Risankizumab influences key pathogenic Th17 cells in CD

Risankizumab, but not ustekinumab or vedolizumab, was associated with an in vivo downregulation of pathogenic Th17 cells. These cells may play an important role in Crohn’s disease (CD) pathogenesis. The authors argue that these findings may explain why risankizumab yielded better outcomes than ustekinumab in the SEQUENCE trial.

“Pathogenic memory Th17 cells are characterised by the expression of an additional surface marker, CCR5,” said Dr Daniele Noviello (University of Milan, Italy) [1]. “These pathogenic cells express higher amounts of pro-inflammatory cytokines IL-17 and IFN-γ than conventional Th17 cells. Furthermore, exposure to IL-23 was associated with the development of pathogenic Th17 cells. This evidence and other evidence indicates that these pathogenic cells play a key role in the pathogenesis of CD.”

The current study investigated how pathogenic and conventional Th17 cells responded to the biological therapies vedolizumab, ustekinumab, and risankizumab in vivo. For this purpose, the research team looked at 14 patients with CD on vedolizumab, 8 patients on ustekinumab from the SEQUENCE study, and 8 patients on risankizumab from the SEQUENCE study. “All patients were anti-TNF refractory,” added Dr Noviello.

“Pathogenic Th17 cells rarely recirculate, express tissue-resident markers, and locate into intraepithelial lymphocyte compartments,” expressed Dr Noviello. The results further showed that vedolizumab downregulates conventional Th17 cells but not pathogenic Th17 cells. Ustekinumab did not downregulate conventional or pathogenic Th17 cells. However, risankizumab was associated with a downregulation of pathogenic Th17 cells.

“The IL-23-inducible pathogenic Th17 cells have a key role in CD pathogenesis,” according to Dr Noviello. “Risankizumab, but not ustekinumab, was associated with a downregulation of pathogenic Th17 cells, potentially explaining early signs of risankizumab superiority over ustekinumab in terms of endoscopic response at week 24 in the SEQUENCE trial.”

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   1. Noviello D, et al. Risankizumab, but not ustekinumab or vedolizumab, downregulates IL-23-induced mucosal pathogenic Th17 cells in patients with Crohn’s disease. OP129, UEG Week 2024, 12–15 October, Vienna, Austria.

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Posted on 28 November 2024