51成人动漫

BOSTON -- An evaluation of a common psoriasis drug's effect on one cardiometabolic risk factor instead showed a favorable impact on a different one.

The randomized trial showed that apremilast (Otezla) did not significantly affect aortic vascular inflammation but did lead to a statistically significant reduction in subcutaneous and visceral fat with no associated change in body weight. The favorable effect became apparent after about 16 weeks of treatment and persisted through week 52.

Additional studies are needed to confirm and clarify the findings, said Joel Gelfand, MD, of the University of Pennsylvania in Philadelphia, during the American Academy of Dermatology meeting.

"Apremilast had a neutral effect on vascular inflammation," said Gelfand. "Patients with a high TBR [total to background pool ratio] at baseline may experience improvements in vascular inflammation. Subcutaneous and visceral fat was reduced by 5% to 6% in apremilast patients. Apremilast had a variable but generally beneficial effects on biomarkers."

Psoriatic disease has a well recognized adverse impact on cardiometabolic risk factors, including obesity, dyslipidemia, and diabetes. Patients with psoriasis and psoriatic arthritis have an increased risk of premature cardiovascular mortality. A need exists for better understanding of psoriasis treatments' effects on cardiometabolic pathways, said Gelfand.

PET/CT of CD68-positive macrophages in fatty plaques can identify , which is increased in psoriasis and , he continued. Elevated vascular inflammation is predictive for future risk of cardiovascular events, and studies of statin therapy have shown that vascular inflammation improves within 4 to 12 weeks after starting treatment.

A series of psoriasis clinical studies evaluated the impact of different therapies on vascular inflammation and cardiovascular biomarkers. One compared adalimumab (Humira) with phototherapy and placebo. (Cosentyx) and (Stelara) were compared in separate placebo-controlled trials.

Adalimumab had the greatest impact, effecting favorable changes in multiple markers, including interleukin (IL)-6, which is causally related to cardiovascular disease, said Gelfand. Phototherapy improved C-reactive protein and IL-6 and ustekinumab reduced aortic vascular inflammation. None of the drugs improved insulin resistance.

In a continuation of the trial series, apremilast was evaluated in an involving 70 adults with moderate-to-severe psoriasis, 60 of whom had PET/CT imaging at baseline and after 16 weeks of treatment. Subsequently, 39 patients patients remained in the study to week 52, and all but one had another PET/CT scan.

The 70 patients had a mean age of 47, mean body mass index of 30, and men accounted for three-fourths of the study population. The cohort had a mean disease duration of 16 years, and eight also had psoriatic arthritis. Baseline averages for disease metrics included body surface area of 22%, psoriasis area and severity index (PASI) of 18.6, dermatology life quality index (DLQI) of 11.6, and a TBR_max of 1.61. TBR served as a marker of aortic vascular inflammation

The 16-week outcomes were consistent with apremilast's known activity in psoriasis, said Gelfand. PASI75 response was 0.35, PASI90 was 0.12, and DLQI ≤5 was 0.65. At week 52, values for the same metrics were 0.31, 0.13, and 0.67. All values were statistically improved versus baseline (P<0.001).

Neither the absolute nor percentage change in TBR differed significantly from baseline to week 16 or week 52, or from week 16 to week 52, although all of the values were reduced.

The study included CT imaging of subcutaneous and visceral adipose tissue (SAT, VAT). Analyses of that data showed statistically significant reductions in both. VAT decreased by 5.32% from baseline to week 16 (P=0.0009) and by 5.52% from baseline to week 52 (P=0.0148), with no significant change from week 16 to week 52. SAT decreased by 5.53% the first 16 weeks (P=0.0005) and by 5.50% at week 52 (P=0.0096). Values at weeks 16 and 52 did not differ significantly.

A sensitivity analysis showed that patients with a baseline TBR >1.6 had a borderline reduction at week 16 (P=0.071) and a statistically significant reduction at week 52 (P=0.005). Those with a lower baseline TBR had no significant change at 16 or 52 weeks.

An analysis of 68 blood biomarkers showed significant decreases in the inflammatory markers ferritin (P=0.015) and IL-1B (P=0.006) and a significant increase in IL-8 (P=0.08). The only changes in markers of lipid metabolism were a borderline increase in ApoA1 (P=0.05) and a decrease in HDL efflux (P=0.008). Ketone bodies, a marker of glycemia, decreased (P=0.006), whereas insulin had a borderline increase (P=0.05). Only ferritin was reduced at weeks 16 and 52, said Gelfand.

In response to a question from the audience, Gelfand said the reductions in SAT and VAT did not correlate with changes in weight.

Comment