Two-year delay in ulcerative colitis diagnosis is associated with anti-tumor necrosis factor alpha use

Table 1 Baseline characteristics of patients (n = 551)

Characteristics	Value
Male sex (%)	318/551 (55.7)
Age at diagnosis, yr	40.56 ± 16.11
BMI at diagnosis, kg/m2	22.28 ± 3.19
Family history of IBD (%)	51/369 (13.8)
History of smoking (%)	77/443 (17.4)
First symptom
Hematochezia	388/548 (70.8)
Diarrhea	164/548 (29.9)
Abdominal pain	39/548 (7.1)
Diagnostic interval, d (median)	223.28 ± 483.15 (69)
Time from first symptom to hospital visit, d (median)	154.22 ± 379.140 (40)
Time from first hospital visit to diagnosis, d (median)	69.06 ± 295.04 (9)
Mayo score at diagnosis (%)
Mild	179/399 (44.9)
Moderate	204/399 (51.1)
Severe	220/399 (4.0)
Disease extent at diagnosis (%)
Proctitis	253/547 (46.3)
Left side	160/547 (29.3)
Extensive	134/547 (24.5)
Steroid (oral or intravenous) use (%)	250/551 (45.4)
AZA/6MP use (%)	163/551 (29.6)
Anti-TNFα use (%)	50/551 (9.1)
Admission due to flare-up (%)	121/430 (22.0)
Frequent admission due to flare-up (%)	50/551 (9.1)
UC-related surgery (%)	7/551 (1.3)
Clinical remission at the latest follow-up (%)	333/467 (71.3)

BMI: Body mass index; IBD: Inflammatory bowel disease; AZA/6MP: Azathioprine or 6-mercaptopurine; Anti-TNFα: Anti-tumor necrosis factor alpha; UC: Ulcerative colitis.

Table 2 Diagnostic delay and prognosis

Diag-nostic inter-val	3 mo			6 mo			12 mo			18 mo			24 mo
	Early group (%)	Delay group (%)	P value	Early group (%)	Delay group (%)	P value	Early group (%)	Delay group (%)	P value	Early group (%)	Delay group (%)	P value	Early group (%)	Delay group (%)	P value
	322	229		401	150		452	99		496	55		509	42
	(58.4)	(41.6)		(72.8)	(27.2)		(82.0)	(18)		(90)	(10)		(92.4)	(7.6)
Anti-TNFα use			0.150			0.249			0.847			0.137			0.019
No	288	213		361	140		410	91		454	47		467	34
	(89.4)	(93.0)		(90.0)	(93.3)		(90.7)	(91.9)		(91.5)	(85.5)		(91.7)	(81.0)
Yes	34	16		40	10		42	8		42	8		42	8
	(10.6)	(7.0)		(10.0)	(6.7)		(9.3)	(8.1)		(8.5)	(14.5)		(8.3)	(19.0)
Admission (flare-up)			0.269			0.203			1.000			0.509			0.703
No	246	184		307	123		353	77		389	41		398	32
	(76.4)	(80.3)		(76.6)	(82.0)		(78.1)	(77.8)		(78.4)	(74.5)		(78.2)	(76.2)
Yes	76	45		94	27		99	22		107	14		111	10
	(23.6)	(19.7)		(23.4)	(18.0)		(21.9)	(22.2)		(21.8)	(25.5)		(21.8)	(23.8)
Frequent admission			0.150			0.384			0.443			0.806			0.412
No	288	213		362	139		409	92		450	51		461	40
	(89.4)	(93.0)		(90.3)	(92.7)		(90.5)	(92.9)		(90.7)	(92.7)		(90.6)	(95.2)
Yes	34	16		39	11		43	7		46	4		48	2
	(10.6)	(7.0)		(9.7)	(7.3)		(9.5)	(7.1)		(9.3)	(7.3)		(9.4)	(4.8)
Surgery-related UC			0.457			0.092			0.114			0.523			0.428
No	319	225		398	146		448	96		490	54		503	41
	(99.1)	(98.3)		(99.3)	(97.3)		(99.1)	(97.7)		(98.8)	(98.2)		(98.8)	(97.6)
Yes	3	4		3	4		4	3		6	1		6	1
	(0.9)	(1.7)		(0.7)	(2.7)		(0.9)	(3.0)		(1.2)	(1.8)		(1.2)	(2.4)
Clinical remission			0.866			0.842			0.509			0.679			0.338
No	191	142		97	37		267	66		300	33		310	23
	(71.0)	(71.7)		(29.0)	(28.0)		(70.6)	(74.2)		(71.6)	(68.8)		(71.9)	(63.9)
Yes	78	56		238	95		111	23		119	15		121	13
	(29.0)	(28.3)		(71.0)	(72.0)		(29.4)	(25.8)		(28.4)	(31.3)		(28.1)	(36.1)

