Are faecal markers good indicators of mucosal healing in inflammatory bowel disease?

Table 1 Studies investigating the correlation between faecal calprotectin concentrations and endoscopic activity in subjects with inflammatory bowel diseases

Ref.	Number of participants		Population	Endoscopic index used	Endoscopic indexcut off	Faecal calprotectincut off (μg/g)	Outcome measures				Correlation
	CD	UC					Sensitivity	Specificity	PPV	NPV	r value	P value
Crohn’s disease studies
Falvey et al[46]	59		Adults	SES-CD	≤ 3	125	71%	71%	85%	50%	0.55%	< 0.0001
						200	60%	79%	88%	45%
Lobatón et al[51]	85		Adults	CDEIS	< 3	274 ELISA	77%	97%	75%	98%	0.784%	< 0.001
					< 3	272 QPOC	79%	97%	76%	98%	0.722%	< 0.001
					0	262 ELISA	75%	76%
					0	200 QPOC	75%	77%
Nancey et al[45]	78		Adults	SES-CD	≤ 2	250	71%	78%	79%	71%	0.53%	< 0.0001
						100	88%	38%	62%	73%
D’Haens et al[47]	87		Adults	CDEIS	≤ 3	< 250	94.1%	62.2%	48.5%	96.6%	0.419%	< 0.001
				SES-CD	0	< 250	51.6%	82.6%	89.2%	38%	0.49%	< 0.001
af Björkesten et al[15]	64		Adults	SES-CD	≤ 2	< 100	81%	74%	-	-	0.56%	< 0.001
						< 94	84%	74%	-	-
				SES-CD	0	< 94	82%	78%	-	-
Aomatsu et al[16]	18		Paediatrics	SES-CD	0	100	94.7%	50%	87.8%	71.4%	0.76%	< 0.01
						150	94.7%	50%	87.8%	71.4%
Sipponen et al[17]	19		Adults	SES-CD	≤ 2	< 100	-	80%	-	-	-	-
Schoepfer et al[21]	122		Adults	SES-CD	≤ 3	< 50	89%	58%	89%	61%	0.75%	< 0.01
						< 70	89%	72%	88%	76%
Langhorst et al[23]	43		Adults	SES-CD		> 6	100%	30%	82.5%	100%	0.35%	< 0.05
						> 48	81.8%	80%	93.1%	57.1%
Schoepfer et al[22]	36		Adults	SES-CD	≤ 19	50	-	-	-	-	-	< 0.0001
Sipponen et al[18]	61		Adults	SES-CD (total)	≤ 3	< 100	-	-	-	-	0.662%	< 0.001
				SES-CD (colon)	≤ 3	< 100	-	-	-	-	0.642%	< 0.001
				SES-CD (ileal)	≤ 3	< 100	-	-	-	-	0.317%	> 0.05
Sipponen et al[19]	15		Adults	CDEIS	≤ 2	< 200	87%	100%	100%	70%	0.831%	< 0.001
Sipponen et al[20]	77		Adults	CDEIS	≤ 2	< 50	91%	44%	76%	73%	0.729%	< 0.001
						< 100	81%	69%	84%	66%
						< 200	70%	92%	94%	61%
Jones et al[24]	164		Adults	SES-CD	≤ 6	≤ 50	-	-	-	-	0.45%	< 0.05
Denis et al[25]	28		Adults	CDEIS	≤ 5	< 50	-	-	-	-	-	0.57
Schoepfer et al[26]	24		Adults	SES-CD	≤ 19	< 50	-	-	-	-	-	0.0001
D'Incà et al[28]	31		Adults	SES-CD		> 80	-	-	-	-	0.48%	0.008
Mixed inflammatory bowel disease population studies
Molander et al[29]	183	69	Mixed	SES-CD; Mayo	≤ 2; ≤ 1	< 100	-	-	-	72%	-	< 0.0001
Vieira et al[30]	38	40	Adults	CDEIS; Mayo	≤ 2; ≤ 2	> 200.01	88.6%	97.1%	97.5%	86.8%	-	0
Schoepfer et al[22]	36	28	Adults	SES-CD; Rachmilewitz	≤ 19; ≤ 4	50	-	-	-	-	-	< 0.0001
Canani et al[50]	26	32	Paediatrics	Saverymuttu	≤ 1	143	-	-	-	-	0.46%	≤ 0.05
Fagerberg et al[31]	27	10	Paediatrics	Saverymuttu		< 85.7	-	-	-	-	0.65%	< 0.001
Silberer et al[32]	21	18	Adults	Stange		18.6	61.5%	95%	-	-	-	< 0.0001
Røseth et al[33]	17	28	Adults	Farup		< 50	0%	100%	-	97.8%	-	-
Bunn et al[34]	2	9	Paediatrics	Saverymuttu			-	-	-	-	0.65%	< 0.05
Ulcerative colitis studies
Falvey et al[46]		38	Adults	Baron	0	125	74%	80%	85%	67%	0.55%	< 0.0001
						200	58%	95%	95%	59%
Nancey et al[45]		55	Adults	Rachmilewitz	≤ 2	250	91%	87%	87%	91%	0.75%	< 0.0001
						100	100%	53%	85%	100%
Kristensen et al[48]		62	Adults	Mayo	0	61 Cal	84.1%	83.3%	92.5%	68.2%		< 0.001
					0	96 BM	90.9%	83.3%	93%	78.9%		< 0.001
					≤ 1	110 Cal	80%	66.6%	69.2%	78%
					≤ 1	259 BM	83.3%	71.9%	73.5%	82.1%
D’Haens et al[47]		39	Adults	Mayo	0	< 250	71%	100%	100%	47.1%	0.56%	< 0.001
Komraus et al[35]		16	Paediatrics	Rachmilewitz		< 50	-	-	-	-	0.52%	0.0391
Aomatsu et al[16]		17	Paediatrics	Matts	≤ 6	100	94.1%	50%	88.9%	66.7%	0.84%	< 0.01
						150	91.2%	87.5%	96.9%	70%
Schoepfer et al[27]		115	Adults	Rachmilewitz	< 4	< 50	93%	71%	91%	81%	0.83%	< 0.001
						< 100	86%	88%	96%	65%
Langhorst et al[23]		42	Adults	Mayo		> 6	100%	6.7%	6.6%	100%	0.49%	< 0.001
						> 48	81.5%	72.3%	84.6%	68.8%
Schoepfer et al[22]		28	Adults	Rachmilewitz	≤ 4	50	-	-	-	-	-	0.0025
Schoepfer et al[26]		12	Adults	Rachmilewitz	≤ 1	< 50	-	-	-	-	-	0.0335
D'Incà et al[28]		46	Adults	Mayo		> 80	-	-	-	-	0.511%	0.001
Hanai et al[36]		31	Adults	Matts	≤ 1		-	-	-	-	0.81%	< 0.001
Røseth et al[37]		62	Adults	Sandborn	≤ 1	< 10	-	34%	-	-	0.57%	< 0.0001
						< 20	-	62%	-	-

