The Role of Vedolizumab in Combination Therapy for Treating Ulcerative Colitis with Non-response
ZHANG Shuai
WU Yinong
GUO Lianyi
LIU Baohai
Abstract：Objective To identify the precise molecular targets for vedolizumab(VDZ)treatment of ulcerative colitis(UC)that lead to non-response through clinical multivariate analysis and machine learning,and to explore combined medication strategies.Methods A retrospective study was conducted to analyze the risk factors related to the clinical response of patients with moderate to severe ulcerative colitis(UC)who received VDZ treatment,and a Logistic regression analysis was constructed.At the same time,based on the comprehensive dataset of gene expression,differential gene expression analysis,weighted gene co-expression network analysis,protein interaction network,and least absolute shrinkage and selection operator regression analysis were used to screen the key genes for non-response.Combined with immune infiltration analysis and the Enrichr website,potential combined therapeutic drugs were explored.Results Clinical multivariate analysis revealed that a Mayo endoscopy score of≥2 points was an independent risk factor for clinical response(OR=5.835,95%CI:1.052-32.361,P=0.044).Bioinformatics analysis and machine learning identified interferon regulatory factor 4(IRF4)as the core hub gene driving the failure to respond.Functional enrichment analysis indicated that it was mainly enriched in key pathways such as the differentiation of type 17 helper T cells(Th17)and the interleukin 17(IL-17)signaling pathway.Immune infiltration analysis showed that M1 macrophages and neutrophils were significantly enriched in patients with failure to respond,suggesting the activation of alternative inflammatory pathways.Based on these mechanisms,JAK inhibitors and anti-interleukin 23(IL-23)antibodies were selected as potential combined treatment strategies to reverse the failure to respond in VDZ.Conclusion A Mayo endoscopy score of≥2 points is an independent risk factor for the clinical response in patients undergoing VDZ treatment.For UC patients with severe endoscopic inflammation,the failure to respond to VDZ may be related to the activation of the alternative inflammatory pathway mediated by the IRF4 gene.The combined use of JAK inhibitors or anti-IL-23 antibodies may be an effective strategy to overcome this challenge.
Keywords：vedolizumabulcerative colitisnon-responsecombination medication
Publication Date：2026-02-28
Online Publishing Date：2026-03-20(First online date of this platform, not the publication date of the document)
Pages：8( 87-94 )