How to predict clinical relapse in inflammatory bowel disease patients

Table 1 Clinical and environmental predictors of relapse in inflammatory bowel diseases patients

	CD	UC
Clinical factors
Age	Young age at diagnosis[6-8,10]	Young age at diagnosis[11,14,15]
	→Disabling chronic disease
		→Rate of relapse
Sex		Female[11,14]
		→Rate of relapse
Disease location	Perianal disease[7,9]	Extensive colitis[8,14,16]
	→Poor outcome	→risk of colectomy, CRC, mortality
	Terminal ileal location[8,9]
	→Predictor of stricturing/penetrating disease; risk of surgical resection
	Proximal small bowel/upper gastro-intestinal tract[10,11]
	→risk of relapse; risk of surgical resection
	Colonic disease[6]
	→risk of develop perianal disease
No. prior relapses	Short period of remission before relapse[5,6]	Greater number of prior relapse
	→poor prognosis	→shorter time to relapse
EIM	NS[12]	NS[12]
Environmental factors
Smoke	Disease severity[19,20]	↓ disease severity[21]
Appendectomy	Risk of surgical resection[24]	↓ risk of colectomy[22,26]
Drugs
NSAIDs/ COX-2 selective	Contrasting evidences[28]	Contrasting evidences[28]
OCPs	Risk of relapse[20]	NS[15]
HRT	↓ disease severity[29]	↓ disease severity[29]
Antibiotics	↓ risk of relapse[30]	NS[30]
Stress	Risk of relapse[32]	Risk of relapse[31]

CD: Crohn’s disease; UC: Ulcerative colitis; CRC: Colon-rectal cancer; EIM: Extraintestinal manifestation; NS: No significant; NSAIDs: Non-steroidal anti inflammatory drugs; COX-2: Cyclooxygenase-2; OPCs: Oral contraceptive pills; HRT: Hormone replacement therapy.

Table 2 C-reactive protein as predictor of relapse in inflammatory bowel diseases patients

	No. Pt	No. R	Relapse rate	Mean CRP values R	Mean CRP values NR	P value
Brignola et al[5], 1986
CD	41	17	41%	2.2 mg/dL	0.7 mg/dL	0.010
Tibble et al[66], 2000
CD	43	25	58%	13.1 mg/L	9.1 mg/L	0.100
UC	37	19	51%	3 mg/L	9.7 mg/L	0.400
Bitton et al[15], 2001
UC	74	27	36.5%	0.08 mg/dL	0.25 mg/dL	NS
Costa et al[67], 2005
CD	38	15	39%	8 mg/L	6 mg/L	0.373
UC	41	19	46%	5 mg/L	4.5 mg/L	0.450
D'Incà et al[65], 2008
CD	65	20	31%	5.49 mg/L	3.13 mg/L	0.050
UC	97	37	38%	3.15 mg/L	3.08 mg/L	0.690
García-Sánchez et al[69], 2010
CD	66	18	27%	4.6 mg/L	5.6 mg/L	0.790
UC	69	21	31%	3.8 mg/L	1.7 mg/L	0.060
Kallel et al[62], 2010
CD1	53	10	18.9%	34 mg/L	4 mg/L	< 0.001
Naismith et al[70], 2014
CD	45	5	11%	2	2.1	0.539

¹Small bowel CD patients excluded. R: Relapsers; NR: Non relapsers; CRP: C reactive protein; CD: Crohn’s disease; UC: Ulcerative Colitis; IBD: Inflammatory bowel diseases.

Table 3 Erythrocyte sedimentation rate as predictors of relapse in inflammatory bowel diseases patients

	No. Pt	No. R	Relapse rate	Mean ESR values R (mm/h)	Mean ESR values NR (mm/h)	P value
Brignola et al[5], 1986
CD	41	17	41%	24	9	0.0006
Tibble et al[66], 2000
CD	43	25	58%	21	13	0.200
UC	37	19	51%	13	20	0.200
Bitton et al[15], 2001
UC	74	27	36.5%	13.8	11	NS
Costa et al[67], 2005
CD	38	15	39%	20	15	0.077
UC	41	19	46%	15	11	0.056
D'Incà et al[65], 2008
CD	65	20	31%	25	15	0.005
UC	97	37	38%	14	11	0.690
García-Sánchez et al[69], 2010
CD	66	18	27%	17.5	16.2	0.230
UC	69	21	31%	14.1	7.6	0.180

R: Relapsers; NR: Non relapsers; ESR: Erythrocyte sedimentation rate; CD: Crohn’s disease; UC: Ulcerative Colitis; IBD: Inflammatory bowel diseases.

