The Effects of Tildrakizumab in the Epigenetic Aging Deviation of Psoriasis: A 52-Week Open-Label Study.

Abstract

While biologic therapies targeting interleukin-23 control cutaneous inflammation in psoriasis, their impact on epigenetic aging has not been previously demonstrated. To evaluate the effects of tildrakizumab treatment in the epigenetic aging deviation of moderate-to severe psoriasis. In an open-label 52-week clinical trial, 20 adults with psoriasis were treated with tildrakizumab-asmn 100 mg injections until week 28. Ten age-matched controls without psoriasis were enrolled. Genome-wide DNA methylation (DNAm) was profiled in peripheral blood leukocyte DNA (MethylationEPICv2.0, Illumina) to calculate epigenetic aging clocks predictive of all-cause-mortality, phenotypic age, chronological age, pace of aging, and telomere length. Epigenetic age deviation was calculated as the residuals against chronological age. Psoriasis patients had increased epigenetic age deviation in clocks predictive of mortality: PCGrimAge (P=0.008), CpGPTPCGrimAge3 (P=0.019), CpGPTGrimAge3 (P=0.019), GrimAge2 (P=0.049). PCGrimAge was reversed by 0.3 years (week 28, P=0.005) and 0.5 years (week 52, P=0.04) after the use of tildrakizumab-asmn. The pace of aging was increased in psoriasis patients: DunedinPACE (P=0.049). Pilot study (small sample size). Psoriasis patients presented accelerates epigenetic aging in mortality-predictive clocks. Treatment with tildrakizumab-asmn (IL-23 inhibition) showed partial reversal of those clocks in 28 weeks. (Funded by Sun Pharmaceutical Industries, Inc; ClinicalTrials.gov number, NCT05110313).