Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn’s disease under infliximab therapy

Table 4 Previous research of infliximab trough level on deep remission in inflammatory bowel disease

Study design	Optimal cut-off value	Predictive content	Yes/No, n	SE	SP	PPV	NPV	AUC
A retrospective observational single-center study in China	4.85 μg/mL at week 14	Mucosal healing (complete absence of any sign of ulceration)	82/59	67%	80%			0.80
	4.85 μg/mL at week 14	Mucosal healing (CDEIS of < 3)	84/57	68%	83%			0.79
	2.85 μg/mL at week 30	Mucosal healing (complete absence of any sign of ulceration)	59/50	73%	84%			0.78
	2.85 μg/mL at week 30	Mucosal healing (CDEIS of < 3)	62/47	68%	81%			0.73
A retrospective observational single-center study in China	2.50 μg/mL at week 14	Mucosal healing (SES-CD/Rutgeerts of 0 or 1) at week 52	31/42	87%	60%			0.70
	2.50 μg/mL at week 14	Sustained remission (no treatment failure, no need for surgery or intensification of IFX nor new introduction during IFX therapy) at week 52	70/38	64%	63%			0.70
A prospective multicenter study in Spanish	3.40 μg/mL	(1) SES-CD<3 for CD patients; (2) Rutgeerts score < i2 for CD patients in the postoperative setting; and (3) Mayo endoscopic score < 2 for UC patients	58/30	60%	60%	73%	42%	0.63
A multicenter, randomized, double-blind, controlled trial in Europe	23.10 mg/L at week 2	Endoscopic remission (CDEIS < 3) at week 12	54/52	56%	80%	72%	65%	0.67
	10.00 mg/L at week 6	Endoscopic remission (CDEIS < 3) at week 12	54/52	37%	89%	76%	59%	0.64
	10.60 mg/L (dose escalation to 10 mg/kg)	The absence of ulcers at week 54	85/51	94%	42%	49%	92%	0.71
A retrospective multicenter study in United States	9.70 μg/mL	Endoscopic remission (absence of any mucosal break (ulceration or erosion)/Rutgeerts score of ≤ i1)	62/34	57%	73%	80%	48%	0.65
	9.80 μg/mL	Histologic remissions (absence of active inflammation)	43/44	63%	66%	64%	64%	0.62
	2.20 μg/mL	Biochemical remission (CRP ≤ 5 mg/dL)	48/23	92%	35%	75%	67%	0.64
A retrospective observational single-center study in Japan	4.00 μg/mL	Mucosal healing (modified Rutgeerts scoring system: 0 or 1) after 30 days	20/58	71%	70%			0.63
	0.60 μg/mL	CRP normalization (≤ 0.3 mg/dL)	28/22	73%	62%			0.67
	1.00 μg/mL	Serum albumin normalization (≥ 4.0 mg/dL)	17/33	67%	71%			0.72
	1.10 μg/mL	Fecal calprotectin (≥ 300 μg/g)	13/25	72%	56%			0.63
A retrospective cross-sectional multicenter study in South Korea	4.20 μg/mL	Mucosal healing (SES-CD = 0)	51/54	65%	70%	67%	68%	0.68
	3.71 μg/mL	Partial mucosal healing (SES-CD < 3)	63/42	70%	71%	79%	61%	0.73
	3.26 μg/mL	Clinical remission (PCDAI < 10)	95/10	71%	100%	100%	73%	0.90
	2.52 μg/mL	Biochemical remission (CRP < 0.3 mg/dL)	87/18	86%	56%	90%	46%	0.71
A prospective cohort multicenter study in Canada	8.02 μg/mL	Histologic remission (an absence of active chronic inflammation)	56/48	79%	68%			0.72
	8.27 μg/mL	Sustained histologic remission (histologic remission documented at both the baseline and follow-up colonoscopies)	36/16	88%	72%			0.77
A retrospective cross-sectional study in United Kingdom	7.10 μg/mL	Fistula healing (no spontaneous discharge or no discharge on palpation in the absence of seton drainage)	18/11	78%	100%			0.93
	7.10 μg/mL	Fistula closure (the absence of an external skin opening)	13/16	64%	100%			0.97

SE: Sensitivity; SP: Specificity; PPV: Positive predictive value; NPV:Negative predictive value; AUC: Areas under the curve; CDEIS: Crohn’s disease endoscopic index of severity; SES-CD: Simplified endoscopic score for Crohn’s disease; CD: Crohn’s disease; UC: Ulcerative colitis; CRP: C-reactive protein; PCDAI: Pediatric Crohn’s disease activity index.