Precision medicine in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is an incurable disease characterized by remission-relapse cycles throughout its course. Both Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of IBD, exhibit tendency to develop complications and substantial heterogeneity in terms of frequency and severity of relapse, thus posing great challenges to the clinical management for IBD. Current treatment strategies are effective in different ways in induction and maintenance therapies for IBD. Recent advances in studies of genetics, pharmacogenetics, proteomics and microbiome provide a strong driving force for identifying molecular markers of prognosis and treatment response, which should help clinicians manage IBD patients more effectively, and then, improve clinical outcomes and reduce treatment costs of patients. In this review, we summarize and discuss precision medicine in IBD, focusing on predictive markers of disease course and treatment response, and monitoring indices during therapeutic drug monitoring.

Keywords: disease course; inflammatory bowel disease; precision monitoring; precision treatment; treatment response.

Figure 1.

Precision medicine in IBD. Based on risk stratification by analyzing the determinants of disease course and treatment response including clinical, genetic, epigenetic, serological and fecal markers, physicians then select a targeted therapy and apply precision monitoring for individual patient. IBD: inflammatory bowel disease.

Figure 2.

The metabolic pathways of azathioprine. Azathioprine changes into 6-mercaptopurine after absorption by the GI tract. 6-mercaptopurine can then be metabolized through three competing pathways: conversion into 6-TIMP by HGPRT; methylation by TPMT into 6-MMP; and conversion into 6-TU by XO. 6-TIMP can then be successively metabolized into 6-TXMP and 6-TGNs by IMPDH and GMPS, respectively. GST: glutathione s-transferase; 6-MP: 6-mercaptopurine; TPMT: thiopurine s-methyltransferase; 6-MMP: 6-methylmercaptopurine; XO: xanthine oxidase; 6-TU: 6-thiouric acid; HGPRT: hypoxanthine–guanine phosphoribosyl transferase; 6-TIMP: 6-thioinosine monophosphate; MPK: monophosphate kinase; 6-TIDP: 6-thioinosine diphosphate; DPK: diphosphate kinase; 6-TITP: 6-thioinosine triphosphate; 6-MeTITP: 6-methylthioinosine triphosphate; ITPA: inosine triphosphate pyrophosphatase; IMPDH: inosine monophosphate dehydrogenase; 6-TXMP: 6-thioxanthosine 5’-monophosphate; GMPS: guanosine monophosphate synthetase; 6-TGMP: 6-thioguanine monophosphate; 6-TGDP: 6-thioguanine diphosphate; 6-TGTP: 6-thioguanine triphosphate; NUDT15: nudix hydrolase 15; 6-TGNs: 6-thioguanine nucleotides; 6-MeTGMP: 6-methythioguanine monophosphate.