Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review

Table 3 Synthetic presentation of data on combined marker performance in detecting mucosal healing

Ref.	Study type	Investigated marker	MH definition	CU/CD	Number of patients	AUC	95%CI	Sn (%)	Sp (%)	Cutoff level
Reinisch et al[43]	Post hoc analysis of clinical trial	FC, CRP and CDAI	CDEIS < 4	CD	244	0.68,	0.62-0.74	74	64	FC < 250 mcg/g, CRP < 5 mg/L, and CDAI < 150
D'Haens et al[41]	Prospective-specimen collection, retrospective–blinded-evaluation	EHI	SES-CD of ≤ 2 and ≤ 1 in each segment	CD	311 in 2 cohorts (116 + 195)	0.962; 0.693	0.942-0.982; 0.619-0.767	97.1; 83.2 (for cutoff of 20)	100; 87.8 (cutoff of 50)	≤ 20
Gubatan et al[42]	Prospective cohort	IL-4 + IL-10/IL-17A + TNF-α	Geboes Histologic Grade of < 3	CU	70	0.641		52.6	75	0.1522
Mavropoulou et al[44]	Prospective cohort	sIL-2R (CU); IL-6 (CD); FC (UC); FC (CD)	MES = 0-1; SES-CD ≤ 3	UC + CD	299 (84 + 145)	0.80; 0.80; 0.92; 0.84	0.68-0.91; 0.71-0.89; 0.86-0.99; 0.76-0.92	63; 69; 91; 70	85; 80; 89; 100	< 646 IU/mL; < 5.5 pg/mL; 340 mg/kg; < 180 mg/kg

EHI: Endoscopic healing index measuring 13 proteins in blood [angiopoietin 1 (ANG1) and 2 (ANG2), carcinoembryonic antigen-related cell adhesion molecule 1, C-reactive protein, serum amyloid A1, interleukin 7, transforming growth factor α, vascular cell adhesion molecule 1, extracellular matrix metalloproteinase inducer, and matrix metalloproteinases 1 (MMP1), 2 (MMP2), 3 (MMP3), and 9 (MMP9)]; UC: Ulcerative colitis; CD: Crohn’s disease; AUC: Area under the curve; CI: Confidence interval; Sn: Sensitivity; Sp: Specificity; SES-CD: Simple endoscopic score for Crohn’s disease; CRP: C-reactive protein; CDAI: Crohn’s disease activity index; sIL-2R: Soluble interleukin 2 receptor; MES: Mayo endoscopic subscore; FC: Fecal calprotectin.