefit observed in those with hs-CRP ≥2 mg/L compared to those with lower hs-CRP levels [7].
  • Coronary computed tomography angiography (CCTA) proved that the total plaque burden in PsO patients, which is non-calcified, is increased by 20% compared to healthy volunteers, so there is thickening of the coronary vessel wall before any symptoms appear [7-8].
  • Non-calcified plaque is the most common cause of plaque rupture and MI.
  • PsO is associated with low attenuation and positive remodelling, even at an early age; relatively that young PsO patients (46 years old) have a similar high-risk plaque presence as older hyperlipidemia patients (60 years old) [9]. See Table 1.
  • In a study of moderate to severe PsO patients with a new biologic therapy (n = 89), compared to those refusing biologic therapy (n = 32), baseline and 12-month CCTA scans were compared for change in total plaque.
  • There was a significant change observed in inflammation (p <0.001) for biologic therapy; 5% and 7% reductions in total and non-calcified plaque burden, compared to a 2% and 5% increase in patients not receiving biologic therapy [10], see Table 2.
  • Additionally, there was a decrease in the necrotic core of 57% (the part of the plaque that ruptures) and a 33% progression in the patients without biologic treatment, see Table 3.
  • Exploratory analyses suggest that anti-TNF therapy had an insignificant effect on total plaque and non-calcified plaque burdens whereas anti-IL17 therapies were associated with a significant drop in these burdens, see Table 4.
  • These preliminary data are currently being investigated in randomised trials.

Conclusions

  • The lipid stream can become non-calcified plaque and with the inflammation observed in PsO patients, a necrotic core can form, and high-risk plaque is developed.
  • It is probably this plaque type causing myocardial infarction in PsO patients.
  • Biologic therapy may retard or even reverse this progression.


References

References


  1. 1. Mehta PK, Beltrame JF. Myocardial infarction with non-obstructive coronary arteries: a humbling diagnosis in 2018. Heart. 2019 Apr;105(7):506-507
  2. 2. Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296:1735-41
  3. 3. Mehta NN, Yu Y, Pinnelas R, Krishnamoorthy P, et al. Attributable risk estimate of severe psoriasis on major cardiovascular events. Am J Med. 2011;124:775.e1-6.
  4. 4. 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;147:1031-9
  5. 5. Dey AK, Joshi AA, Chaturvedi A, et al. Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography. JAMA Cardiol. 2017;2:1013-1018
  6. 6. 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:e007394.
  7. 7. Ridker PM, Everett BM, Thuren T, et al., for the CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med 2017; 377:1119-1131.
  8. 8. Salahuddin T, Natarajan B, Playford MP, et al. Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis. Eur Heart J. 2015;36:2662-5.
  9. 9. Lerman JB, Joshi AA, Chaturvedi A, et al. Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study. Circulation. 2017;136:263-276.
  10. 10. Elnabawi YA, Dey AK, Goyal A, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study. Cardiovasc Res. 2019;115:721-728.

Presenter disclosure(s): [none provided]

Written by: Johanna Chester, BA

Reviewed by: Martina Lambertini, MD


All report

Welcome to the SPIN 2019 Highlights

Jo Lambert, MD, PhD

With this collection of summaries from selected presentations at SPIN 2019, and interviews with international experts, we hope to share with you some of the highlights of this year’s congress. The international network met … [ Read all ]

SUMMARIES

ATOPIC DERMATITIS & PSORIASIS

Atopic dermatitis and psoriasis: On a spectrum?

Presented by: Emma Guttman-Yassky, MD, PhD

INFLAMMATORY SKIN DISEASES

PSORIASIS

Which drug for which patient?

Presented by: Emilie Sbidian, MD, PhD

PSORIASIS

Effects of biotherapy on vascular disease in psoriasis

Presented by: Nehal N. Mehta, MD, MSCE, FAHA

SYSTEMIC THERAPIES

Classical systemic therapies – Methotrexate

Presented by: Rolland Gyulai, MD, PhD, DSc

SMALL MOLECULES

Small molecules, apremilast, and beyond

Presented by: Richard G.B. Langley, MD

PSORIASIS

Treatment goals in psoriasis

Presented by: Ulrich Mrowietz, MD

PSORIASIS

Combined therapy in psoriasis

Presented by: Pablo Coto-Segura, MD, PhD

MEASURING OUTCOMES

PSORIASIS & ADHERENCE

How can we support optimal medication adherence?

Presented by: Rachael Thorneloe, MD