Effectiveness of ustekinumab in postoperative Crohn's disease management: Evidence from a Chinese multicenter cohort

Table 1 Baseline characteristics of patients with postoperative Crohn's disease treated with ustekinumab (n = 71)

Characteristic	Overall (n = 71)	First-line UST (n = 45)	Second-line UST (n = 26)	P value
Demographics
Age (years)	35.4 ± 11.8	34.2 ± 11.0	37.5 ± 12.9	0.260
Male sex	53 (74.6)	35 (77.8)	18 (69.2)	0.425
Occupation				0.763
Employee	35 (49.3)	22 (48.9)	13 (50.0)
Student	11 (15.5)	8 (17.8)	3 (11.5)
Unemployed	25 (35.2)	15 (33.3)	10 (38.5)
Comorbidities
Tuberculosis history	10 (14.1)	8 (17.8)	2 (7.7)	0.209
Hepatitis B history	3 (4.2)	3 (6.7)	0 (0.0)	0.248
Cancer history	2 (2.8)	1 (2.2)	1 (3.8)	0.690
Disease characteristics
Disease duration (years)	5.0 (2.0-10.0)	4.0 (2.0-6.0)	9.5 (5.3-17.0)	< 0.001
Montreal age classification				0.916
A1 (≤ 16 years)1	7 (9.9)	4 (8.9)	3 (11.5)
A2 (17-40 years)	51 (71.8)	33 (73.3)	18 (69.2)
A3 (> 40 years)	13 (18.3)	8 (17.8)	5 (19.2)
Montreal location				0.045
L1 (ileal)	21 (29.6)	9 (20.0)	12 (46.2)
L2 (colonic)	7 (9.9)	4 (8.9)	3 (11.5)
L3 (ileocolonic)	43 (60.6)	32 (71.1)	11 (42.3)
L4 (upper GI)	0 (0.0)	0 (0.0)	0 (0.0)
Montreal behavior				0.727
B1 (non-stricturing, non-penetrating)	6 (8.5)	3 (6.7)	11 (24.4)
B2 (stricturing)	47 (66.2)	31 (68.9)	16 (61.5)
B3 (penetrating)	18 (25.4)	11 (24.4)	7 (26.9)
Perianal disease	24 (33.8)	16 (35.6)	8 (30.8)	0.681
Extraintestinal manifestations	8 (11.3)	2 (4.4)	6 (23.1)	0.024
Smoking history	9 (12.7)	8 (17.8)	1 (3.8)	0.087
Alcohol history	4 (5.6)	4 (8.9)	0 (0.0)	0.153
History of biologic use
Previous biologic exposure				< 0.001
None	41 (57.7)	40 (88.9)	1 (3.8)
Infliximab only	20 (28.2)	4 (8.9)2	16 (61.5)
Adalimumab only	3 (4.2)	0 (0.0)	3 (11.5)
Infliximab and adalimumab	4 (5.6)	1 (2.2)2	3 (11.5)
Infliximab and vedolizumab	2 (2.8)	0 (0)	2 (7.7)
Infliximab, adalimumab and vedolizumab	1 (1.4)	0 (0.0)	1 (2.8)
Treatment timing				< 0.001
Time from surgery to UST (months)	1.0 (1.0-17.0)	2.0 (1.0-6.0)	16.5 (6.0-36.0)

¹The “A1” classification in the Montreal system refers to the “age at diagnosis” (≤ 16 years), not the patient’s age at enrollment. These seven patients were diagnosed with Crohn's disease during childhood but were adults (≥ 18 years) when they were enrolled in this study for ustekinumab treatment.

²Five patients in the first-line group had exposure to infliximab prior to surgery but received ustekinumab as their first biologic agent during the postoperative period.

Continuous variables are presented as mean ± SD, and non-continuous variables are presented as medians (quartile). Categorical variables are presented as n (%). P values from t-test, χ² test, Fisher's exact tests or non-parametric tests, as appropriate. UST: Ustekinumab; GI: Gastrointestinal.

