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.