Clinical impact of immunomonitoring in the treatment of inflammatory bowel disease

Table 1 Detecting anti-tumor necrosis factor-α trough levels

Study	Technique	Key Points
Ternant et al[21]	ELISA
Vande Casteele et al[24]	ELISA
Lu et al[26]	FO-SPR based sandwich bioassay	Faster than ELISA, correlates well
Malíčková et al[27]	ELISA (for CT-P13 biosimiliar to infliximab)
Corstjens et al[28]	Rapid lateral flow (LF)-based assay
Wang et al[29]	Non-radiolabeled homogeneous mobility shift assay (HMSA)

ELISA: Enzyme-linked immunosorbent assay; FO-SPR: Fiber-optic surface plasmon resonance.

Table 2 Detecting anti-tumor necrosis factor-α antibody levels

Ref.	Technique	Key points
Van Stappen et al[30]	Solid-phase ELISA	Lacks the ability to detect ADA in the presence of drug
Gils et al[25]	Solid-phase ELISA
Bloem et al[31]	Drug tolerant ELISA
Imaeda et al[23]	ELISA	Measures AAAs in the presence of free ADA
Van Stappen et al[32]	ELISA	Converts drug-sensitive bridging ELISA into a drug-tolerant bridging ELISA

ELISA: Enzyme-linked immunosorbent assay; ADA: Anti-tumor necrosis factor-α; AAA: Antibodies against adalimumab.

Table 3 Relationship between infliximab trough levels and response rates

Ref.	n	Mean IFX trough levels ug/mL	Mean IFX trough levels ug/mL	P value
		Lost response	Maintained response
Ainsworth et al[34]	27	0 (0-0.1)	2.9 (0.9-4.3)	0.002
Yamada et al[35]	31 (CD)	6.3	4.7	NS
Steenholdt et al[33]	69 (CD)	N/A	2.8 (0.8-5.3)	< 0.0001
Pariente et al[36]	76 (CD)	3.3 ± 4.1	2.3 ± 2.2	NS
Steenholdt et al[33]	13 (UC)	N/A	3.8 (1.1-8.5)	< 0.0001
Karmiris et al[37]	136 (CD)	0.3 (0.3-3.6)	4.9 (1.7-8.2)	0.01
Marits et al[38]	79 (CD)	1.8	4.1	< 0.001
Bortlik et al[39]	84 (CD)	N/A	> 3	N/A
Adedokun et al[40]	728 (UC)	N/A	3.7	N/A
Cornillie et al[41]	147 (CD)	1.9	4.0	0.0331
Reinisch et al[42]	203 (CD)	0.8	2.14	0.006

IFX: Infliximab; UC: Ulcerative colitis; CD: Crohn’s disease.

Table 4 Relationship between adalimumab trough levels and response rates

Study	n	Mean Adalimumab trough levels μg/mL	Mean Adalimumab trough levels μg/mL	P value
		Lost response	Maintained response
Imaeda et al[43]	40 (CD)	N/A	5.9	N/A
Roblin et al[44]	40 (UC/CD)	3.2	6.2	0.12

UC: Ulcerative colitis; CD: Crohn’s disease.

Table 5 Strategies to overcome loss of response

Dose escalate	Alternative cause for LOR?
Low trough	Adequate trough
No ADA	No ADA
Combination therapy	Alternative anti-TNFα/agent
Low trough	Low trough
ADA	ADA

ADA: Anti-TNFα; LOR: Loss of response.

Table 6 Trough levels associated with mucosal healing for infliximab

Study	n	Mean Infliximab Trough level μg/mL	Mean Infliximab Trough level μg/mL	P value	95%CI
		Mucosal Healing	No mucosal Healing
Paul et al[61]	52 (UC/CD)	Delta IFX > 0.5		0.0001
Ungar et al[63]	78 (UC/CD)	4.3	1.7	0.002
Imaeda et al[43]	45 (CD)	> 4.0			0.56-0.70
Reinisch et al[42]	123 (CD)	> 3.0			1.53-7.28
Colombel et al[64]	188 (CD)	3.51	1.72	0.0018
Papamichael et al[62]	101(UC)	> 15 (wk 6)		0.025
		> 2.1 (wk 14)		0.004

IFX: Infliximab; UC: Ulcerative colitis; CD: Crohn’s disease.

Table 7 Trough levels associated with mucosal healing for adalimumab

Study	n	Mean Adalimumab Trough level μg/mL	Mean Adalimumab Trough level μg/mL	P value
		Mucosal Healing	No mucosal Healing
Ungar et al[63]	67 (UC/CD)	6.7	3.1	0.01
Roblin et al[44]	40 (UC/CD)	6.5	4.2	< 0.05
Zittan et al[68]	60 (UC/CD)	14.7	3.4	< 0.0001

UC: Ulcerative colitis; CD: Crohn’s disease.