Table 2 Efficacy outcomes before and after ustekinumab treatment (n = 71)

Parameter	First-line group (n = 45)		Second-line group (n = 26)		P value4
	Before UST	After UST	Before UST	After UST
Clinical outcomes
HBI score	5.6 ± 3.0	1.8 ± 1.5	5.2 ± 2.5	2.8 ± 2.0	0.019
P value1		< 0.001		< 0.001
Active disease2	32 (71.1)	2 (4.4)	19 (73.1)	4 (15.4)	0.110
P value1		< 0.001		< 0.001
Endoscopic outcomes
Rutgeerts score	2.7 ± 1.1	0.9 ± 1.1	2.7 ± 1.0	1.4 ± 1.1	0.039
P value1		< 0.001		< 0.001
Endoscopic improvement3	N/A	39 (86.7)	N/A	19 (73.1)	0.154
Endoscopic remission (< i2)	N/A	35 (77.8)	N/A	15 (57.7)	0.074
BMI (kg/m2)	18.7 ± 2.8	20.1 ± 3.0	20.7 ± 4.2	21.8 ± 3.7	0.037
P value1		< 0.001		0.003
Laboratory parameters
CRP (mg/L)	7.1 ± 9.2	3.7 ± 3.8	7.8 ± 11.1	4.6 ± 4.0	0.378
P value1		0.008		0.152
ESR (mm/hour)	20.2 ± 16.7	12.3 ± 13.7	19.1 ± 18.1	13.3 ± 17.2	0.558
P value1		0.005		0.124
Albumin (g/L)	40.2 ± 14.7	43.7 ± 14.6	40.7 ± 4.0	41.2 ± 3.6	0.438
P value1		< 0.001		0.615
Hemoglobin (g/L)	110.5 ± 21.8	125.2 ± 21.9	119.1 ± 21.1	125.2 ± 25.8	0.734
P value1		< 0.001		0.088
Fecal occult blood positive	29 (64.4)	9 (20.0)	14 (53.8)	8 (30.8)	0.306
P value1		< 0.001		0.092

¹Paired t-test or McNemar test comparing week 24 to the baseline within each group.

²Active disease: Harvey-Bradshaw Index > 4.

³Endoscopic improvement was defined as a decrease in the Rutgeerts score of ≥ 1 point.

⁴Comparison refers to the difference between the first-line and second-line groups at week 24 (or the rate of response) using independent t-tests or χ² tests.

Data are presented as mean ± SD for continuous variables or n (%) for categorical variables. UST: Ustekinumab; HBI: Harvey-Bradshaw Index; BMI: Body mass index; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; N/A: Not applicable.

Table 3 Multivariate generalized estimation equations analysis of factors associated with a Rutgeerts score improvement (n = 71)

Variable	β	Robust SE	Wald χ²	OR (95%CI)	P value
Intercept	-3.709	1.351	7.532	0.025 (0.002-0.346)	0.006
Treatment line
First-line UST therapy (vs second-line)	0.546	0.258	4.498	1.727 (1.042-2.862)	0.034
Montreal classification
Age A2 (17-40 years) vs A1 (≤ 16 years)	2.411	1.122	4.621	11.149 (1.237-100.482)	0.032
Age A3 (> 40 years) vs A1 (≤ 16 years)	1.083	0.301	12.927	2.953 (1.637-5.329)	< 0.001
Location L2 (colonic) vs L1 (ileal)	1.171	1.014	1.334	3.225 (0.442-23.527)	0.248
Location L3 (ileocolonic) vs L1 (ileal)	1.342	1.022	1.725	3.827 (0.517-28.348)	0.189
Behavior B2 (stricturing) vs B1 (non-stricturing, non-penetrating)	1.325	0.661	4.023	3.764 (1.031-13.742)	0.045
Behavior B3 (penetrating) vs B1 (non-stricturing, non-penetrating)	2.459	1.203	4.179	11.692 (1.107-123.521)	0.041
Perianal disease (yes vs no)	-1.208	1.165	1.074	0.299 (0.030-2.934)	0.300
Other clinical factors
Extraintestinal manifestations (yes vs no)	0.613	0.459	1.783	1.847 (0.750-4.544)	0.182
Disease duration (years)	-0.021	0.007	10.431	0.979 (0.967-0.992)	0.001
Pre-UST Rutgeerts score	0.607	0.331	3.369	1.835 (0.960-3.509)	0.066

Model information: (1) Dependent variable: Rutgeerts score improvement (0 = no, 1 = yes); (2) Analysis method: Generalized estimating equations; and (3) Reference categories: Second-line, Age A1, location L1, behavior B1, no perianal disease and no extraintestinal manifestations. UST: Ustekinumab.