Risk factors and fatigue in difficult-to-treat Crohn’s disease: A cross-sectional study of a Chinese cohort

Table 1 Characteristics of patients with difficult-to-treat Crohn’s disease and non difficult-to-treat Crohn’s disease, n (%)/mean ± SD/ median (interquartile range)

Characteristics	DTT-CD (n = 90)	Non DTT-CD (n = 85)	P value
Age	32.00 (25.00-42.00)	34.00 (23.75-46.00)
Gender
Male	68 (75.6)	55 (64.7)
Female	22 (24.4)	30 (35.3)
Disease duration (years)	6.85 ± 5.70	5.23 ± 5.43	0.057
Disease activity
Active	22 (24.4)	35 (41.2)
Remission	68 (75.6)	50 (58.8)
Anal fistula
(+)	85 (94.4)	53 (62.4)
(-)	5 (5.6)	32 (37.6)
Surgical history
(+)	54 (60.0)	32 (37.6)
(-)	36 (40.0)	53 (62.4)
Age at diagnosis (years)
< 17	5 (5.6)	5 (5.9)
17-40	72 (80.0)	60 (70.9)
> 40	13 (14.4)	20 (23.5)
Behavior
B1	34 (37.8)	27 (31.8)
B2	39 (43.3)	43 (50.6)
B3	11 (12.2)	6 (7.1)
B2 + B3	6 (6.7)	9 (10.6)
Location
L1	20 (22.2)	29 (34.1)
L1 + L4	7 (7.8)	3 (3.6)
L2	3 (3.3)	5 (5.9)
L2 + L4	1 (1.1)	3 (3.5)
L3	49 (54.4)	37 (43.5)
L3 + L4	9 (10.0)	6 (7.1)
L4	0 (0)	2 (2.4)
Number of biologics or small molecule
0	10 (11.1)	27 (31.8)
1	37 (41.1)	58 (68.2)
2	39 (43.3)	NA
3	4 (4.4)	NA
IL (pg/mL)
IL-5	1.13 ± 0.71	0.86 ± 0.54	0.005
IL-10	3.35 (2.64-4.77)	3.32 ± 1.47	0.099
Hemoglobin (g/L)	142.00 (126.00-150.00)	132.00 (115.75-147.00)	0.011
Multidimensional Fatigue Inventory total scores	52.56 ± 13.57	50.71 ± 12.96
General fatigue	11.16 ± 3.49	10.90 ± 3.66
Physical fatigue	11.62 ± 3.78	12.00 (9.00-15.00)
Mental fatigue	10.00 (7.00-12.00)	9.00 (6.00-11.00)	0.032
Reduced activity	11.32 ± 3.14	11.00 (9.00-12.25)
Reduced motivation	8.00 (6.00-11.00)	8.00 (7.00-10.00)

Normally distributed data are expressed as mean ± SD, with P values derived from Student’s t-test or analysis of variance; non-normally distributed data are expressed as median with interquartile range, with P values derived from the Mann-Whitney U test or the Kruskal-Wallis test, respectively. Anal fistula: (1) (+) previous simple or complex anal fistula; and (2) (-) without any anal fistula or perianal disease. Surgical history: (1) (+): Crohn’s disease-related surgery; and (2) (-): Without any Crohn’s disease-related surgery. Number of biologics or small molecule with different mechanism: (1) Anti-tumor necrosis factor (infliximab, adalimumab); (2) Integrin receptor antagonist (vedolizumab); (3) Interleukin antagonist (ustekinumab); and (4) Janus kinase inhibitor (tofacitinib)[18]. CD: Crohn’s disease; DTT: Difficult-to-treat; IL: Interleukin; NA: Not available.

Table 2 Multivariable logistic regression analysis of risk factors for difficult-to-treat Crohn’s disease

Characteristics	Exp(B)	Lower 95%CI	Upper 95%CI	P value
Age at diagnosis
A2	1.568	0.328	7.500	0.574
A3	0.796	0.136	4.674	0.801
Disease behavior
B2	0.560	0.238	1.321	0.186
B3	0.908	0.213	3.874	0.896
B2 + B3	3.042	0.676	13.692	0.147
Disease location
L2	0.473	0.079	2.843	0.414
L3	1.762	0.765	4.060	0.183
L4	0.000	0.000	0.000	0.999
L1 + L4	6.443	1.011	41.081	0.049
L2 + L4	0.344	0.018	6.387	0.474
L3 + L4	2.882	0.743	11.187	0.126
IL-5	2.715	1.457	5.058	0.002
IL-10	1.234	1.005	1.515	0.045
Hemoglobin	1.025	1.005	1.047	0.016
Disease duration	1.097	1.017	1.182	0.016
Enteral nutrition
Total enteral nutrition	1.538	0.52	4.542	0.436
Partial enteral nutrition	2.940	1.209	7.153	0.017

The analysis was conducted on data from 168 Crohn’s disease patients (seven patients were excluded due to incomplete data). IL: Interleukin.

