Study: Apremilast Associated With Fat Loss in Patients With Psoriasis

Research shows that patients with a severe form of psoriasis have a higher risk of death from cardiovascular disease.

In addition to treating psoriasis, apremilast (Otezla) may help people with psoriasis lose weight to enhance their overall cardiovascular health, which is a comorbidity for patients with the skin condition. This benefit from the drug was shown in a new analysis from investigators at the Perelman School of Medicine at the University of Pennsylvania.

Apremilast is an oral, small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP) and PDE4 inhibition results in increased intracellular cAMP levels, which is considered to indirectly modulate the production of inflammatory mediators. Additionally, it is currently indicated for the treatment of adult patients with active psoriatic arthritis, plaque psoriasis, and adult patients with oral ulcers associated with Behçet's Disease.

“The study’s most provocative findings are that the drug decreased subcutaneous and visceral fat,” first study author Joel M. Gelfand, MD, MSCE, vice chair of clinical research and medical director of the Penn Medicine Dermatology Clinical Studies Unit, director of the Psoriasis and Phototherapy Treatment Center, said in a press release. “We’re trying to untangle cardiovascular disease for this population so they can achieve better outcomes in the skin and joints, and live longer, healthier lives. This study was a proof-of-principle to better understand the impact apremilast would have on vascular disease.”

Prior research indicates that patients with a severe form of psoriasis have a higher risk of death from cardiovascular causes vs the general population. Some risk factors that are commonly linked to cardiovascular disease, such as hypertension, diabetes, obesity, and metabolic syndrome, are also prevalent in people with psoriasis.

The current study included 70 patients who were measured in changes of inflammation around the aorta, in addition to changes in body composition and 68 cardiometabolic biomarkers.

The results showed that although apremilast produced no meaningful changes in aortic inflammation, it created “variable but generally beneficial” reductions in certain biomarkers that affect cardiovascular health. Among the most notable improvements was an average 5% to 6% drop in subcutaneous and visceral fat that was observed approximately 4 months into treatment with apremilast. This continued during treatment and through the end of the study at the 1 year mark.

“Visceral fat, or fat that wraps around the abdominal organs, is of special interest because it is particularly dangerous from a cardiovascular standpoint,” Gelfand said in a press release. “It leads to problems like metabolic syndrome, cardiovascular disease, and other issues, so seeing a drop in visceral fat during apremilast treatment suggests that, over the longer term, psoriasis patients who take apremilast may be on a trajectory toward better cardiovascular health.”

The study authors said that future research into the effects of apremilast on cardiovascular health, including larger, placebo-controlled trials focusing on specific cardiovascular events. In the near future, Gelfand highlighted the need to improve screening for cardiovascular risks specifically among patients with psoriasis and psoriatic arthritis.

“Despite known associations between psoriasis and cardiovascular disease, these patients are actually less likely to get adequately screened,” Gelfand said in a press release. “And when they have risk factors identified, those factors are less likely to be adequately managed compared to their peers without psoriasis. If we can close that gap, we’ll likely be able to help individuals with psoriasis live longer and healthier lives.”

REFERENCE

Penn Research Finds Psoriasis Medication Apremilast Leads to Fat Loss in People with Psoriasis. Penn Medicine News. September 21, 2022. Accessed October 21, 2022. https://www.pennmedicine.org/news/news-releases/2022/september/medication-apremilast-leads-to-fat-loss-in-people-with-psoriasis