Psoriasis Update: Part 3

Comorbidities and Cardiovascular Status of Psoriasis Patients

Craig Leonardi, MD

In this final session of the psoriasis discussion, Dr Leonardi discussed co-morbidities and the cardiovascular status of patients with psoriasis.

Metabolic Syndrome and Psoriasis

Psoriasis patients are at an increased risk for the metabolic syndrome. There are meta-analyses that have been performed that have shown that these patients have an increased risk for type 2 diabetes, hyperlipidemia, hypertension, and obesity.

Myocardial Infarction (MI) in Patients with Psoriasis

Joel Gelfand and colleagues conducted a cohort study of 130,976 to determine the risk of MI in psoriasis patients. The results showed that patients with severe psoriasis had a marked increase of MI as compared to those patients with mild disease.

Why do psoriasis patients have increased cardiovascular risks?
  • The use of dyslipidemic therapies, such as corticosteroids, acitretin, and cyclosporine
  • The increased prevalence of associated and/or independent risk factors: smoking, obesity, hypertension, and alcohol misuse
  • Uncontrolled inflammation leading to endothelial dysfunction and dyslipidemia
Does the treatment of a chronic inflammatory disease reduce cardiovascular risk?

A retrospective cohort study demonstrated that the use of methotrexate reduces the incidence of cardiovascular disease in patients with psoriasis. It is also shown that treatment with TNF blockers decreases the mortality risk in patients with rheumatoid arthritis. In psoriasis, TNF-inhibitor treated patients had a 48 percent reduction of MI risk.

What about CV risk in the setting of IL 12/23 inhibition?

Briakinumab’s Phase III demonstrated an increased number of CV events ( 5 compared to 0 in placebo) and MACE signals were also seen in the ustekinumab phase III trial as well.

Association between biologic therapies for chronic plaque psoriasis and cardiovascular events- a meta-analysis

This study looked at 19 high quality studies. In the TNF studies, only two MACE events were reported (one in treated/one in untreated). In the 12/23 inhibitors, there were 10 events compared to 1 in placebo. Statistics show that the TNF antagonists are not associated with MACE.

In the JAMA article that was published, the conclusions (above) had to be tempered. Tzellos et al re-looked at the data and published a re-analysis of the data using different statistical modeling (they used the PETO method), they found no increased risk of MACE events.

Risk of MACE in IL 12/23 Psoriasis Trials
  • Background rate of MACE 0.0012/pt-yr, which was based on the aggregated rate in the placebo group for all 22 studies.
  • Rate in the IL-12/23 studies was 0.012 (10 times the background rate)
What are some of the next steps that need to be taken?
  1. Pay attention to the issue
  2. Emerging therapies-need to wait for phase III data (blocking 12/23 downstream)
  3. Pay attention to Amgen’s development efforts on brodalumab in which brodalumab and ustekinumab are involved in a comparator trial
  4. PSOLAR (Janssen registry) may provide data
Final Comments

American Academy of Dermatology Guidelines Recommends Monitoring; Basic CV screening includes:

Laboratory evaluation

  • Fasting comprehensive metabolic panel
  • Fasting lipids
  • Blood pressure
  • Assessment of overweight/obese status

Inquiry

  • Alcohol
  • Smoking
  • Depression
  • Arthritis

Ustekinumab: recommendations for use

  • Consider all options when selecting a biologic
  • Know that psoriasis pts typically have multiple cardiac risk factors
  • Consider starting with low (45mg) dose regardless of patient weight
  • Consider adding ASA 81mg QD
  • Await further analysis (FDA, EMA, Abbott, Janssen, Amgen)
  • Remember that all new drugs are ‘new’

Consider additional specialty care for psoriasis patients