The early group was defined as receiving a diagnosis earlier than the diagnostic interval, and the delay group was defined as receiving a later diagnosis. Clinical remission was investigated in 467 patients. And the proportion of the delay group in 467 patients was similar to that of 551 patients: 3 mo (42.3%), 6 mo (28.2%), 12 mo (19%), 18 mo (9.6%) and 24 mo (7.7%). Anti-TNFα: Anti-tumor necrosis factor alpha; UC: Ulcerative colitis.

Table 3 Comparisons of clinical characteristics between the early and delay groups according to the 24-mo diagnostic interval for patients with ulcerative colitis

		Total	Early group (< 24 mo)	Delay group (≥ 24 mo)	P value
Sex (%)					0.872
	Male	318 (57.7)	293 (57.6)	25 (59.5)
	Female	233 (42.3)	216 (42.4)	17 (40.5)
Age (%)		40.56 ± 16.11	40.93 ± 16.20	41.21 ± 14.47	0.903
					0.020
	≥ 60 yr	80 (14.5)	79 (15.5)	1 (2.4)
	< 60 yr	471 (85.5)	430 (84.5)	41 (97.6)
BMI (%)					0.306
	< 25 kg/m2	295 (83.3)	268 (82.7)	27 (90.0)
	≥ 25 kg/m2	59 (16.7)	56 (17.3)	3 (10.0)
Education (%)					0.561
	< University	170 (56.5)	152 (55.9)	18 (62.1)
	≥ University	131 (43.5)	120 (44.1)	11 (37.9)
Residence at diagnosis (%)					0.498
	Rural	503 (94.2)	466 (94.3)	37 (92.5)
	Urban	31 (5.8)	28 (5.7)	3 (7.5)
Family history of IBD (%)					0.782
	No	318 (86.2)	291 (85.8)	27 (90.0)
	Yes	51 (13.8)	48 (14.2)	3 (10.0)
Smoking (%)					0.008
	No	366 (82.6)	339 (84.1)	27 (67.5)
	Yes	77 (17.4)	64 (15.9)	13 (32.5)
First symptom (%)
					0.540
Hematochezia	No	160 (29.2)	146 (28.9)	14 (33.3)
	Yes	388 (70.8)	360 (71.1)	28 (66.7)
					0.229
Chronic diarrhea	No	384 (70.1)	358 (70.8)	26 (61.9)
	Yes	164 (29.9)	148 (29.2)	16 (38.1)
Diagnosis before UC
					0.000
Hemorrhoids (%)	No	487 (94.7)	453 (95.8)	34 (82.9)
	Yes	27 (5.3)	20 (4.2)	7 (17.1)
					0.066
IBS (%)	No	494 (96.1)	457 (96.6)	37 (90.2)
	Yes	20 (3.9)	16 (3.4)	4 (9.8)
Mayo score at diagnosis (%)					0.958
	Mild	179 (44.9)	163 (44.9)	16 (44.4)
	Moderate + Severe	220 (55.1)	200 (55.1)	20 (55.6)
Disease extent at diagnosis (%)					0.914
	Proctitis + left side	413 (75.5))	381 (75.4)	32 (76.2)
	Extensive	134 (24.5)	124 (24.6)	10 (23.8)

BMI: Body mass index; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; IBS: Irritable bowel syndrome.

