PCSK9 inhibitors may lower risk of developing Psoriasis: JAMA.

A new 2-sample mendelian randomization study found genetic evidence that proprotein convertase subtilisin/kexin type 9 is involved in the pathogenesis of psoriasis and its inhibition may reduce psoriasis risk. The study results were published in the journal JAMA Dermatology.

Lipid-lowering drugs like statins are hypothesized to have disease-modifying properties. Previous data shows lipid pathways were implicated in the pathogenesis of psoriasis. But there are meager studies done on a large-scale and causal interpretation of results from traditional observational designs is limited by confounding. Hence researchers conducted a 2-sample mendelian randomization study from August to October 2022 to investigate the causal association between genetically proxied lipid‐lowering drugs and psoriasis risk. 

Population-level genome-wide association studies of psoriasis in the UK Biobank and FinnGen studies, and of low-density lipoprotein (LDL) by the Global Lipids Genetics Consortium were conducted. 1.3 million individuals of European ancestry participated, and Genetic association data were obtained. The inverse variance weighted method was used with pleiotropy robust methods and colocalization as sensitivity analyses. Genetically proxied inhibition of HMGCR (HMG-CoA reductase, targeted by statins), NPC1L1 (Niemann-Pick C1-Like 1, targeted by ezetimibe) and PCSK9 (proprotein convertase subtilisin/kexin type 9 targeted by, e.g., alirocumab), using LDL as the biomarker was obtained. The primary outcome was to measure the risk of psoriasis.

Results:

• Data from 12,116 psoriasis cases and ~1.3 million individuals with LDL measurement were analyzed.
• A reduced risk of psoriasis was found with Genetically proxied PCSK9 inhibition, which was replicated in FinnGen.
• There was no statistical evidence of bias from pleiotropy or genetic confounding by Sensitivity analyses.
• There was no robust association for HMGCR or NPC1L1 inhibition.

Thus, the study sets the stage for future research that may enable individuals at risk for psoriasis to select individualized lipid-lowering medications as PCSK9 may lower the risk of developing the disease.

Further reading: Zhao, SS, Yiu, ZZN, Barton, A & Bowes, J 2022, 'Lipid-lowering drugs and risk of psoriasis: a mendelian randomisation study', JAMA dermatology.