Table 3 Results of a multivariable logistic regression analysis examining risk factors for difficult-to-treat Crohn’s disease

Characteristics	Exp(B)	Lower 95%CI	Upper 95%CI	P value
Age at diagnosis
A2	1.652	0.342	7.985	0.532
A3	0.869	0.145	5.205	0.878
Disease behavior
B2	0.566	0.239	1.339	0.196
B3	0.822	0.19	3.546	0.792
B2 + B3	3.502	0.753	16.277	0.110
Disease location
L2	0.510	0.083	3.120	0.466
L3	1.863	0.797	4.352	0.151
L4	0.000	0.000	0.000	0.999
L1 + L4	6.032	0.954	38.135	0.056
L2 + L4	0.398	0.02	7.912	0.546
L3 + L4	2.965	0.744	11.808	0.123
IL-5	2.656	1.421	4.964	0.002
IL-10	1.255	1.011	1.558	0.04
Hemoglobin	1.023	1.002	1.045	0.035
Disease duration	1.096	1.016	1.182	0.018
Enteral nutrition
Total enteral nutrition	1.591	0.534	4.742	0.404
Partial enteral nutrition	2.858	1.165	7.014	0.022
Disease activity	0.621	0.271	1.423	0.261

The model adjusted for disease activity and was based on data from 168 patients (from an initial cohort of 175; 7 exclusions due to incomplete data). IL: Interleukin.

Table 4 Multiplevariable linear regression analysis of factors associated with fatigue in difficult-to-treat Crohn’s disease patients

Characteristics	Total scores		General fatigue		Physical fatigue		Mental fatigue		Reduced activity		Reduced motivation
	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value
Partial enteral nutrition	7.023 (0.240-13.806)	0.043	2.286 (0.534-4.038)	0.011	2.087 (0.296-3.877)	0.033	-	-	-	-	1.955 (0.358-3.552)	0.017
A3	14.328 (1.552-27.103)	0.029	-	-	3.806 (0.407-7.206)	0.029	-	-	-	-	3.385 (0.451-6.320)	0.024
B2	-	-	-	-	-	-	-	-	-	-	-1.816 (-3.342 to -0.289)	0.02
B3	-	-	-	-	-	-	-	-	-	-	-2.810 (-5.099 to -0.520)	0.017
Surgical history	-	-	-	-	-	-	-	-	1.621 (0.210-3.033)	0.025	-	-
Disease activity	-	-	-	-	2.540 (0.531-4.549)	0.014	-	-	-	-	-	-
	n = 88		n = 90		n = 88		n = 88		n = 88		n = 88

Variable in the model: (1) C-reactive protein; (2) Vitamin B12; (3) Hemoglobin; (4) Ca; (5) Fe; (6) Partial enteral nutrition; (7) Total enteral nutrition; (8) B2; (9) B3; (10) B2 + B3; (11) A2; (12) A3; (13) L2; (14) L3; (15) L1 + L4; (16) L2 + L4; (17) L3 + L4; and (18) Disease activity. Only statistically significant associations (P < 0.05) are shown in detail.

Table 5 Association between difficult-to-treat characteristics at diagnosis and fatigue in a cohort of patients with Crohn’s disease: A multiple linear regression analysis

Characteristics	Total scores		General fatigue		Physical fatigue		Mental fatigue		Reduced activity		Reduced motivation
	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value	Coefficient (95%CI)	P value
Fistula	-	-	-	-	-	-	-	-	-	-	-	-
Number of biologics	-	-	-	-	-	-	-	-	-	-	-	-
Disease activity	8.535 (4.225-12.846)	0.000	2.041 (0.878-3.205)	0.001	2.314 (1.080-3.549)	0.000	-	-	1.765 (0.830-2.699)	0.000	1.326 (0367-2.284)	0.007
Surgical history	-	-	-	-	-	-	-	-	1.765 (0.830-2.699)	0.012	-	-
Disease duration	-	-	-	-	-	-	-	-	-	-	-	-
A2	-	-	2.677 (0.393-4.962)	0.022	-	-	-	-	-	-	-	-
A3	-	-	3.119 (0.557-5.681)	0.017	-	-	-	-	2.111 (0.054-4.167)	0.044	2.131 (0.022-4.241)	0.022
L3 + L4		-	-	-	-	-	-	-	1.647 (0.033-3.262)	0.046	-	-
L2 + L4	-	-	-	-	-	-	-	-	-	-	-	-
L1 + L4	-	-	-	-	-	-	-	-	-	-	-	-
L2	-	-	-	-	-	-	-	-	-	-	-	-
L3	-	-	-	-	-	-	-	-	-	-	-	-
L4	-	-	-	-	-	-	-	-	-	-	-	-
B2	-	-	-	-	-	-	-	-	-	-	-	-
B3	-	-	-	-	-	-	-	-	-	-	-	-
B2 + B3	-	-	-	-	-	-	-	-	-	-	-	-
Total	n = 175		n = 175		n = 175		n = 175		n = 175		n = 175

Variable in the model: (1) Fistula; (2) Number of biologics or small molecule with different mechanism; (3) Disease activity; (4) Surgery history; (5) Disease duration; (6) B2; (7) B3; (8) A2; (9) A3; (10) L2; (11) L3; (12) L4; (13) L1 + L4; (14) L2 + L4; and (15) L3 + L4. Fistula: Simple or complex anal fistula. Number of biologics or small molecule with different mechanism: (1) Anti-tumor necrosis factor (infliximab, adalimumab); (2) Integrin receptor antagonist (vedolizumab); (3) Interleukin antagonist (ustekinumab); and (4) Janus kinase inhibitor (tofacitinib)[18].