We all know that psoriasis is more than just a disease of the skin as it involves various comorbidities, including cardiometabolic disease. National guidelines indicate that dermatologists should screen for cardiometabolic disease and that adequate treatment of cardiometabolic disease and risk factors is provided accordingly. An important question, however, remains to be answered: what is the effect of available systemic treatments for psoriasis on the components of cardiovascular disease? So far, our knowledge of the impact of various anti-psoriatic treatments on cardiovascular disease and cardiovascular disease risk factors is fragmentary. Recently, a study was conducted on the effect of apremilast on vascular inflammation and cardiometabolic functions¹ with an impressively comprehensive set of markers for vascular inflammation and cardiometabolic disease.

Adult patients with chronic plaque psoriasis over at least 10% of body surface area were enrolled in a clinical trial on the effect of apremilast on cardiometabolic disease. After a screening period (≤4 weeks), an open-label treatment period of 52 weeks followed. Apremilast was given per US Food and Drug Administration-approved dosing regimen. At baseline and after 16 and 52 weeks, aortic vascular inflammation was assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Furthermore, changes in inflammatory-, lipid -, and metabolic biomarker levels were assessed between baseline and weeks 16 and 52. Adipose tissue volumes at L2 to L3 were simultaneously measured using automated in-house software assessments. Compared with baseline, no change in aortic vascular inflammation was observed at week 16 or week 52. At week 16, potentially beneficial decreases in interleukin 1b, valine, leucine, isoleucine, fetuin-A, and branched-chain amino acids were observed in the blood. At week 52, compared with baseline, potentially beneficial decreases in ferritin, β-hydroxybutyrate, acetone, and ketone bodies, with an increase in apolipoprotein A-1, were observed in the blood. Still, there was a reduction in cholesterol efflux. Approximately 5% to 6% reduction in subcutaneous and visceral adiposity at week 16 was maintained at week 52. The overall conclusion from this study was that apremilast did not improve vascular inflammation but is associated with beneficial changes in blood cardiometabolic biomarkers.

The markers evaluated in this study are surrogate markers for cardiometabolic disease. The study, therefore, suggests a potential beneficial effect of apremilast on this comorbidity. However, an effect of apremilast on the actual prevention of the occurrence of cardiovascular comorbidity remains to be shown. Intriguingly, significant reductions in visceral and subcutaneous fat were observed. It has been excluded that this effect results from nausea,^2,3 a well-known adverse effect of apremilast. It has been previously suggested that the effect of apremilast on visceral obesity is directly mediated by enhanced glucagon-like peptide-1 (GLP-1) activity.⁴ Therefore, longer-term studies on the effect of apremilast on cardiovascular disease itself seem to be worthwhile.

Is apremilast unique in interfering with cardiometabolic markers? Various biologics used to treat psoriasis influence vascular inflammation and cardiometabolic parameters, thereby reducing cardiovascular risk.^5-8 Furthermore, methotrexate, cyclosporine, and tofacitinib have been suggested to impact vascular inflammation and biomarkers of cardiometabolic disease in psoriatic patients.⁹

Should we wait for evidence from long-term controlled studies before taking advantage of the daily practice of these new compelling insights revealed by surrogate markers for cardiovascular disease? In a learning healthcare environment, we can treat our patients while capturing real-world evidence on the effect of the anti-psoriatic treatments on cardiometabolic risk factors and cardiovascular disease in patient registries, not only from the point of view of pharmacovigilance but from the point of view of a more holistic disease severity assessment, which is more than skin deep, considering cardiovascular risk and comorbidity.