Background: Mirikizumab (Miri) is a humanized monoclonal antibody against the p19 subunit of interleukin (IL)-23, in patients (pts) with moderate-to-severe plaque psoriasis. Past studies showed IL-17‒producing cells remain in skin after treatment, potentially contributing to flares; though, psoriasis is clinically resolved at the biopsied sites. To determine the cellular skin milieu of pts in the current study, we evaluated the relationships between miri exposure, efficacy and skin biomarkers.
Methods: Pts (~50/group) with chronic plaque psoriasis (BSA≥10%, PASI≥12, sPGA≥3) received miri 300, 100 or 30 mg subcutaneously or placebo every 8 weeks for 16 weeks. Lesional skin biopsies from each group were assessed at baseline and Week 16 for infiltrating CD3, Treg and Th17 cells via EpiontisID™ assay, which identifies cell type‒specific epigenetic biomarkers in CpG-demethylated regions of DNA. Post-hoc analyses of fold-change over baseline and correlation coefficient between cell-type frequency and Week 16 PASI changes were conducted.
Results: Frequencies of CD3, Treg and Th17 cells at baseline were similar to previously reported values as measured by other approaches and did not correlate with PASI scores. Regardless of dose, miri significantly reduced frequencies of these T cell subsets compared to placebo (adjusted p-value for all groups <0.0003). Overall Th17 cell reduction correlated with PASI change from baseline (Spearman’s rho=0.478).
Conclusions: These results show miri’s inhibition of IL-23, a dendritic cell-derived cytokine, reduced total Th17 cells and may lead to longer periods of skin clearance without flares. To further understand the mechanism of action of miri, future translational trials are needed.

Effects on CD3, Treg and TH17 cell numbers in skin biopsies after 16-week mirikizumab treatment, evaluated by an epigenetic assay