Significant risk and associated factors of active tuberculosis infection in Korean patients with inflammatory bowel disease using anti-TNF agents

Table 1 Baseline characteristics of patients treated with anti-TNF agent

	n = 376
Sex (male:female)	255:121
Age of diagnosis (yr)	27.9 ± 12.6
Age at the start of anti-TNFs (yr)	32.5 ± 13.0
Follow-up (mo)	81.6 ± 58.9
Diseases
Crohn’s disease	277 (73.7)
L1/L2/L3/L1+L4/L3+L4	48/60/157/4/8
B1/B2/B3	102/87/88
Perianal disease	160 (42.5)
Ulcerative colitis	99 (26.3)
E1/E2/E3	8/45/46
Previous anti-TB treatment	8 (2.1)
Diabetes Mellitus	12 (3.2)
Anti-TNF agents
Infliximab	294 (78.2)
Adalimumab	82 (21.8)

Data are espressed as n (%) or mean ± SD. TB: Tuberculosis; UC: Ulcerative colitis.

Table 2 Screening outcomes for latent tuberculosis infection before anti-TNF agent

	n = 376, n (%)
Chest X-ray
Done	356 (94.7)
Old tuberculosis	8/356 (2.2)
Negative	348/356 (97.8)
IGRA
Unknown	9 (2.4)
Done	276 (73.4)
Positive	16/276 (5.8)
Negative	241/276 (87.3)
Indeterminate	19/276 (6.9)
Steroid or thiopurine at IGRA	214/276 (77.5)
QuantiFERON	247 (62.9)
Positive	14/247 (5.7)
Negative	218/247 (88.3)
Indeterminate	15/247 (6)
T-SPOT	29 (12.6)
Positive	2/29 (6.9)
Negative	23/29 (79.3)
Indeterminate	4/29 (13.8)
TST
Unknown	10 (2.7)
Done	131 (34.8)
Positive	12/131 (9.2)
Negative	117/131 (89.3)
Steroid or thiopurine at TST	104/131 (79.4)
Screening tests for LTBI
1 test (IGRA or TST)	211 (56.1)
2 tests (IGRA and TST)	98 (26.1)
Neither IGRA or TST	59 (15.7)
Latent tuberculosis infection	30 (8.0)

IGRA: Interferon gamma release assay; TST: Tuberculin skin test; LTBI: Latent tuberculosis infection.

Table 3 Clinical characteristics of patients developing active tuberculosis infection after anti-TNF agent

No.	IBD	Sex	Age of anti-TNFs (yr)	Anti-TNFs	Previous TB treatment	Screening IGRA	Screening TST	IS at screening	Prophylaxis	Interval to TB infection (wk)	IS at TB diagnosis	Extra-pulmonary TB	No. of involvement organ
1	CD	F	21	IFX	No	ND	ND	None	ND	83	CS + AZA	No	1
2	CD	M	24	ADA	No	+	ND	CS	INH	22	None	Yes	1
3	CD	M	24	IFX	No	-	ND	CS +AZA	ND	35	AZA	Yes	3
4	CD	M	42	IFX	Yes	-	ND	CS	ND	46	CS + AZA	Yes	6
5	CD	F	34	IFX	Yes	-	ND	AZA	ND	23	AZA	Yes	1
6	CD	M	29	IFX	No	-	ND	AZA	ND	10	AZA	Yes	5
7	CD	M	41	IFX	No	ND	-	AZA	ND	12	AZA	Yes	1
81	CD	M	24	IFX	No	ND	-	CS	ND	8	CS	Yes	4
9	CD	M	27	IFX	No	ND	-	AZA	ND	22	AZA	No	1
10	CD	M	23	IFX	Yes	+	-	AZA	ND	8	CS + AZA	Yes	1
11	CD	M	21	IFX	No	-	Unknown	CS +AZA	ND	129	CS + AZA	Yes	3
12	UC	M	32	IFX	No	+	ND	AZA	INH + RFP	40	AZA	Yes	4
13	UC	M	70	IFX	No	-	ND	AZA	ND	142	AZA	No	1
14	UC	M	21	IFX	No	-	ND	CS +AZA	ND	52	AZA	Yes	3
15	UC	M	56	IFX	No	-	ND	AZA	ND	47	AZA	Yes	2
16	UC	F	25	IFX	No	+	-	AZA	ND	12	AZA	Yes	2

¹This patient died 55 d after miliary tuberculosis diagnosis due to devastating acute renal failure. IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis; IFX: Infliximab; ADA: Adalimumab; ND: Not done; TB: Tuberculosis; IGRA: Interferon gamma release assay; TST: Tuberculin skin test; IS: Immunosuppressant; CS: Corticosteroid; AZA: Azathioprine; INH: Isoniazid; RFP: Rifampin.

Table 4 Univariate analysis of risk factors for active tuberculosis infection after anti-TNF therapy n (%)

	TB infection + (n = 16)	TB infection - (n = 360)	P value
Age at anti-TNF (yr)	26 (21-70)	30 (11-76)	0.808
Female	3 (18.8)	118 (32.8)	0.287
Diseases			0.772
Crohn’s disease	11 (68.8)	266 (73.9)
Ulcerative colitis	5 (31.3)	94 (26.1)
Diabetes mellitus	1 (6.3)	11 (3.1)	0.411
Anti-TNF agent			0.212
Infliximab	15 (93.8)	279 (77.5)
Adalimumab	1 (6.3)	81 (22.5)
LTBI	4 (25)	26 (7.2)	0.031
IM at anti-TNF agent	13 (81.3)	228 (63.3)	0.187
WBC count < 5000 mm3	10 (62.5)	115 (31.9)	0.015

LTBI: Latent tuberculosis infection; IM: Immunomodulator.

Table 5 Multivariate analysis of risk factors for active tuberculosis infection after anti-TNF therapy

	OR	95%CI	P value
Age at anti-TNF	0.98	0.94-1.02	0.346
Female	1.95	0.53-7.18	0.328
LTBI	5.76	1.57-21.20	0.008
WBC count < 5000 mm3	4.50	1.51-13.44	0.007

LTBI: Latent tuberculosis infection; WBC: White blood cell.