In a study, researchers investigated the effects of genetically proxied TYK2 inhibition on various disease outcomes and biomarkers. The researchers used a specific genetic variant in the TYK2 gene as a proxy for TYK2 inhibition and conducted a phenome-wide Mendelian randomization (MR) study using data from the UK Biobank and FinnGen. They also performed additional analyses, including tissue-specific gene expression MR, colocalization analyses, and MR with blood biomarkers. A systematic review of randomized controlled trials on TYK2 inhibitors was conducted as well.
The findings of the study suggest that genetically-proxied TYK2 inhibition is associated with a reduced risk of autoimmune diseases such as hypothyroidism, psoriasis, systemic lupus erythematosus, and rheumatoid arthritis. However, there were nominal associations of TYK2 inhibition with an increased risk of prostate and breast cancer. Researchers concluded that TYK2 inhibitors may have therapeutic potential for psoriasis and other autoimmune diseases, but close monitoring of potential adverse effects is necessary.
Reference: Yuan S, Wang L, Zhang H, et al. Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases. EBioMedicine. 2023;89:104488. doi: 10.1016/j.ebiom.2023.104488.