Study Suggests PCSK9 Inhibitors May Lower Risk of Psoriasis

Lipid pathways have been implicated in the pathogenesis of psoriasis and some lipid lowering drugs are believed to have disease-modifying properties.

A recent study published in JAMA Dermatology found that PCSK9 is involved in the pathogenesis of psoriasis, and therefore, the use of PCSK9 inhibitors may lower the risk for the dermatologic condition.

According to the study, conducted by researchers from the University of Manchester, lipid pathways are likely involved in the development of plaque psoriasis. Treatments such as statins have been found to lower lipid levels, suggesting the potential for them to modify the pathogenesis of psoriasis. This prompted the investigators to evaluate the association between lipid-lowering drugs and the risk of psoriasis.

“Lipid pathways have been implicated in the pathogenesis of psoriasis, and some lipid lowering drugs, such as statins, are hypothesized to have disease modifying properties,” the study authors wrote. “However, large population level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding.”

The researchers evaluated a causal link between lipid-lowering drugs and the risk of psoriasis via a 2-sample randomization study conducted between August and October 2022. The investigators used genome-wide association data from approximately 1.3 million European patients from studies on psoriasis.

They used data from FinnGenn studies and the UK Biobank database, as well as low-density lipoprotein (LDL) data from the Global Lipids Genetics Consortium. With LDL as a biomarker, the study authors used inhibitors for Niemann-Pick C1-Like 1 (NPC1L1) targeted by ezetimibe, HMG-CoA reductase (HMGCR) targeted by statins, and PCSK9 targeted by alirocumab (Praluent).

The investigators examined data from approximately 1.3 million participants with 12,116 psoriasis cases. The data suggest that inhibiting genetically-proxied PCSK9 was associated with psoriasis risk (OR 0.69 per standard deviation reduction in LDL; 95% CI 0.55, 0.88; P = 0.003), but there was no association found for the other 2 inhibitors.

Alirocumab is indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.Alirocumab is a human monoclonal antibody that binds to PCSK9. PCSK9 attaches to the LDL receptors (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver.

The study authors were able to replicate these data through FinnGen (OR 0.71; 95%CI 0.57, 0.88; P = 0.002).

“This study provides genetic evidence that PCSK9 is implicated in psoriasis pathogenesis, and that its inhibition may reduce psoriasis risk,” the study authors wrote. “These findings pave the way for future studies that may allow personalized selection of lipid lowering drugs in those at risk of psoriasis.”

Reference

Zhao, S. S., Yiu, Z. Z. N., Barton, A., & Bowes, J. (Accepted/In press). Lipid-lowering drugs and risk of psoriasis: a mendelian randomisation studyJAMA dermatology.

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