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©The Author(s) 2022.
World J Gastroenterol. Jun 21, 2022; 28(23): 2582-2596
Published online Jun 21, 2022. doi: 10.3748/wjg.v28.i23.2582
Published online Jun 21, 2022. doi: 10.3748/wjg.v28.i23.2582
Table 1 Clinical characteristics of Crohn‘s disease patients with endoscopic remission
| Variable | Week 14 (after initial IFX therapy) | Week 54 (after initial IFX therapy) n = 54 | ||||
| Total, n = 93 | ER at week 54, n = 67 | EA at week 54, n = 26 | Total, n = 54 | ER at week 108, n = 42 | EA at week 108, n = 12 | |
| Median age in yr, mean ± SD | 28.96 ± 9.37 | 29.03 ± 10.09 | 28.77 ± 7.39 | 27.57 ± 10.13 | 26.93 ± 9.87 | 29.83 ± 11.13 |
| Course in yr, median (IQR) | 3.0 (1.0, 6.0) | 2.0 (1.0, 6.0) | 3.5 (2.0, 8.3) | 2.0 (1.0, 5.0) | 2.0 (1.0, 5.0) | 2.0 (1.3, 8.5) |
| Male sex, n (%) | 55 (59.1) | 43 (64.2) | 12 (46.2) | 35 (64.8) | 28 (66.7) | 7 (58.3) |
| Disease location, n (%) | ||||||
| L1 (terminal ileum) | 18 (19.4) | 14 (20.9) | 4 (15.4) | 10 (18.5) | 9 (21.4) | 1 (8.3) |
| L2 (colon) | 11 (11.8) | 6 (9.0) | 5 (19.2) | 5 (9.3) | 4 (9.5) | 1 (8.3) |
| L3 (ileocolon) | 64 (68.8) | 47 (70.1) | 17 (65.4) | 39 (72.2) | 29 (69.0) | 10 (83.3) |
| L4 (upper digestive tract) | 22 (23.7) | 15 (22.4) | 7 (26.9) | 14 (25.9) | 11(26.2) | 3 (25.0) |
| Disease behavior, n (%) | ||||||
| B1 (no) | 19 (20.4) | 15 (22.4) | 4 (15.4) | 13 (24.1) | 9 (21.4) | 4 (33.3) |
| B2 (stenosis) | 11 (11.8) | 9 (13.4) | 2 (7.7) | 6 (11.1) | 5 (11.9) | 1 (8.3) |
| B3 (penetration) | 40 (43.0) | 27 (40.3) | 13 (50.0) | 23 (42.6) | 18 (42.9) | 5 (41.7) |
| B2 (stenosis) + B3 (penetration) | 23 (24.7) | 16 (23.9) | 7 (26.9) | 12 (22.2) | 10 (23.8) | 2 (16.7) |
| Perianal diseases, n (%) | 55 (59.1) | 38 (56.7) | 17 (65.4) | 32 (59.3) | 25 (59.5) | 7 (58.3) |
| Previous medical therapy, n (%) | 64 (68.8) | 46 (68.7) | 18 (69.2) | 34 (63.0) | 25 (59.5) | 9 (75.0) |
| Previous surgical therapy, n (%) | 15 (16.1) | 11 (16.4) | 4 (15.4) | 8 (14.8) | 8 (19.0) | 0 (0.0) |
| Laboratory indicators, mean ± SD | ||||||
| Fecal calprotectin, μg/g | 399.96 ± 562.47 | 178.62 ± 242.38 | 970.35 ± 734.49 | 353.17 ± 557.71 | 178.57 ± 276.56 | 964.25 ± 830.56 |
| IFX trough level, μg/ml | 6.12 ± 3.72 | 7.23 ± 3.48 | 3.25 ± 2.67 | 3.80 ± 2.25 | 4.37 ± 2.02 | 1.80 ± 1.90 |
| White blood count, × 109/L | 5.32 ± 1.87 | 5.16 ± 1.47 | 5.73 ± 2.65 | 5.27 ± 1.41 | 5.27 ± 1.43 | 5.28 ± 1.41 |
| Hematoglobin, g/L | 128.37 ± 20.42 | 130.96 ± 20.03 | 121.69 ± 20.27 | 136.59 ± 16.06 | 136.79 ± 16.94 | 135.92 ± 13.13 |
| Platelet, × 109/L | 210.66 ± 69.77 | 202.36 ± 58.34 | 232.04 ± 90.94 | 205.02 ± 46.19 | 204.62 ± 45.82 | 206.42 ± 49.54 |
