Mounting evidence shows that psoriasis is frequently comorbid with cardiovascular (CV) disorders, and some studies have shown a dose-response effect between the 2 diseases.1 The more severe the psoriasis, the likelier a patient is to have CV concerns. Now, recent evidence from a population cohort study has shown a dose-response effect for psoriasis severity and mortality risk.2
Using the United Kingdom’s Health Improvement Network database of 8760 men and women with psoriasis and 87,600 adults without psoriasis, Noe and colleagues found that patients with psoriasis covering >10% of their body surface area were 1.79 times more likely to die compared with their healthy counterparts, even after adjusting for body mass index and alcohol and tobacco use.2 People with psoriasis tended to have higher incidence of chronic kidney disease, chronic obstructive pulmonary disease, diabetes, and myocardial infarction.2
“Physicians should be aware that patients with psoriasis have an increased risk of major CV events and mortality independent of traditional risk factors,” noted Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania Perelman School of Medicine in Philadelphia. “This risk is most clinically important in psoriasis patients who require treatment with systemic or phototherapy or who have more than 10% of the body surface area affected by psoriasis.”
Do Biologics Protect Psoriasis Patients From CV Risk?
A recent study suggests that treating patients for psoriasis with biologics may reduce their risk for CV events. Wu and colleagues found that patients with psoriasis who were treated with tumor necrosis factor-alpha inhibitors (TNF-alpha inhibitors; n=11,410) had fewer CV events compared with those who received phototherapy (n=12,433).3 At 4 months after treatment initiation, patients who received TNF inhibitors had a statistically significant difference in CV events vs those who received phototherapy (adjusted hazard ratio 0.77; 95% CI, 0.60-0.99; P =.046).3 For each 6-month exposure to TNF inhibitors, patients had an 11% risk reduction of CV events vs those treated with phototherapy (P <.05).3
In early biologics trials, preliminary evidence suggested that biologics could be harmful to patients with psoriasis at high risk for CV events.4 Yet 1 early meta-analysis of 22 randomized control trials with 10,183 patients did not demonstrate that biologics prevented major adverse CV events (MACEs), defined as a myocardial infarction, cerebrovascular incident, or CV death. There was no significant difference in MACE rates for patients who received therapy with anti-interleukin (IL)-12/IL-23 antibodies or anti-TNF-alpha agents.4
A later 38-study meta-analysis (N=18,024) confirmed that biologics did not cause MACEs in patients with psoriasis who were also at substantial risk for CV disease compared with placebo (odds ratio [OR] 1.45; 95% CI, 0.34-6.24).5 Only 9 of the randomized controlled trials reported MACEs in 10 patients. Moreover, there were no significant differences among the biologics: TNF-alpha inhibitors (adalimumab, etanercept, and infliximab; OR 0.67; 95% CI, 0.10-4.63), anti-IL-17A agents (secukinumab and ixekizumab; OR 1.00; 95% CI, 0.09-11.09), or ustekinumab (OR 4.48; 95% CI, 0.24-84.77).5
“These results should be interpreted with caution, given the short duration of follow-up [median, 12 weeks] and the characteristics of patients participating in [randomized controlled trial]s,” explained lead author Watcharee Rungapiromnan, a PhD candidate at the University of Manchester in the United Kingdom. “Well-designed observational studies that involve larger numbers of patients and longer durations of treatment exposure reflecting routine clinical practice are required to better examine the impact of biologic therapies on the risk of MACEs in patients with psoriasis.”
One of the putative effects of biologics is their anti-inflammatory property.6,7 To test this hypothesis, Bissonnette and colleagues compared the TNF-alpha antagonist adalimumab (n=54) vs placebo (n=53) on vascular inflammation of patients with psoriasis.7 At the end of the 52-week study, there was only a modest difference in the primary end point, the vessel wall target-to-background ratio from the ascending aorta, as measured by positron emission tomography-computed tomography (target-to-background ratio −0.006; 95% CI, −0.049 to 0.038; P =.796). There was, however, an increase in target-to-background ratio in the carotid arteries at 52 weeks (target-to-background ratio 0.027; 95% CI, 0.000-0.054; P =.046).7
“When considering psoriasis therapies, dermatologists should think about cardiac risk factors,” said Mark G. Lebwohl, MD, professor and system chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York City. “For patients with many risk factors, treatments that have been shown in registries to reduce [CV] mortality should be considered. TNF blockers have certainly demonstrated a protective effect.”
Best Practices for Patients With Psoriasis
To provide guidance to dermatologists and clinicians who treat patients with moderate to severe psoriasis, Strohal and colleagues convened an interdisciplinary Delphi survey, including a cardiologist, to discuss psoriasis comorbidity management.8
Although there was unanimous agreement among the panelists regarding screening for CV comorbidities, a slightly lower 83% agreed that psoriasis is an independent contributor for CV disease.8 Panelists concurred that on diagnosing psoriasis and each subsequent year, clinicians should screen patients for hypertension, weight, waist circumference, lipids, fasting glucose, hemoglobin A1C, and smoking status. They did not, however, reach consensus about when to refer to cardiologists or other specialists. Most panelists agreed that treatment for CV comorbidities should be the purview of a cardiologist, endocrinologist, or family physician.8
Because of the Delphi survey and increasing evidence linking psoriasis to CV risk, dermatology professor and department head Robert Strohal, MD, from the Federal Academic Teaching Hospital of Feldkirch in Austria, hopes his dermatology colleagues will gain “better access to biologics, preferential treatment with the new biologics and not biosimilars, and biologics with a longer half-life.”
Dr Gelfand concurred, “Patients with psoriasis should be targeted for screening for [CV] risk factors such as diabetes, hypertension, and hypercholesterolemia according to current national guidelines, and have these known risk factors well controlled. For those who smoke, they should be encouraged to quit; for those who are overweight or obese, they should be encouraged to eat a healthy diet and try to lose weight.”
Limitations & Disclosures
1. Gelfand JM. Does biologic treatment of psoriasis lower the risk of cardiovascular events and mortality? A critical question that we are only just beginning to answer. J Am Acad Dermatol. 2018;79(1):69-70.
2. Noe MH, Shin DB, Wan MT, Gelfand JM. Objective measures of psoriasis severity predict mortality: a prospective population-based cohort study. J Invest Dermatol. 2018;138(1):228-230.
3. 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.
4. Ryan C, Leonardi CL, Krueger JG, et al. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. JAMA. 2011;306(8):864-871.
5. Rungapiromnan W, Yiu ZZN, Warren RB, Griffiths CEM, Ashcroft DM. Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol. 2017;176(4):890-901.
6. Lebwohl M. Does treatment of psoriasis reduce cardiovascular comorbidities? J Invest Dermatol. 2017;137(8):1612-1613.
7. 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.
8. Strohal R, Kirby B, Puig L, et al. Psoriasis beyond the skin: an expert group consensus on the management of psoriatic arthritis and common co-morbidities in patients with moderate-to-severe psoriasis. J Eur Acad Dermatol Venereol. 2014;28(12):1661-1669.