587 Higher IL-10+ T cell and treg cell counts in psoriatic skin are associated with super-response to guselkumab: Data from the phase 3 guide trial

Interleukin-10 (IL-10) and regulatory T (Treg) cells are immunosuppressive mediators with key roles in autoimmunity. Their increased presence is believed to counter-regulate pathogenic tissue resident memory (TRM) and Th17 cells in psoriasis (PSO). The GUIDE study (NCTO3818035) aimed to determine if guselkumab (GUS)-treated plaque-PSO patients who achieved ‘super-response’ (SRe; PASI=0 at Week [W] 20 and W28) show immunological differences in skin T cell composition versus non-SRe (nSRe) based on flow cytometry analysis of non-lesional (NL; W0) and lesional (L; W0, 4, 28, 68) skin cells (63 patients). IL-10+ T cell counts were higher in both NL and L skin at baseline in SRe versus nSRe (SRe to nSRe ratio of 3.1:1 and 3.0:1, respectively, P<0.05). This trend was maintained in L skin after GUS treatment, with higher IL-10+ T cell counts seen in SRe at W4 and W28 (SRe to nSRe ratio of 4.6:1 and 4.4:1 respectively; P<0.05). Also, Treg cell (CD4+CD25+FoxP3+) counts were higher in SRe at W4 and W28 (SRe to nSRe ratio of 3.1:1 and 2.9:1 respectively, P<0.05). Further analysis of effector T cell subsets showed that CD8+ TRM and IL-17A+ T cell counts in L skin were reduced by GUS up to W68. Normalization of these T cell populations in L skin to NL skin levels appeared to be earlier in SRe (W28) than nSRe (W68). These results suggest clinical super-response may be characterized by higher IL-10+ T cell and Treg cell counts, and faster normalization of CD8+ TRM and IL-17A+ T cell counts. Thus, higher IL-10+T cell and Treg cell counts may be predictive biomarkers for better response to GUS in PSO.