Multi-Omics Biomarkers for Predicting Efficacy of Biologic and Small-Molecule Therapies in Adults With Inflammatory Bowel Disease: A Systematic Review

Abstract

The heterogeneity and suboptimal efficacy of biological treatments and small molecule drugs necessitate their precise selection based on biomarkers that predict therapeutic responses in inflammatory bowel disease. Recent studies have identified numerous novel biomarkers predictive of responses to biologics and small molecule modulators, utilizing a variety of omics approaches in inflammatory bowel disease. In this review, we systematically examine baseline omics biomarkers that predict responses to biological therapies and small molecule drugs, drawing on literature from PubMed. Our analysis spans multiple omics disciplines, including genomics, transcriptomics (both bulk RNA and single-cell RNA sequencing), proteomics, microbiomics, and metabolomics, with particular emphasis on the impact of models integrating multiple omics datasets. Additionally, to further the field of precision medicine, we evaluated specific biomarkers that may exhibit distinct effects on responses to multiple therapeutic interventions.

Keywords: Crohn's disease; adalimumab; certolizumab; inflammatory bowel disease; infliximab; precision medicine; tofacitinib; ulcerative colitis; ustekinumab; vedolizumab.

FIGURE 1

Predicting the response to biologics and small molecule drugs using multi‐omics baseline biomarkers, including genomics, transcriptomics, proteomics, microbiome, and metabolomics. The quantity of articles pertaining to each drug class, along with the representative biomarkers for each omic category within each drug class, is presented. The words highlighted in red denote biomarkers that have demonstrated predictive utility for the efficacy of various drugs concurrently.

FIGURE 2

Biomarkers that have shown predictive utility for the efficacy of various drugs concurrently and may facilitate the precise selection of therapeutic agents in future clinical applications. The correlation between these biomarkers and the efficacy of each drug is represented through distinct color coding. CD, Crohn's disease; GIMATS module, a cellular module consisting of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells; IBD, inflammatory bowel disease.