Anti-tumor necrosis factor drug responses and skin-blood DNA methylation age: Relationships in moderate-to-severe psoriasis

Studies have examined the utility of DNA methylation as a biomarker of psoriasis treatment responses, but investigations of treatment responses with Skin-Blood DNA methylation age (SkinBloodAge)—a methylation-based measure of health designed using skin tissues—are lacking. Using a HumanMethylation450 BeadChip blood DNA methylation data set from 70 white patients who presented with moderate-to-severe plaque psoriasis and were treated with anti-tumor necrosis factor (TNF) agents in Madrid, Spain, we examined the cross-sectional relationships of SkinBloodAge with anti-TNF treatment responses. Partial responders had a 7.2-year higher mean SkinBloodAge than excellent responders (P =.03). In linear regression models adjusted for chronological age, sex and anti-TNF agents - on average - partial responders had a 2.65-year higher SkinBloodAge than excellent responders (95%CI: 0.44, 4.86, P =.02). This relationship was attenuated in a sensitivity analysis adjusting for white blood cells including known T-cell mediators of psoriasis pathophysiology (β = 1.91-years, 95%CI: −0.50, 4.32, P =.12). Overall, our study suggests that partial responders to anti-TNF therapy have higher SkinBloodAges when compared to excellent responders. Although these findings still need to be confirmed more broadly, they further suggest that SkinBloodAge may be a useful treatment response biomarker that can be incorporated with other blood tests before anti-TNF therapy initiation in moderate-to-severe psoriasis patients.