The trial, led by Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania, Philadelphia, found that apremilast (Otezla) has a neutral effect on aortic vascular inflammation in patients with moderate to severe psoriasis.
It also had variable, but generally favorable, associations with 68 cardiometabolic biomarkers tested and associations with reductions in both visceral and subcutaneous fat. Findings of the study were published online in JAMA Dermatology.
Fat reductions maintained at 1-year mark
The researchers found a 5%-6% reduction in subcutaneous and visceral fat at week 16 of the study that was maintained at the 1-year mark. “The fact that it was rock stable a year later is pretty encouraging,” Dr. Gelfand told this news organization.
As for effects on vascular inflammation, Dr. Gelfand said, “The good news is we didn’t find any adverse effects on aortic vascular inflammation, but we didn’t find any beneficial effects either. That was a little disappointing.
“The most surprising thing was really the effects on visceral adiposity,” he added. “I’m not aware of any other drug having demonstrated that effect.”
Michael S. Garshick, MD, a cardiologist with NYU Langone Health in New York, who was not involved with the trial, told this news organization that despite seemingly good epidemiologic evidence in observational studies that by treating psoriasis surrogates of cardiovascular risk can be reduced, this trial, like others before it, failed to reduce aortic vascular inflammation.
The trial does help answer the question of whether apremilast can induce weight loss, he said, something that earlier trials suggested. “This trial confirms that, which is exciting,” he said. The reduction in both visceral and subcutaneous fat “deserves a lot further study.”
Several questions remain, Dr. Garshick said. Both he and Dr. Gelfand pointed to the need for large, placebo-controlled trials. “We still don’t know which medications may be preferrable in psoriasis to reduce [cardiovascular] risk if any at all,” Dr. Garshick said.
Seventy patients enrolled
In total, 70 patients with moderate to severe psoriasis were enrolled, 60 completed week 16, and 39 completed week 52 of the single-arm, open-label trial conducted between April 2017 and August 2021 at seven dermatology sites in the United States.
Participants took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily. Participants’ average age was 47.5 years; most were male (77.1%) and White (82.9%); almost 6% were Black. Average body mass index was 30 kg/m2. Patients could not have received biologics within 90 days of study baseline (or 180 days for ustekinumab [Stelara]).
There was no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% confidence interval [CI], −0.08 to 0.05; P = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; P = .09) compared with baseline.
“At week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine,” the authors wrote, adding that at week 52, compared with baseline, “there were reductions in levels of ferritin, cholesterol efflux capacity, beta-hydroxybutyrate, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.”
This study highlights the importance of screening, Dr. Garshick said.
He and Dr. Gelfand said people with psoriatic disease tend to be vastly underscreened for cardiovascular risk factors.
Dr. Gelfand said, “If we did what we knew worked – meaning we screened them for diabetes, we screen their cholesterol, we check their blood pressure, and we adequately treated those traditional cardiovascular risk factors, we probably could narrow the gap quite a bit” in terms of the lower life expectancy people face when they have more significant psoriasis.
Celgene was the initial funding sponsor; sponsorship was then transferred to Amgen. The authors designed, executed, analyzed, and reported the study. Celgene provided nonbinding input into study design, and Amgen provided nonbinding input into the reporting of results. Dr. Gelfand reported numerous disclosures with various pharmaceutical companies and organizations. Dr. Garshick reported no relevant financial relationships.
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