Table 4 Risk factors predictive of 24-mo diagnostic delay according to the univariate and multivariate analyses

	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)	P value
Age (≥ 60 yr vs < 60 yr)	7.533 (1.021-55.557)	0.020	14.778 (1.731-126.121)	0.014
Smoking history (no vs yes)	2.550 (1.249-5.206)	0.008	2.688 (1.239-5.747)	0.012
Misdiagnosed as hemorrhoids (no vs yes)	4.663 (1.842-11.803)	0.000	11.066 (3.596-34.053)	0.000

OR: Odd ratio; CI: Confidence interval.

Table 5 Risk factors related to anti-tumor necrosis factor alpha use

		Total	Anti-TNFα No	Anti-TNFα Yes	P value
Sex (%)					0.731
	Male	318 (57.7)	288 (57.5)	30 (60.0)
	Female	233 (42.3)	213 (42.5)	20 (40.0)
Age (%)		40.56 ± 16.11	41.10 ± 16.76	38.36 ± 16.05	0.268
					0.913
	< 60 yr	278 (50.5)	428 (85.4)	43 (86.0)
	≥ 60 yr	273 (49.5)	73 (14.6)	7 (14.0)
Smoking (%)					0.422
	No	366 (82.6)	329 (83.1)	37 (78.7)
	Yes	77 (17.4)	67 (16.9)	10 (21.3)
BMI (%)					0.667
	< 25 kg/m2	295 (83.3)	260 (83.6)	35 (81.4)
	≥ 25 kg/m2	59 (16.7)	51 (16.4)	8 (18.6)
Mayo score at diagnosis (%)					0.001
	Mild	179 (44.9)	170 (47.6)	9 (21.4)
	Moderate + severe	220 (55.1)	187 (52.4)	33 (78.6)
Disease extent at diagnosis (%)					0.000
	Proctitis + left side	413 (75.5)	394 (79.3)	19 (38.0)
	Extensive	134 (24.5)	103 (20.7)	31 (62.0)
CRP level at diagnosis (%)					0.536
	< 5 mg/dL	265 (79.3)	17 (73.9)	282 (79.0)
	≥ 5 mg/dL	69 (20.7)	6 (26.1)	75 (21.0)
Steroid use after diagnosis					0.269
	< 2 mo		116 (57.1)	31 (66.0)
	≥ 2 mo		87 (42.9)	16 (34.0)
AZA/6MP use after diagnosis					0.741
	< 2 mo	47 (29.2)	37 (29.8)	10 (27.0)
	≥ 2 mo	114 (70.8)	87 (70.2)	27 (73.0)
Diagnostic delay (%)					0.019
	< 24 mo	509 (92.4)	467 (93.2)	42 (84.0)
	≥ 24 mo	42 (7.6)	34 (6.8)	8 (16.0)

Anti-TNFα: Anti-tumor necrosis factor alpha; BMI: Body mass index; AZA/6MP: Azathioprine or 6-mercaptopurine.

Table 6 Risk factors predictive of anti-tumor necrosis factor alpha use according to the univariate and multivariate analyses

	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)	P value
Mayo score (mild vs moderate + severe).	3.333 (1.550-7.169)	0.002	2.168 (0.956-4.916)	0.064
Disease extent (proctitis + left side vs extensive)	6.241 (3.388-11.496)	0.000	3.768 (1.860-7.632)	0.000
Diagnostic delay (< 24 mo vs ≥ 24 mo)	2.616 (1.138-6.014)	0.019	2.599 (1.006-4.916)	0.049

OR: Odd ratio; CI: Confidence interval.