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

BACKGROUND: While biologic therapies targeting interleukin-23 control cutaneous inflammation in psoriasis, their impact on epigenetic aging has not been previously demonstrated. OBJECTIVES: To evaluate the effects of tildrakizumab treatment in the epigenetic aging deviation of moderate-to severe psoriasis. METHODS: 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. RESULTS: 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). LIMITATIONS: Pilot study (small sample size). CONCLUSIONS: 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).