Search in the Abstract Database

Abstracts Search 2019

P315 Systemic and tissue modulation of IL-23 pathway biomarkers in a Phase 2 study of risankizumab in patients with Crohn’s disease

A. Salas*1, K. M. Grebe2, N. Powell3, J. Panés1, J. W. Davis4, F. Hong4, Y. Pang4, A. A. Suleiman5, K. Wallace4, B. G. Feagan6

1Hospital Clinic Barcelona, Barcelona, Spain, 2AbbVie Inc., Worcester MA, USA, 3Guy's and St Thomas' Hospital, London, UK, 4AbbVie Inc., Chicago, IL, USA, 5AbbVie Inc., Ludwigshafen am Rhein, Germany, 6University of Western Ontario, London, ON, Canada


Risankizumab, a humanised monoclonal antibody that specifically targets the p19 subunit of interleukin (IL)-23, is currently under evaluation in Crohn’s disease (CD) and other inflammatory diseases. This biomarker study aimed to provide mechanistic insights on risankizumab in patients with active CD.


We evaluated data from a randomised, double-blind, placebo (PBO)-controlled Phase 2b induction study in patients with moderate-to-severe CD (NCT02031276) who received intravenous risankizumab (200 or 600 mg), or PBO at Weeks 0, 4, and 8. At baseline (BL) and Week 12, IL-23 pathway biomarkers and other biomarkers of inflammation were measured as protein (from plasma) or by RNA sequencing (RNAseq) (from colon or ileum tissue biopsies). In addition, we assessed potential correlations between BL IL-22 or reduction in IL-22 from BL and Week 12 clinical response following risankizumab treatment.


Plasma and colon RNA data were available for 22–35 patients in each of the three treatment groups (Table 1). At Week 12, statistically greater reductions (%) from BL in risankizumab-treated vs. PBO-treated patients were observed for plasma biomarkers (IL-17, IL-1b, IL-22, C-reactive protein, calprotectin, and lactoferrin) and colon RNA biomarkers (IL-17A, IL-1b and IL-23A). Comparisons between risankizumab and PBO treatments groups were significant for the majority of plasma and RNA endpoints; comparisons between risankizumab dose groups (200 vs. 600 mg) were not significant with the exception of calprotectin. KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathway analysis of RNA signatures demonstrated perturbation of the IL-17 signalling pathway and other inflammation signatures by risankizumab 600 mg. Neither BL IL-22 levels nor IL-22 reduction from BL following risankizumab treatment was predictive of the clinical efficacy at Week 12.


Risankizumab treatment in patients with active CD led to greater reductions in IL-23 pathway and other inflammation biomarkers compared with PBO, as measured in both plasma and tissue biopsies. IL-22 plasma levels at BL or reduction in IL-22 following risankizumab treatment were not predictive of response to risankizumab.

Table 1. Plasma and RNAseq biomarker changes at Week 12.