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The following is a summary of “FC01 Higher IL-10+ T-cell and Treg-cell counts in psoriatic skin are associated with super-response to guselkumab: data from the Phase 3b GUIDE trial,” published in the December 2024 issue of Dermatology by Asadullah et al.  

The increased presence of Interleukin-10 (IL-10) and regulatory T (Treg) cells was considered to counter-regulate pathogenic tissue-resident memory (TRM) and T-helper (Th)17 cells in psoriasis.  

Researchers conducted a retrospective study to examine the clinical and immunological effect of an extended guselkumab [an interleukin (IL)-23p19 subunit inhibitor] dosing interval in patients with moderate-to-severe plaque-type psoriasis in the Phase 3b GUIDE trial (NCT03818035).  

They defined super-responders (SRes) as individuals who accomplished a psoriasis area and severity index (PASI) score of 0 at both Week 20 (W20) and Week 28 (W28) after the treatment with guselkumab. In this mechanistic substudy of GUIDE, the objective was to examine whether SRes exhibited distinct immunological differences in skin T-cell composition compared to non-SRes. Flow cytometry analysis was conducted on non-lesional skin cells at Week 0 (W0) and lesional skin cells at W0, W4, W28, and W68 from 63 participants.  

The results showed that at baseline, IL-10⁺ T-cell counts were more elevated in both non-lesional and lesional skin of  SRes compared to non-SRes, with a ratio of 3.1:1 in non-lesional skin and 3.0:1 in lesional skin (P < 0.05). This trend persisted in lesional skin after guselkumab treatment, with higher IL-10⁺ T-cell counts in SRes at Week 4 (W4) (SRe to non-SRe ratio of 4.6:1; P < 0.05) and Week 28 (W28) (ratio of 4.4:1; P < 0.05).The Treg counts (CD4⁺ CD25⁺ FoxP3⁺) were also elevated in SRes at W4 and W28, with ratios of 3.1:1 and 2.9:1, respectively (P < 0.05). Further analysis revealed that CD8⁺ TRM and IL-17A⁺ T-cell counts in lesional skin were decreased by guselkumab up to W68. The normalization of the T-cell populations in lesional skin to non-lesional skin levels occurred earlier in SRes (W28) compared to non-SRes (W68).  

Investigators concluded  the GUIDE findings suggested clinical super-response to guselkumab was linked with higher IL-10⁺ T-cell and Treg-cell counts, as well as more rapid normalization of  IL-17A⁺  and CD8⁺ TRM T-cell counts, with these counts potentially serving as predictive biomarkers for a better response in patients with moderate-to-severe plaque-type psoriasis. 

Source: academic.oup.com/bjd/article/191/Supplement_3/ljae360.001/7916111