Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease: Case series and review of literature

Table 1 Management of secondary loss of response

	No/low antibody level	High antibody level
Low drug level	Increase drug dose	Change therapy (within class or alternate class)
Normal/high drug level	Change therapy (alternate class)	(Not clinically relevant scenario)

Table 2 A total of twelve patients on either infliximab or adalimumab were included in the case serie

Patient	Age (yr)	Sex	Diagnosis	Montreal classification	Duration of disease (yr)	Previous anti-TNF therapy?	Immunomodulator therapy?
1	24	M	CD	A2L3B1	5	Y	Previous - MTX
2	46	M	UC	E3	10	N	Previous - 6MP
3	71	M	CD	A3L1B2	4	N	Previous - 6MP
4	31	F	CD	A2L1B2	9	Y	Current - 6MP
5	46	F	CD	A2L3B2p	5	N	None
6	41	M	UC	E2	18	N	Current - AZA
7	53	F	UC	E2	24	Y	Previous - MTX
8	21	M	UC	E3	1	N	Current - MTX
9	67	M	CD	A3L2B1	3	N	None
10	26	M	CD	A1L2B1	11	N	None
11	49	F	CD	A2L3B2	30	N	None
12	25	M	CD	A2L1B2	7	Y	Current - MTX

Montreal classification CD: Age at Diagnosis (A1: Less than 16 years; A2: Between 17 and 40 years; A3: Over 40 years). Location (L1: Ileal; L2: Colonic; L3: Ileocolonic; L4: Isolated upper digestive tract). Behavior (B1: Non-stricturing, non-penetrating; B2: Structuring; B3: Penetrating; p: Perianal). Montreal classification UC: Location (E1: Proctitis; E2: Left-sided; E3: Extensive or pancolitis). M: Male; F: Female; CD: Crohn’s disease; UC: Ulcerative colitis; MTX: Methotrexate; 6-MP: 6-mercaptopurine; AZA: Azathioprine; TNF: Tumor necrosis factor.

Table 3 Adjustment therapy at the time of the study

Pt	Dx	Anti-TNF drug	On immuno-modulator?1	Reason for TDM	Predrug level	Pre-Ab level	Adjustment in therapy	Post-drug level	Post-Ab level	Resolved ADAs?	Did patient have improvement?
1	CD	ADA	N	Endoscopic disease	3.0 μg/mL	38 ng/mL	Frequency	10 μg/mL	< 25 ng/mL	Y	Symptom improvement; fecal calprotectin
2	UC	ADA	N	Flare symptoms	< 1.6 μg/mL	4.6 U/mL	Dose/ frequency	13.7 μg/mL	< 1.7 U/mL	Y	Symptom
											improvement; decreased CRP
3	CD	ADA	N	Flare symptoms	3.3 μg/mL	2.6 U/mL	Frequency	5.8 μg/mL	0	Y	Symptom
											improvement
4	CD	ADA	Y - 6MP	Flare symptoms, Endoscopic disease	2.6 μg/mL	66 ng/mL	Frequency	4.8 μg/mL	< 25 ng/mL	Y	Symptom
											improvement
5	CD	IFX	N	Flare symptoms	4.1 μg/mL	4.5 U/mL	Dose/ frequency	23.4 μg/mL	< 3.1 U/mL	Y	Symptom improvement; CRP
6	UC	IFX	Y - AZA	Flare symptoms	1.1 μg/mL	8.2 U/mL	Dose	16.9 μg/mL	< 3.1 U/mL	Y	Symptom improvement
7	UC	IFX	N	Flare symptoms; Endoscopic disease	10.4 μg/mL	5.0 U/mL	Added immuno-modulator (MTX)	11.3 μg/mL	0	Y	Symptom improvement; ESR
8	UC	IFX	Y - MTX	Flare symptoms	0	5.5 U/mL	Dose	26.8 μg/mL	0	Y	ESR/CRP
9	CD	IFX	N	Flare symptoms	23.1 μg/mL	8.6 U/mL	Dose	< 1 μg/mL	88.6 U/mL	N	-
10	CD	IFX	N	Endoscopic disease	< 1.0 μg/mL	3.7 U/mL	Frequency	< 0.4 μg/mL	34 ng/mL	N	-
11	CD	ADA	N	Flare symptoms	5.6 μg/mL	3.1 U/mL	Frequency	4.6 μg/mL	113 ng/mL	N	-
12	CD	IFX	Y - MTX	Flare symptoms	< 1 μg/mL	8.2 U/mL	Frequency	8.2 μg/mL	9.0 U/mL	N	-

¹Refers to concurrent immunomodulator therapy. Pt: Patient; Dx: Diagnosis; TDM: Therapeutic drug monitoring; Ab: Antibody; ADA: Antidrug antibody; CD: Crohn’s disease; UC: Ulcerative colitis; ADA: Adalimumab; IFX: Infliximab; AZA: Azathioprine; 6MP: 6-mercaptopurine; MTX: Methotrexate; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein.