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Supplementary Table 1. Comparison of patients with and without fistula healing. ADA, adalimumab; IMM, immunomodulator; HBI, Harvey Bradshaw Index; CRP, C-reactive protein; FC, faecal calprotectin; ATA, antibodies to anti-TNF.

Adalimumab Patients with

fistula healing (n=21)

Patients without fistula healing

(n=14)

P-value

Median age, years (IQR) 31.6 (26.3-42.7) 33.9 (27.8-57.6) 0.33

Female gender, n (%) 8 (38.1) 9 (64.3) 0.13

Disease duration, years (IQR) 12.4 (8.9-20.6) 7.9 (5.2-15.7) 0.08

Complex perianal fistula, n (%)* 5 (23.8) 6 (42.9) 0.23

Median number of perianal procedures, n (IQR)

1 (1-3) 2 (1-3) 0.51

ADA duration, years (IQR) 2.8 (1.8-6.4) 2.5 (1.2-6.2) 0.76

Active smoking, n (%) 1 (4.8) 2 (14.3) 0.32

Concomitant antibiotics, n (%) 0 8 (57.1) <0.01

Concomitant IMM, n (%) 11 (52.4) 4 (28.6) 0.16

Median HBI (IQR) 3 (2-4) 6 (4-8) <0.01

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Median CRP, mg/L (IQR) 1.0 (1.0-6.5) 5.5 (3.0-14.0) 0.01 Median ADA level,µg/mL (IQR) 12.6 (10.1-16.2) 2.7 (0.0-7.2) <0.01

Presence of ATA, n (%) 1 (4.8) 6 (42.9) <0.01

*As per American Gastroenterological Association classification18

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Supplementary Table 2. Comparison of patients with and without fistula closure. ADA, adalimumab; IMM, immunomodulator; HBI, Harvey Bradshaw Index; CRP, C-reactive protein; FC, faecal calprotectin; ATA, antibodies to anti-TNF.

Adalimumab Patients with

fistula closure (n=15)

Patients without fistula closure

(n=20)

P-value

Median age, years (IQR) 34.7 (27.3-37.9) 30.5 (27.7-52.8) 0.86

Female gender, n (%) 4 (26.7) 13 (65.0) 0.03

Disease duration, years (IQR) 12.4 (9.5-20.7) 21.7 (17.9-34.3) <0.01

Complex perianal fistula, n (%)* 3 (20.0) 8 (40.0) 0.21

Median number of perianal procedures, n (IQR)

1 (1-3) 2 (1-3) 0.16

ADA duration, years (IQR) 2.8 (1.8-7.0) 2.5 (1.3-5.8) 0.98

Active smoking, n (%) 1 (6.7) 2 (10.0) 0.73

Concomitant antibiotics, n (%) 0 8 (40.0) <0.01

Concomitant IMM, n (%) 8 (53.3) 7 (35.0) 0.28

Median HBI (IQR) 3 (2-4) 5 (3-8) <0.01

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Median CRP, mg/L (IQR) 1.0 (1.0-7.0) 5.0 (3.3-14.0) 0.02 Median ADA level,µg/mL (IQR) 14.8 (11.0-16.3) 5.7 (0.0-10.4) <0.01

Presence of ATA, n (%) 1 (6.7) 6 (30.0) 0.09

*As per American Gastroenterological Association classification18

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Supplementary Table 3. Comparison of patients with and without fistula healing. IFX, infliximab; IMM, immunomodulator; HBI, Harvey Bradshaw Index; CRP, C-reactive protein;

ATA, antibodies to anti-TNF.

Infliximab Patients with

fistula healing (n=18)

Patients without fistula healing

(n=11)

P-value

Median age, years (IQR) 30.3 (26.0-51.0) 29.0 (21.3-36.3) 0.32

Female gender, n (%) 5 (27.8) 6 (54.5) 0.15

Disease duration, years (IQR) 6.4 (2.5-12.5) 1.9 (1.4-4.9) 0.16

Complex perianal fistula, n (%)* 8 (44.4%) 6 (54.5%) 0.60

Median number of perianal procedures, n (IQR)

1 (1-2) 3 (1-6) 0.05

IFX duration, years (IQR) 3.6 (1.2-5.8) 1.2 (0.9-1.4) 0.02

Active smoking, n (%) 3 (16.7) 1 (9.0) 0.57

Concomitant antibiotics, n (%) 0 3 (27.3) 0.02

Concomitant IMM, n (%) 9 (50.0) 8 (72.7) 0.23

Median HBI (IQR) 2 (1-3) 4 (3-6) <0.01

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Median CRP, mg/L (IQR) 2.0 (1.0-3.3) 6.0 (2.0-14.0) 0.02 Median IFX level,µg/mL (IQR) 8.1 (6.9-8.8) 3.2 (0.8-5.9) <0.01

Presence of ATA, n (%) 2 (11.1) 7 (63.6) <0.01

*As per American Gastroenterological Association classification18

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Supplementary Table 4. Comparison of patients with and without fistula closure. IFX, infliximab; IMM, immunomodulator; HBI, Harvey Bradshaw Index; CRP, C-reactive protein;

ATA, antibodies to anti-TNF.

Infliximab Patients with

fistula closure (n=16)

Patients without fistula closure

(n=13)

P-value

Median age, years (IQR) 30.3 (25.0-51.7) 30.0 (24.2-34.9) 0.42

Female gender, n (%) 5 (31.3) 6 (46.2) 0.41

Disease duration, years (IQR) 6.9 (1.7-15.4) 2.1 (1.4-6.1) 0.27

Complex perianal fistula, n (%)* 6 (37.5) 8 (61.5) 0.20

Median number of perianal procedures, n (IQR)

1 (0-2) 3 (1-5) 0.01

IFX duration, years (IQR) 3.6 (1.1-5.9) 1.2 (0.9-2.1) 0.06

Active smoking, n (%) 3 (18.8) 1 (7.7) 0.39

Concomitant antibiotics, n (%) 0 3 (23.1) 0.04

Concomitant IMM, n (%) 8 (50.0) 9 (69.2) 0.30

Median HBI (IQR) 2 (1-3) 4 (3-6) 0.02

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Median CRP, mg/L (IQR) 2.0 (1.0-3.0) 6.0 (1.5-11.5) 0.02 Median IFX level,µg/mL (IQR) 8.2 (7.3-9.1) 3.2 (0.8-5.3) <0.01

Presence of ATA, n (%) 2 (12.5) 7 (53.8) 0.02

*As per American Gastroenterological Association classification18

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Supplementary Figure 1. Receiver operator characteristic analysis for; (A) serum adalimumab levels and fistula healing; (B) serum adalimumab levels and fistula closure.

AUC, area under the curve; CI, confidence interval.

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Supplementary Figure 2.Receiver operator characteristic analysis for;(A)trough infliximab levels and fistula healing; (B) trough infliximab levels and fistula closure. AUC, area under the curve; CI, confidence interval.

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