Improving prediction of disease outcome for inflammatory bowel disease: progress through systems medicine

Figures & data

Figure 1. Difference between prognostic and predictive biomarkers.

In the past several parameters have been proposed as potential predictors of the long-term outcome and of the response to therapy in CED – in many cases these terms were used interchangeably even though prognostic and predictive biomarkers focus on two different aspects entirely. Whereas a prognostic biomarker is a marker that provides information on the likely course of the disease in an untreated individual, predictive biomarkers are defined as markers that can be used to identify subpopulations of patients who are most likely to respond to a given therapy.

Figure 2. Systems medicine approach.

Based on recent technological developments it is nowadays possible to integrate high-throughput omics (including genome and epigenome, transcriptome, proteome, metabolome, and microbiota to cite the most important aspects) with clinical datasets. Analysis of these multi-layered sets of information might open new perspective creating a circular and iterative process between clinical setting and computational pathogenetic models, allowing to develop new models for diseases prognosis and prediction of response to therapies.

Table 1. Risk factors for a more complicated disease course in Crohn’s disease and ulcerative colitis

Crohn’s disease	Ref	Ulcerative colitis	Ref
Delayed diagnosis	[58]	Delayed diagnosis	[28,44]
Black and South Asian ethnicity	[58]	Long-standing disease duration (>10 years)	[32,44]
Male gender	[58]	Male gender	[32,44]
Growth impairment at diagnosis	[50,58]	Young age at diagnosis	[32,44]
Younger age at diagnosis (higher risk for growth impairment)	[58]	Family history for IBD	[32]
Older age at diagnosis (e.g. > 13 years; higher risk for complications and for surgery)	[58]	Disease extension at diagnosis and over time	[32]
Extensive disease (pan-enteric inflammation) or deep colonic ulcers	[50]	Disease severity at diagnosis (assessed clinically through PUCAI score 65 or higher, or through endoscopy)	[32]
More active disease at diagnosis or over time	[58]	High histological inflammation score	[44]
Stricturing disease (demonstrated by endoscopic or radiological examination) at diagnosis, obstructive signs/symptoms, pre-stenotic dilatation	[50,58]	Neutrophilic inflammation of stomach and duodenum	[32]
Penetrating disease (bowel perforations, intra-abdominal fistulae, inflammatory masses, and/or abscesses at any time in the course of the disease and not as result of surgical complications)	[50,58]	Primary sclerosing cholangitis	[32]
Perianal disease	[50,58]	C. difficile infection	[32]
Small bowel disease location (higher risk of growth impairment, stricturing/penetrating complications, multiple surgeries)	[44,58]	Extra-intestinal manifestations	[24]
Ileal or ileocolonic disease location (higher risk of surgery, complications, progressive disease, disabling disease)	[44]	Elevated CRP at diagnosis	[24]
Colonic disease location (risk of permanent stoma)	[44]	Low hemoglobin (<10 g/dl) at diagnosis	[65]
No clinical remission (PCDAI > 5) 12 weeks after start of induction therapy	[50]	Low serum levels of vitamin D	[65]
No biochemical remission (CRP > 20 mg/l, fecal calprotectin > 400 µg/g) 12 weeks after start of induction therapy)	[50]	Erythrocyte sedimentation rate (ESR) ≥30 mm/h	[27]
Antibodies against OmpC (E.coli outer membrane porin C) and against CBir1 (antiflagellin)	[50,58]	Hypoalbuminemia	[32]
Antibodies against ASCA (Saccharomyces cerevisiae)	[50,58]	Frequent disease flares (> 3 per year) and frequent hospitalization	[44]
Low variety in microbiome	[59]	Steroid dependence or resistance	[44]
Presence of NOD2/CARD15 variants	[58]	PUCAI score at day 3 and at 3 months	[29,32]
Smoking	[44]	Antibodies against ASCA (Saccharomyces cerevisiae) and ANCA (antineutrophil cytoplasmic antibodies)	[32]
		Low variety in microbiome	[59]
		No smoking	[44]

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