Table 4

Anti-TNF therapy immunogenicity–therapeutic outcomes relationship in IBD

Drug	IBD type	Study type	No	Time point	ADA	Therapeutic outcome	Method	Ref.
Clinical efficacy
IFX	CD/UC	Retrospective	90 (CD: 64)	Induction and maintenance*	Detectable	Treatment failure and discontinuation	HMSA	11
IFX	CD/UC	Retrospective	90 (CD: 64)	Induction and maintenance*	>9.1 U/mL	Failure of dose intensification after SLR	HMSA	11
IFX	CD/UC	Retrospective	128 (CD: 105)	Induction after drug holiday	Undetectable	Short-term clinical response	HMSA	63
IFX	CD	Prospective	125	Maintenance	>8 μg/mL-eq	Shorter clinical response	ELISA	23
IFX	CD/UC	Cross-sectional (paediatric)	134 (CD: 114)	Maintenance	>12 U/mL	Surgery	HMSA	56
ADM	CD	Retrospective	130	Maintenance	Detectable	Treatment discontinuation	ELISA	26
ADM	CD	Retrospective	30	Maintenance	Detectable†	No clinical response	RIA	57
ADM	CD	Cross-sectional	118	Maintenance	Detectable‡	Active disease	ELISA	29
Endoscopic and biomarker outcomes
IFX	UC	Prospective	19	Induction	Detectable	No endoscopic response	HMSA	32
IFX	UC	Retrospective	101	Induction (w6)	Detectable	No mucosal healing	ELISA§	31
IFX	CD	Retrospective	45	Maintenance	Detectable	No mucosal healing	ELISA	18
IFX	CD/UC	Cross-sectional	78 (CD: 53)	Maintenance	Undetectable	Mucosal healing	ELISA	15
IFX	CD	Prospective	327	Maintenance	Detectable	CRP >5 mg/L	HMSA	22
IFX	CD	Observational¶	483	Maintenance	Detectable	CRP >5 mg/L	HMSA	35
ADM	CD	Prospective	40	Maintenance	Detectable	Higher CRP and ESR	ELISA	36
Loss of response
IFX	CD/UC	Prospective	125 (CD: 98)	Induction and maintenance	Detectable	SLR	ELISA	52
IFX	CD/UC	Case–control	62 (CD: 51)	Maintenance	Detectable	SLR	ELISA	58
IFX	CD	Prospective	53	Maintenance	Detectable**	SLR	ELISA	53
IFX	CD/UC	Prospective	93 (CD: 59)	Maintenance (w22)	Detectable stable ATI††	SLR	ELISA	12
IFX	CD	Retrospective	33	Maintenance	Detectable	SLR	RIA	59
IFX	CD	Retrospective (paediatric)	28	Maintenance	Detectable	SLR	ELISA	60
IFX	CD	Retrospective	106	Maintenance	Detectable‡‡	SLR	RIA	14
ADM	CD	Retrospective	148	Maintenance	Detectable	SLR§§	HMSA	25
ADM	CD/UC	Retrospective	72 (CD: 53)	Maintenance	Detectable	SLR§§	RIA	61
ADM	CD/UC	Retrospective	57 (CD: 42)	Maintenance	Detectable	SLR	RIA	28

*Ever had a positive ATI.
†>12 U⁄mL.
‡≥3 μg/mL-eq.
§Recently developed drug-tolerant assay.
¶Four clinical studies.11 ,22 ,37 ,38
**IFX level ≤1.4.
††Two consecutive ATI >20 ng/mL.
‡‡>10 U/mL.
§§Drug discontinuation.
ADA, antidrug antibody; ADM, adalimumab; ATI, antibodies to infliximab; CD, Crohn's disease; CRP, C reactive protein; eq, equivalent; ESR, erythrocyte sedimentation rate; HMSA, homogeneous mobility shift assay; IBD, inflammatory bowel disease; IFX, infliximab; No, number of patients; RIA, Radio-immunoassay; SLR, secondary loss of response; U, units; UC, ulcerative colitis.