Study Suggests PCSK9 Inhibitors May Reduce Psoriasis Risk

Sizheng Steven Zhao, MBChB, MRCP

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is implicated in the pathogenesis of psoriasis, and PCSK9 inhibitors may decrease the risk of psoriasis, according to new research.

In the development of plaque psoriasis, lipid pathways are believed to be involved. Treatments like statins that are known to decrease lipid levels are hypothesized to modify the disease, and this association between lipid-lowering drugs and risk of psoriasis is why the study was conducted.

The study was led by Sizheng Steven Zhao, MBChB, MRCP, from the Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Science, at the School of Biological Sciences at the University of Manchester.

“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,” Zhao and colleagues wrote. “However, large population level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding.”

Background

The investigators assessed the causal link between lipid-lowering drugs and psoriasis risk for patients by using a 2-sample randomization study conducted in the timeframe of August of 2022 to October of 2022.

The research team used the genetic association data of approximately 1.3 million European patients, using genome-wide association studies on psoriasis.

They accessed psoriasis information from the FinnGenn studies as well as the UK Biobank database, in addition to accessing low-density lipoprotein (LDL) information from the Global Lipids Genetics Consortium.

Utilizing LDL as a biomarker, the investigators used inhibitors for the following: Niemann-Pick C1-Like 1 (NPC1L1) targeted by ezetimibe, HMG-CoA reductase (HMGCR) targeted by statins, and PCSK9 targeted by alirocumab.

Findings

The study examined data from around 1.3 million participants and 12,116 cases of psoriasis, and the results indicated that inhibition of genetically-proxied PCSK9 had an association with psoriasis risk (OR 0.69 per standard deviation reduction in LDL; 95%CI 0.55, 0.88; P = 0.003), with no association found for the other 2 inhibitors.

Additionally, the investigators were able to replicate this 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,” they wrote. “These findings pave the way for future studies that may allow personalized selection of lipid lowering drugs in those at risk of psoriasis.”

The study, “Lipid-lowering drugs and risk of psoriasis: a mendelian randomisation study,” was published online by the University of Manchester.