Examining Molecular, Histopathologic Changes With Risankizumab vs Ustekinumab in Psoriasis

Interleukin 23
Interleukin 23
Investigators observed differences and similarities in molecular and histopathologic profiles in skin lesions of patients with psoriasis treated with risankizumab vs ustekinumab.

In patients with psoriasis, treatment with risankizumab is associated with changes in the molecular and histopathologic profiles of lesional skin after 4 weeks compared with ustekinumab, according to study results published in The Journal of Allergy and Clinical Immunology.

The investigators used the results of 2 studies – a phase 1 single-rising-dose study of risankizumab therapy (ClinicalTrials.gov identifier: NCT01577550) and a phase 2 study of risankizumab vs ustekinumab (ClinicalTrials.gov identifier: NCT02054481) –  to explore the similarities and differences in the histopathologic and molecular profiles of skin lesions from patients with psoriasis who had been treated with risankizumab or ustekinumab. Lesional skin biopsies obtained from patients with moderate to severe plaque psoriasis who had participated in the phase 1 (n=39) and phase 2 (n=60) studies were analyzed by histopathology, RNA-sequencing, and immunochemistry.

Results showed that treatment with risankizumab generated a rapid decrease in protein and transcriptomic biomarkers associated with the interleukin-23 (IL-23) pathway, with these reductions maintained through 8 weeks. At week 4, risankizumab decreased histopathologic biomarker expression, including K16, Ki67, CD3, CD11c, DC-LAMP, lipocalin-2, β-defensin 2, and S100A7.

Based on global histopathology scoring, 54% and 69% of patients who were treated with risankizumab 90 mg or risankizumab 180 mg, respectively, were graded as “excellent improvement,” compared with 29% of patients treated with ustekinumab. At 4 weeks, a common decrease in 2645 genes expressed in lesional skin was reported between risankizumab and ustekinumab, with a significant reduction observed in 2682 genes that are unique to risankizumab therapy.

Cytokine-induced transcriptome changes in key cell lines linked to psoriatic skin lesions— epidermal cells, keratinocytes, and monocytes—demonstrated a greater reduction in expression with risankizumab treatment compared with ustekinumab therapy.

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The investigators concluded that the key pathways and types of cells identified in this study may help build hypotheses for the observed differences in efficacy reported according to biologic agent. Additional studies are warranted in order to further characterize the profile of risankizumab and compare the agent with ustekinumab and other biologics, thus enabling an improved understanding of the relationship of these agents to longer-term efficacy and the potential remission of psoriasis.

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Visvanathan S, Baum P, Vinisko R, et al. Psoriatic skin molecular and histopathological profiles following treatment with risankizumab versus ustekinumab [published online December 19, 2018]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2018.11.042