Blood cytokines as potential predictors of therapy effectiveness in patients with moderate to severe psoriasis treated with the IL-12/IL-23 inhibitor ustekinumab

Background. Despite the proven efficacy and safety of biologics in the treatment of psoriasis (Ps), a number of patients experience heterogeneity in response to therapy in both the short-term and long-term perspectives.

Aims. To identify correlations between the blood cytokine levels, clinical severity indices and the effectiveness of the IL-12/IL-23 inhibitor (ustekinumab) therapy.

Methods. The study enrolled 25 patients with psoriasis. The severity of the disease was assessed using PASI, BSA, sPGA. The clinical efficacy of ustekinumab was determined by the percentage of PASI reduction: good response(≥90) moderate response (≥75) and low efficacy (≤50). Blood cytokine levels were determined by multiplex immunological analysis (xMAP) technology. Statistical analysis was performed using RStudio and the R programming language.

Results. Moderate Ps was diagnosed in 15 patients (60%), severe — in 10 (40%). The baseline levels of IL31, sCD40L and VEGF were respectively 2.3 (p = 0.018),2.3 (p = 0.010), and 2.0 (p = 0.033) times higher in severe Ps. By the 16th week, therapy was effective in 92% of patients and was accompanied by a 3.47 fold decrease in IL-31 (p = 0.002) and an increase in ICAM1 and VEGF by 35.8% (p = 0.026) and 4.2 times (p < 0.001) respectively. A correlation between ∆PASI and IL-12, IL-17F, IL-20, IL-22, IL-31, sCD40L, VEGF was found. Ustekinumab significantly modified cytokine interactions and neutralized their correlation with ∆PASI.

Conclusion. IL-31, sCD40L and VEGF baseline levels correlate with Ps severity, IL-17F, IL-20 and IL-31 — with ∆PASI, demonstrating their potential use in objectively determining Ps severity and predicting the ustekinumab therapy effectiveness.