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

Table 1 Synthetic presentation of data on fecal 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
E Penna et al[22]	Prospective cohort	FC	SES-CD ≤ 2	CD	65 + 21 individuals in the control group	0.77	0.65-0.88	96	78	155 mcg/g
Hiraoka et al[17]	Prospective cohort	FC	MES = 0	UC	84	0.67	0.56 - 0.78	77	67	180 mcg/g
Hiraoka et al[17]	Prospective cohort	FIT	MES = 0	UC	84	0.62	0.50- 0.74	95	62	NA
Lee et al[23]	Prospective cohort	FC-ELISA; FC-QPOCT	MES = 0; SES-CD < 4	UC + CD	93	0.88	NANA	81.8(ELISA); 85.7 (QPOCT)	100 ELISA; 100 QPOCT	201 mcg/g ELISA; 150.5 mcg/g QPOCT
Urushikubo et al[24]	Cross-sectional, observational	FC	MES = 0; REI = 0; UCEIS = 0	UC	50	0.823; 0.780; 0.777	0.707-0.939; 0.658-0.903; 0.645-0.909	100; 100; 88	62; 70; 71	490 mcg/g; 288 mcg/g; 288 mcg/g
Ryu et al[18]	Retrospective cohort	FIT	MES = 0; UCEIS = 0-1	UC	128	NA	NA	98.0; 94.9	37.4; 38.3	100 ng/mL
Ryu et al[18]	Retrospective cohort	FC	MES = 0; UCEIS = 0-1	UC	128	NA	NA	78.4; 74.6	74.4; 76.5	170 mcg/g
Lin et al[25]	Multicentric prospective cohort	FC	UCEIS < 3; CDEIS < 6	UC + CD	88	0.87; 0.74	NA	88; 50	75; 100	191 mcg/g; 918 mcg/g
Vázquez Morón et al[26]	Prospective cohort	FC	SES-CD ≤ 2	CD	71	NA	NA	95.9	52.3	71 mcg/g
Ryu et al[27]	Retrospective cohort	FIT	MES = 0-1	UC	63	0.81	0.59-0.94	73.33	81.82	< 7 ng/mL
Hassan et al[28]	Prospective cohort	FC	MES = 0-1	UC	44	0.949	0.838-0.992	89.7	93.3	58 mcg/g
Kostas et al[29]	Retrospective cohort	FC	MES = 0-1; absence of mucosal lesions for CD	UC + CD	149	0.956	NA	91.9	87.2	174 mcg/g
Yen et al[21]	Retrospective cohort	FC	MES = 0-1	UC	50	0.812	NA	74.19	84.21	156 mcg/g
Yen et al[21]	Retrospective cohort	iFOBT	MES = 0-1	UC	50	0.906	NA	80.65	100	≤ 43 ng/mL
Kristensen et al[30]	Prospective cohort	FC	MES = 0-1	UC	20	NA	NA	82.4	100	250 mcg/g

UC: Ulcerative colitis; CD: Crohn’s disease; FC: Fecal calprotectin; FIT: Fecal immunoassay test; MES: Mayo endoscopic subscore; UCEIS: Ulcerative colitis endoscopy index of severity; REI: Rachmilewitz endoscopic index; M2-PK: M2 pyruvate kinase, iFOBT: Immune fecal occult blood test; NA: Not available; QPOCT: Quantitative point-of-care test; AUC: Area under the curve; CI: Confidence interval; Sn: Sensitivity; Sp: Specificity.