CD: Crohn’s disease; UC: Ulcerative colitis; PPV: Positive predictive value; NPV: Negative predictive value; SES-CD: Simple endoscopic score for Crohn’s disease[54]; CDEIS: Crohn’s disease endoscopic index of severity[55]; ELISA: Enzyme linked immunosorbant assay; QPOC: Quantitative point of care test; Mayo: Mayo endoscopic sub-scoring of ulcerative colitis[56]; Rachmilewitz: Rachmilewitz endoscopic score[57]; Saverymuttu: Non-standard endoscopic scoring system[58]; Stange: Non-standard endoscopic scoring system[59,60]; Farup: Non-standard endoscopic scoring system[61]; Baron: Baron score; Matts: Matts score[62]; Sandborn: Non-standard endoscopic scoring system[63]; Cal: Calpro ELISA: Calpro Calprotectin ELISA, Calpro AS, Norway; BM: BM ELISA, EK-CAL, Buhlmann Laboratories AG, Switzerland; Farmer: Non-standard endoscopic scoring system[64]; Faecal Hb: Faecal haemoglobin; PMN-e: Polymorhonuclear elastase; Hb-Hp: Haemoglobin; Haptoglobin complex; D’Haens: Non-standard histologic scoring system[65]; Fazio: Non-standard histologic scoring system[66]; Floren: Non-standard histologic scoring system[67].