Current approaches to disease severity and therapy effectiveness assessment in patients with inflammatory bowel disease

Table 1 Endpoints for measuring disease modification and disease progression prevention according to the SPIRIT consensus[43]

Disease stage	Disease impact, measuring tools and timing
Early impact on health-related quality of patient’s life (patient-reported)	Health-related quality of life
	Tools: Questionnaires IBDQ-36 and SF-36
	Disability
	Tool: IBD disability index
	Fecal incontinence
	Tool: Jorge and Wexner (Cleveland) score
	Time point: 6-12 months
Mid-term complications	Bowel damage in CD
	Tool: Lémann index
	Time point: 12-24 months
	IBD-related surgery
	Tool for UC: Any colectomy
	Tools for CD: CD-related surgery; endoscopic balloon dilation; perianal surgery
	Time point: 24-36 months
	IBD-related hospitalizations
	Tool: Number of hospitalizations + cumulative hospital length of stay
	Time point: 12-24 months
	Disease extension in UC
	Tool: Macroscopic proximal disease extension (excluding pancolitis patients)
	Time point: 2-5 years
	Extraintestinal manifestations (all considered together)
	Time point: 12-36 months
	Permanent stoma
	Short bowel syndrome
Long-term complications	Dysplasia or cancer (all considered together)
	Time point: 5 years
	Mortality
	Tool: Both IBD-related and non-IBD-related mortality
	Time point: 5 years

IBDQ-36: The 36-item inflammatory bowel disease questionnaire; SF 36: Short form-36 health survey; IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis.

Table 2 Endoscopic techniques used for inflammatory bowel disease detection and monitoring

Endoscopic technique	Technique versions	Main advantages	Main disadvantages
Standard white light endoscopy		Widely used, regarded as the easiest option, being the standard endoscopy technique. Short examination time. This is a relatively low-cost option	Not always reflects histopathological IBD activity. Does not allow microvascular characterization
Chromoendoscopy	Dye-based chromoendoscopy)	Enhances mucosal visualization using dyes	Poorly studied in the context of IBD
	Virtual electronic chromoendoscopy	Employs optical filters and digital programs to improve visualization of glandular patterns and vascularization. Correlates with histopathological IBD activity. Short examination time. This is a widely available and relatively low-cost option	Highly trained personnel needed for applying currently available scores. Requires more prognostic validation
Optical magnification (high definition) endoscopy		Magnification adjustment allows maintaining image quality even at high zoom levels. The technique is easy to use. This is a relatively low-cost option	Does not permit efficiently examining the whole colonic surface
Ultra magnification endoscopy	Confocal laser endomicroscopy	Integrating laser scanning microscopy into an endoscope provides high-resolution histopathological imaging in vivo and allows intestinal barrier assessment	These techniques do not permit efficiently examining the whole colonic surface. Long duration of the examination. Highly trained personnel needed
	Endocytoscopy	The ultra-high magnification combined with the use of a mucolytic agent enhancing the penetration of a topical contrast agent provides highly accurate images in vivo. Intestinal barrier assessment possible
	Fluorescence molecular endoscopy	Targeted fluorescent probes permit to enhance the contrast between normal and diseased tissue
	Near-infrared fluorescence imaging	The use of near-infrared probes allows achieving deeper tissue penetration and improve signal-to-background ratio

IBD: Inflammatory bowel disease.

Table 3 Serum and fecal biomarkers investigated in the context of inflammatory bowel disease according to recent publications[46,116,117,121,122]

Serum biomarkers	Fecal (or colorectal mucus) biomarkers
C-reactive protein1	Fecal calprotectin
Angiopoietin 11	Fecal lactoferrin
Angiopoietin 21	Fecal protein S100A12
Serum amyloid A11	Fecal protein - high mobility group 1
Interleukin 71	Neopterin
Extracellular matrix metalloproteinase inducer1	Polymorphonuclear neutrophil elastase
Matrix metalloproteinase 11	Fecal hemoglobin
Matrix metalloproteinase 21	α1-antitrypsin
Matrix metalloproteinase 31	Human neutrophil peptides
Matrix metalloproteinase 91	Neutrophil gelatinase-associated lipocalin
Transforming growth factor α1	Chitinase 3-like-1
Carcinoembryonic antigen-related cell adhesion molecule 11	Matrix metalloproteinase 9
Vascular cell adhesion molecule 11	Lysozyme
Serum calprotectin	M2-pyruvate kinase
Serum protein S100A12	Myeloperoxidase
Neopterin	Eosinophil cationic protein
Endothelin	Human β-defensin 2
Interleukin-6, interleukin-8, interleukin-17	β-glucuronidase
Soluble tumor necrosis factor receptor 1	Osteoprotegerin
Soluble interleukin-2 receptor	Lipocalin-2/neutrophil gelatinase-associated lipocalin
Perinuclear anti-neutrophil cytoplasmic antibodies	Colorectal mucus calprotectin
Anti-Saccharomyces cerevisiae antibodies	Colorectal mucus eosinophil-derived neurotoxin
Anti-mannobioside carbohydrate antibodies	MicroRNAs (MiR-16, MiR-21, MiR-223, MiR-1246)
Anti-laminaribioside carbohydrate antibodies
Anti-chitobioside carbohydrate antibodies
Anti-laminarin antibodies
Anti-chitin antibodies
Anti-flagellin CBir1 antibodies
Antibodies against the outer-membrane porin C of Escherichia coli
Antibodies against a Pseudomonas fluorescence-associated sequence l2
Serum leucine-rich glycoprotein
Micro RNAs (MiR-16, MiR-21, MiR-155, MiR-223, MiR-320a)

¹Components of Endoscopic Healing Index[118].