Sulzberger lecturer provides in-depth look at psoriasis comorbidities

At AAD 2017, Joel M. Gelfand, MD, MSCE, was honored as the recipient of the Marion B. Sulzberger, MD, Memorial Award and Lectureship. In his talk titled “Getting to the heart (and other comorbidities) of psoriasis,” Dr. Gelfand discussed the findings from research investigating associations between psoriasis and comorbidities and their relevance for providing comprehensive medical care for patients with psoriasis.

Concluding his talk, Dr. Gelfand expanded on a quote from Dr. Francis Peabody’s essay, “The Care of the Patient”, written 90 years ago.

“Dr. Peabody stated, ‘…the secret of the care of the patient is in caring for the patient.’ For the patient with psoriasis, that means we need to look beyond the skin,” said Dr. Gelfand, Professor of Dermatology and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

Establishing evidential support

Focusing primarily on associations between psoriasis and cardiovascular disease, Dr. Gelfand highlighted results from population-based epidemiological studies, including those from his own clinical research laboratory analyzing data in a prospectively maintained medical record database in the United Kingdom.

“Our studies showed an independent, dose-response relationship between psoriasis severity and risks of major adverse cardiovascular events, ie., myocardial infarction, stroke, and cardiovascular disease-related mortality. Subsequently, numerous papers have been published investigating the association between psoriasis and cardiovascular risk, and results from nine meta-analyses covering more than 500,000 patients with psoriasis and more than 29 million controls largely confirm our initial findings,” he said.

Findings from laboratory investigations provide insights into the potential biological mechanisms underlying the association between psoriasis and cardiovascular disease and provide proof of principle that inflammation restricted to the skin can lead to systemic vascular complications, Dr. Gelfand said.

In addition, clinical studies using [18F]-fluorodeoxyglucose positron emission tomography/computed tomography imaging show that as psoriasis severity increases so does aortic and subcutaneous fat inflammation.

“A finding that subcutaneous fat under psoriatic plaques expresses miRNAs that modulate lipid metabolism suggests there is communication between the skin and the fat and that it plays a role in mediating some of the connections we are seeing between psoriasis and cardiometabolic disease,” Dr. Gelfand said.

Next: Mitigating cardiovascular risk

Mitigating cardiovascular risk

Extrapolating from prospectively collected cohort data on psoriasis and mortality, which was presented at the AAD late breaking research session by his post-doctoral fellow Megan Noe, MD, MPH, FAAD, Dr. Gelfand suggested that worldwide there are approximately 45,000 premature deaths each year attributable to severe (i.e., psoriasis affecting 10% or more of the body surface area) psoriasis that is independent of traditional risk factors for mortality.

“This observation begs the critical question, should psoriasis be aggressively treated to lower the risk of cardiovascular disease,” he said.

Observational data from the rheumatoid arthritis literature showing that treatment with both tumor necrosis factor (TNF) inhibitors and methotrexate lower the risk of cardiovascular disease suggest the answer is yes.

“Recommending use of aggressive systemic therapies in patients with psoriasis to prevent cardiovascular disease, however, must have a strong evidence base, and there are no data from randomized controlled trials on the potential cardioprotective effects of treatments used for psoriasis,” Dr. Gelfand said. 

Dr. Gelfand is leading a series of clinical trials (Vascular Inflammation in Psoriasis, NCT01553058, 01866592, 02187172, 03082729, and 02690701) to address the need for data from rigorous research to determine whether aggressive psoriasis management has a role for lowering cardiovascular risk. Results from the primary endpoint analysis are available from one study randomizing patients to adalimumab (Abbvie, Humira), phototherapy, or placebo that show no statistically significant benefit of either adalimumab or phototherapy for reducing aortic inflammation compared with control.

One potential explanation for the lack of effect is that direct action of the intervention on the target tissue may be necessary for reducing vascular inflammation, Dr. Gelfand said.

“The most impressive findings on reducing aortic inflammation with systemic treatment have

been in clinical trials with statins, which are small molecules. Perhaps adalimumab, a large monoclonal antibody, does not penetrate the aorta wall,” Dr. Gelfand said.

More insights from this study are expected to come from biomarker and exploratory analyses, and results are awaited from other Vascular Inflammation in Psoriasis trials investigating other systemic therapies [ustekinumab (Stelara, Janssen Biotech), secukinumab (Cosentyx, Novartis Pharmaceuticals, and apremilast (Otezla, Celgene)] for psoriasis.

Next: Current considerations fro clinical practice

Current considerations for clinical practice

Translating what is known about psoriasis and comorbidities to clinical care, Dr. Gelfand said that dermatologists need to be aware of the existing relationships and the potential consequences on physical and emotional health and integrate the information into their management decisions. He noted that in addition to data associating psoriasis with cardiovascular disease, there is strong evidence linking psoriasis with metabolic syndrome, diabetes, psoriatic arthritis, mood disorders, Crohn’s disease and T cell lymphoma. In addition, evidence is emerging to show higher rates of sleep apnea, nonalcoholic steatohepatitis, chronic obstructive pulmonary disease, renal disease, peptic ulcer disease, and sexual dysfunction among patients with psoriasis.

Outlining specific recommendations for care, Dr. Gelfand said dermatologists should educate psoriasis patients about the connection between their skin disease and cardiovascular risk and either personally screen these patients for cardiovascular risk factors according to US Preventative Health Task Force guidelines or refer them back to their primary care physician for this evaluation.
Recognizing that certain diseases are more prevalent in patients with psoriasis and considering potential effects of immune modulating treatments on those comorbidities, Dr. Gelfand also recommended that psoriasis patients be referred for age-appropriate cancer screening, kept current with recommended vaccinations, particularly influenza and pneumonia, and screened for mood disorders.

He also discussed a personalized medicine approach to selection of biologic therapies for patients with psoriasis that takes into account the potential to benefit or adversely impact comorbidities.

For more information on psoriasis and comorbid diseases, readers can refer to two articles authored by Dr. Gelfand and colleagues and published in the March 2017 issue of the Journal of the American Academy of Dermatology:  Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol. 2017;76(3):393-403.   Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: Epidemiology. J Am Acad Dermatol. 2017;76(3):377-390.

Disclosures: Dr. Gelfand served as a consultant for Coherus (DSMB), Dermira, Janssen Biologics, Merck (DSMB), Novartis Corp, Regeneron, Dr Reddy’s labs, Sanofi and Pfizer Inc., receiving honoraria; and receives research grants (to the Trustees of the University of Pennsylvania) from Abbvie, Janssen, Novartis Corp, Regeneron, Sanofi, Celgene, and Pfizer Inc.; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly and Abbvie. Dr. Gelfand is a co-patent holder of resiquimod for treatment of cutaneous T cell lymphoma.