Predictors of bowel damage in the long-term progression of Crohn’s disease

Table 1 Baseline demographic and clinical characteristics of patients, n (%)

Variable	n = 72
Female sex	42 (58.3)
Age at inclusion in yr, mean (SD)	34.41 (± 11.1)
Age at diagnosis in yr
< 16	8 (11.1)
17-40	57 (79.2)
> 40	7 (9.7)
Disease duration in yr, mean (SD)	8.09 (± 7.3)
Disease duration in yr
< 2	21 (29.2)
2-10	31 (43.1)
>10	20 (27.8)
Smoking status
Never smoker	28 (38.9)
Current smoker	31 (43.1)
Past smoker	13 (18.1)
CD location
Terminal ileum	27 (37.5)
Colon	8 (11.1)
Ileocolic	37 (51.4)
CD upper tract involvement	6 (8.3)
CD phenotype
Inflammatory	30 (41.7)
Stricturing	15 (20.8)
Penetrating	14 (19.4)
Stricturing and penetrating	13 (18.1)
Current or past history of perianal disease	14 (19.4)
Family history	5 (6.9)
Previous resective surgery
No	51 (70.8)
1 surgery	13 (18.1)
> 1 surgery	8 (11.1)
Biological naïve at baseline
Yes	46 (63.9)
No	26 (36.1)
Treatment at baseline
None	18 (25.0)
Corticosteroids	4 (5.6)
Immunosuppressants	32 (44.4)
TNF-α inhibitors	8 (11.1)
Immunosuppressants plus TNF-α inhibitors	10 (13.9)
CRP in mg/L, mean (SD)	2.89 (± 4.2)
CRP
Normal: < 1 mg/L	30 (41.7)
Elevated: ≥ 1 mg/L	42 (58.3)
CDAI, mean (SD)	194.73 (± 95.8)
Clinical activity according to CDAI score
Active disease	51 (69.9)
Clinical remission	21 (28.8)
CDEIS, mean (SD)	7.8 (± 6.7)
CDEIS
< 3.5	20 (29.9)
3.5-7.0	18 (26.8)
> 7.0	29 (43.3)
NA	5

CD: Crohn’s disease; CDAI: Crohn’s disease Activity Index; CDEIS: Crohn’s disease Endoscopic Index of Severity; CRP: C-reactive protein; SD: Standard deviation; TNF: Tumor necrosis factor.

Table 2 Evaluation of the Lémann index score at baseline, at second assessment, and changes over time

Parameter	LI at baseline	LI at second assessment	Changes in LI
Global Lémann index	5.75 ± 7.57	7.26 ± 9.04	1.51 ± 6.51 (P = 0.054)
Organ location
Upper digestive tract	0.03 ± 0.18	0.04 ± 0.35	0.01 ± 0.33 (P = 0.721)
Small bowel damage score	1.79 ± 1.62	2.46 ± 2.51	0.67 ± 1.75 (P = 0.002)
Colon/rectum damage score	3.19 ± 3.94	3.39 ± 3.81	0.2 ± 3.38 (P = 0.622)
Anus damage score	0.80 ± 4.32	1.38 ± 5.95	0.58 ± 4.28 (P = 0.253)
LI subscales
Stricturing subscale	1.12 ± 1.38	0.88 ± 1.44	-0.24 ± 1.77 (P = 0.262)
Fistulizing subscale	1.95 ± 2.39	1.01 ± 1.99	-0.94 ± 2.19 (P = 0.001)
Surgery subscale	2.72 ± 6.78	5.32 ± 8.52	2.60 ± 5.82 (P = 0.001)

Data are presented as mean ± SD. LI: Lémann index.

Table 3 Demographics and Crohn’s disease characteristics associated with the Lémann index progression, n (%)

