Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy

Table 1 Inflammatory bowel disease patient demographics and characteristic

Characteristics	n or mean ± SD (range)
Male:female	7:11
Age at diagnosis(yr)	26.6 ± 11.3 (12-56)
Disease duration	8.4 ± 7.9 (0-30)
Montreal classification
CD	13
UC	5
Age at diagnosis (yr)
A1 ( ≤ 16)	1
A2 (17-40)	14
A3 (> 40)	3
Smoking status
Never smoked	7
Ex-smoker	5
Current smoker	6
Anti-TNF response
Responder	13
Non-responder	5

CD: Crohn’s disease; UC: Ulcerative colitis; TNF: Tumor necrosis factor.

Table 2 Clinical data of responders and non-responders

	Responders (n = 13) (n or mean ± SEM)	Non-responders (n = 5) (n or mean ± SEM)	P value
Immuno-suppressants
Thiopurine	10	4	NS
Tacrolimus	0	0
Prednisone	6	4	NS
Prednisone/thiopurine	5	2	NS
Methotrexate	0	0
5-ASA	1	2
Corticosteroids	9	2	NS
ESR	23.9 ± 4.8 (n = 11)	9.6 ± 2.2 (n = 4)	NS
CRP	25.8 ± 6.8 (n = 13)	9.2 ± 3.7 (n = 4)	NS
Partial Mayo1 (out of 9 - UC patients only)	8 ± 1.3 (n = 3)	8 (n = 3)	NS
CDAI (CD patients only)	321.9 ± 35.4 (n = 9)	385 ± 55 (n = 3)	NS

¹Partial Mayo scores presented, as not all patients had endoscopic examination at time of blood draw. CDAI: Crohn’s disease activity index; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; UC: Ulcerative colitis.

Table 3 Crohn’s disease vs ulcerative colitis pre-anti-tumour necrosis factor therapy

	CD (n = 13) (n or mean ± SEM)	UC (n = 5) (n or mean ± SEM)	P value
Immunosuppressant
Thiopurine	10	4	NS
Tacrolimus	0	0
Prednisone	6	4	NS
Prednisone/thiopurine	3	3
Methotrexate	0	0
5-ASA	2	3	NS
ESR	17.4 ± 3.3 (n = 11)	27.6 ± 11.8 (n = 4)	NS
CRP	19.5 ± 6.3 (n = 13)	29.8 ± 12 (n = 4)	NS
Partial Mayo1 (out of 9 - UC patients only)	-	8.5 ± 0.9 (n = 4)
CDAI (CD patients only)	337 ± 29.8 (n = 12)	-

¹Partial Mayo scores were presented, as not all patients had undergone endoscopic examination at time of blood draw. CD: Crohn’s disease; CDAI: Crohn’s disease activity index; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; UC: Ulcerative colitis.

Table 4 Ulcerative colitis cohort demographics and characteristics

	UC non-responders (NR) (n = 12)	UC responders (R) (n = 12)	P value	Controls
			NR vs R	(n = 12)
Male:female	6:6	4:8	NS	4:8
Mean age at diagnosis (yr) (SD/range)	27.5 (12.2/15-59)	24.5 (8.8/10-36)	NS	N/A
Mean age at assessment (yr) (SD/range)	33.6 (14/20-67)	38.6 (14.2/21-64)	NS	33.4 (13/18-52)
Mean Disease duration (yr) (SD/range)	6.9 (2.7/13.1/20-67)	17.5 (10.6/4-37)	0.01	N/A
Median time of blood draw post-therapy (wk) (range)	156 (12-364)	208 (12-468)	NS	N/A
Montreal classification, n				N/A
Age at diagnosis (yr)
A1 - ≤ 16	1	1	NS
A2 - 17-40	9	10	NS
A3 - > 40	2	1	NS
Disease location
E1 - Proctitis	2	0	NS
E2 - Left sided	1	4	NS
E3 - Extensive	9	8	NS
Smoking status (n)
Never smoked	8	8	NS	8
Ex-smoker	3	4	NS	2
Current smoker	1	0	NS	2

UC: Ulcerative colitis.

Table 5 Clinical data pre- and post-anti-tumour necrosis factor therapy

	Non-responder (n = 12)	Responder (n = 12)	P value
	(n or mean ± SEM)	(n or mean ± SEM)
Pre-anti-TNF therapy
Immunosuppressant
Thiopurine	7	6	NS
Tacrolimus	2	0	NS
Prednisone	9	7	NS
Prednisone/thiopurine	6	2	NS
Methotrexate	1	0
5-ASA	6	5	NS
ESR	42.5 ± 12.9 (n = 7)	33.1 ± 10.4 (n = 7)	NS
CRP	36.3 ± 10.1 (n = 11)	27.4 ± 7.4 (n = 12)	NS
Partial Mayo1	7.3 ± 0.5 (n = 7)	7.5 ± 0.2 (n = 11)	NS
Post-anti-TNF therapy
Immunosuppressant
Thiopurine	12	8	NS
Tacrolimus	4	0	0.045
Prednisone	6	0	0.007
Prednisone/thiopurine	0	0
Methotrexate	0	0
5-ASA	6	4	NS
ESR	22.9 ± 7.9 (n = 4)	13.5 ± 4.7 (n = 9)	NS
CRP	51.2 ± 14.6 (n = 12)	4.6 ± 1.2 (n = 12)	0.0043
Partial Mayo1	7.6 ± 0.4 (n = 12)	0.3 ± 0.2 (n = 12)	< 0.0001

¹Partial Mayo scores presented as not all patients had endoscopic examination at time of blood draw. CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.