Table 4 Fecal calprotectin as a predictor of relapse in inflammatory bowel disease patients

IBD type	Criteria for defining relapse	No. Pt	No. R	Relapse rate	Mean FC values R	Mean FC values NR	P value	FC cut off	Se	Spe	PPV	NPV	HR7
Tibble et al[66], 2000
CD	CDAI > 150 ΔCDAI > 100	43	25	58%	122 mg/L (610 μg/g)	41.5 mg/L (220 μg/g)	< 0.0001
UC	HBI > 4 ΔHBI > 2	37	19	51%	123 mg/L	29 mg/L	< 0.0001
IBD		80	44	55%	123 mg/L	32 mg/L	< 0.0001	50 mg/L (250 μg/g)	90	83
Costa et al[67], 2005
CD	CDAI > 150	38	15	39.5%	220.1 μg/g	220.5 μg/g	0.395	150 μg/g	87	43	50	83	2.20
UC	UCAI > 4	41	19	46.3%	220.6 μg/g	67 μg/g	< 0.0001	150 μg/g	89	82	81	90	14.40
IBD		79	34	43%
D'Incà et al[65], 2008
CD	CDA ≥ 150 ΔCDAI > 50	65	20	31%	207 mg/kg	88 mg/kg	0.055	130 mg/kg	65	62	44	80	1.70
Colonic CD					176.7 mg/kg	75.1 mg/kg	0.041
UC	ET > 4	97	37	38%	190 mg/kg	49 mg/kg	0.001	130 mg/kg	70	70	60	79	2.40
IBD		162	57	35.2%				130 mg/kg	68	67	52	79
Gisbert et al[68], 2009
CD	CDAI > 150	89	13	14.6%	266 μg/g	145 μg/g	0.002	169 μg/g	69	76
UC	TW > 11	74	13		213 μg/g	126 μg/g	0.030	164 μg/g	69	74
IBD		163	26	16%	239 μg/g	136 μg/g	< 0.001	167 μg/g	69	75	35	93	2.80
García-Sánchez et al[69], 2010
CD	CDAI ≥ 150	66	18	27%	524 μg/g	123 μg/g	< 0.010	200 μg/g	80	65	46	88	4.35
UC	TW ≥ 11	69	21	31%	298 μg/g	105 μg/g	< 0.010	120 μg/g	81	63	49	88	6.48
IBD		135	39	30%	444 μg/g	112 μg/g	< 0.010	150 μg/g	75	68	49	68
Kallel et al[62], 2010
CD1	CDAI > 150 ΔCDAI > 100	53	10	18.9%	380.5 μg/g	155 μg/g	< 0.001	340 μg/g	80	90.7			18.80
Naismith et al[70], 2014
CD	Treatment modification, progression disease phenotype, hospitalization, surgery	92	10	11%	414 μg/g	96 μg/g	0.005	240 μg/g	80	74.4	27.6	96.8	12.18
Colonic CD		35	4		424 μg/g	187	0.160
Ileal CD		16	3		371 μg/g	57	0.057
Yamamoto et al[74], 2014
UC		80	21	26%	173.7 μg/g	135.5 μg/g	0.020	170 μg/g	76	76			7.23
Scaioli et al[111]
UC	SCCAI > 3	74	20	27%	218 μg/g	48 μg/g	< 0.010	193 μg/g	65	98	92	88
	Mayo > 1

¹Small bowel CD patients excluded. 12-mo follow-up period in all the studies cited; FC assay was Calprest for all the studies cited, except in the study by Tibble et al[66] (Roseth). R: Relapsers; NR: Non relapsers; FC: Fecal calprotectin; Se: Sensibility; Spe: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; HR: Hazard ratio; CD: Crohn’s disease; UC: Ulcerative Colitis; IBD: Inflammatory bowel diseases; HBI: Harvey Bradshaw Index; CDAI: Crohn’s disease activity index; CAI: Colitis activity index; TW: Modified Truelove-Witt; SCCAI: Simple Clinical Colitis Activity.