	LI progression, n = 38	No LI progression, n = 34	P value
Sex			0.352
Male	18 (60.0)	12 (40.0)
Female	20 (47.6)	22 (52.4)
Age at diagnosis in yr			0.961
< 16	4 (50.0)	4 (50.0)
17-40	30 (52.6)	27 (47.4)
> 40	4 (57.1)	3 (42.9)
Age at baseline, mean (SD)	25.17 (± 10.4)	27.61 (± 10.3)	0.323
CD location at baseline			0.091
Terminal ileum	17 (66.6)	9 (33.3)
Colon	2 (25.0)	6 (75.0)
Ileocolic	18 (48.7)	19 (51.3)
CD upper tract involvement			0.677
Yes	4 (66.7)	2 (33.3)
No	34 (51.5)	32 (48.5)
CD phenotype at baseline			0.001
Inflammatory	7 (23.3)	23 (76.7)
Stricturing	12 (80.0)	3 (20.0)
Penetrating	10 (71.4)	4 (28.6)
Stricturing and penetrating	9 (69.2)	4 (30.8)
Current or past history of perianal disease at baseline			0.151
Yes	10 (71.4)	4 (28.6)
No	28 (48.3)	30 (51.7)
Disease duration at inclusion, mean (SD)	10.36 (± 8.4)	5.54 (± 4.8)	0.001
Disease duration at inclusion in yr			0.001
< 2	8 (38.1)	13 (61.9)
2-10	14 (45.2)	17 (54.8)
>10	16 (80.0)	4 (20.0)
Smoking status			0.342
Never smoker	15 (53.6)	13 (46.4)
Current smoker	14 (45.2)	17 (54.8)
Past smoker	9 (69.2)	4 (30.8)
Family history			0.541
Yes	2 (40.0)	3 (60.0)
No	35 (53.0)	31 (47.0)
Immunosuppressant treatment between intervals			0.741
Yes	35 (52.2)	32 (47.8)
No	3 (40.0)	2 (60.0)
Biological naïve at baseline			0.143
Yes	21 (45.7)	25 (54.3)
No	17 (65.4)	9 (34.6)
Biological treatment between intervals			0.591
Yes	34 (54.0)	29 (46.0)
No	4 (44.4)	5 (55.6)
Biological treatment between intervals	21 (47.7)	23 (52.3)	0.443
TNF-α inhibitors	8 (61.5)	5 (38.5)
TNF-α inhibitors and ustekinumab	2 (66.7)	1 (33.3)
TNF-α inhibitors and vedolizumab	2 (100.0)	0 (0)
TNF-α inhibitors, vedolizumab and ustekinumab	1 (100.0)	0 (0)
Previous surgery at inclusion			0.192
Yes	14 (66.7)	7 (33.3)
No	24 (47.1)	27 (52.9)
Autologous stem-cell transplantation between intervals			0.602
Yes	2 (66.7)	1 (33.3)
No	36 (52.2)	33 (47.8)
Surgery between intervals			0.001
Yes	23 (95.8)	1 (4.2)
No	15 (31.3)	33 (68.8)
Baseline LI score evaluation, mean (SD)
Total LI score	5.60 (± 4.40)	5.90 (± 10.10)	0.860
Upper tract score	0.05 (± 0.30)	0	0.211
Small bowel score	2.16 (± 1.60)	1.37 (± 1.60)	0.040
Colon/rectum score	2.98 (± 3.00)	3.42 (± 4.80)	0.652
Anus score	0.51 (± 1.90)	1.13 (± 6.00)	0.542
Stricturing score	1.43 (± 1.60)	0.78 (± 1.00)	0.045
Fistulizing score	1.69 (± 2.50)	2.23 (± 2.30)	0.341
Surgical score	2.54 (± 3.40)	2.92 (± 9.30)	0.823
CRP at baseline, mean (SD)	2.93 (± 4.70)	2.84 (± 3.60)	0.921
CRP at baseline			0.692
Normal: < 1 mg/L	15 (50.0)	15 (50.0)
Elevated: ≥ 1 mg/L	23 (54.8)	19 (45.2)
CDAI, mean (SD)	199.69 (± 94.9)	189.19 (± 97.8)	0.673
Clinical activity at baseline according to CDAI score			0.610
Active disease	28 (54.9)	23 (45.1)
Clinical remission	10 (47.6)	11 (52.4)
CDEIS activity at baseline, mean (SD)	6.2 (5.4)	9.44 (1.3)	0.052
CDEIS activity at baseline			0.190
< 3.5	12 (60.0)	8 (20.0)
3.5-7.0	11 (61.1)	7 (38.9)
> 7.0	11(37.9)	18 (62.1)

CRP: C-reactive protein; CD: Crohn’s disease; CDAI: Crohn’s disease Activity Index; CDEIS: Crohn’s disease Endoscopic Index of Severity; LI: Lémann index; SD: Standard deviation; TNF; Tumor necrosis factor.

Table 4 Multivariate analysis for significant bowel damage progression

Risk factor	OR	95%CI	P value
CD location
Terminal ileum	8.307	1.296-53.251	0.026
Colon	0.580	0.014-24.658	0.776
CD phenotype
Stricturing	18.447	2.219-153.321	0.007
Fistulizing	17.085	2.217-131.673	0.006
Stricturing and fistulizing	12.296	1.190-127.022	0.035
Disease duration at inclusion in yr
2-10	2.174	0.374-12.652	0.387
> 10	15.196	1.557-148.332	0.019
Baseline LI stricturing score	1.929	1.004-3.709	0.049
Baseline LI small bowel score	0.690	0.383-1.243	0.216
CDEIS activity at baseline	0.948	0.837-1.074	0.400

95%CI: 95% confidence interval; CD: Crohn’s disease; CDEIS: Crohn’s Disease Endoscopic Index of Severity; LI: Lémann index; OR: Odds ratio.