| Erythrocyte sedimentation rate, mm/h | 9.88 ± 12.25 | 6.89 ± 7.96 | 17.46 ± 17.28 | 7.31 ± 10.35 | 6.33 ± 6.89 | 10.75 ± 17.97 |
| Albumin, g/L | 42.13 ± 4.17 | 42.65 ± 3.93 | 40.77 ± 4.54 | 44.51 ± 3.40 | 44.99 ± 3.38 | 42.85 ± 3.02 |
| C-reactive protein, mg/dl | 2.98 ± 5.43 | 1.82 ± 2.77 | 5.96 ± 8.69 | 1.99 ± 3.18 | 1.23 ± 1.79 | 4.66 ± 5.19 |
Table 2 Predictive indicators of endoscopic relapse in Crohn's disease patients with endoscopic remission
| Variable | Week 14 (after initial IFX therapy), n = 93 | Week 14 (after initial IFX therapy), n = 54 | ||||||
| Predict endoscopic relapse at week 54 | Predict endoscopic relapse at week 108 | |||||||
| Univariate analysis | Multivariable analysis | Univariate analysis | Multivariable analysis | |||||
| OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value | |
| Median age in year, median (IQR) | 0.997 (0.950-1.047) | 0.904 | — | — | 1.028 (0.967-1.093) | 0.381 | — | — |
| Course in year, median (IQR) | 1.054 (0.945-1.176) | 0.346 | — | — | 1.065 (0.906-1.253) | 0.444 | — | — |
| Male sex, n (%) | 0.478 (0.191-1.199) | 0.116 | — | — | 0.700 (0.188-2.607) | 0.595 | — | — |
| Disease location, n (%) | ||||||||
| L1 (terminal ileum) | 0.413 (0.114-1.495) | 0.178 | — | — | 1.158 0.117-11.454) | 0.900 | — | — |
| L2 (colon) | 1.453 (0.430-4.908) | 0.548 | — | — | 3.000 (0.341-26.427) | 0.322 | — | — |
| L3 (ileocolon) | — | — | — | — | — | — | — | — |
| L4 (upper digestive tract) | 1.277 (0.452-3.612) | 0.645 | — | — | 0.939 (0.215-4.113) | 0.934 | — | — |
| Disease behavior, n (%) | ||||||||
| B1 (no) | — | — | — | — | — | — | — | — |
| B2 (stenosis) | 0.889 (0.345-2.294) | 0.808 | — | — | 0.600 (0.141-2.561) | 0.490 | — | — |
| B3 (penetration) | 1.860 (0.658-5.264) | 0.242 | — | — | 0.700 (0.188-2.607) | 0.595 | — | — |
| B2 (stenosis) + B3 (penetration) | — | — | — | — | — | — | — | — |
| Perianal diseases, n (%) | 1.442 (0.562-3.696) | 0.446 | — | — | 0.952 (0.259-3.502) | 0.941 | — | — |
| Previous medical therapy, n (%) | 1.027 (0.386-2.736) | 0.957 | 2.040 (0.481-8.650) | 0.333 | ||||
| Previous surgical therapy, n (%) | 0.926 (0.266-3.218) | 0.903 | — | — | — | — | — | — |
| Laboratory indicators, median (IQR) | ||||||||
| Fecal calprotectin, μg/g | 1.003 (1.002-1.005) | 0.000 | 1.002 (1.001-1.004) | 0.002 | 1.002 (1.001-1.004) | 0.001 | NS | NS |
| IFX trough level, μg/mL | 0.650 (0.532-0.796) | 0.000 | 0.666 (0.514-0.862) | 0.002 | 0.470 (0.289-0.766) | 0.002 | 0.466 (0.247-0.877) | 0.018 |
| White blood count, x 109/L | 1.167 (0.921-1.478) | 0.201 | — | — | 1.004 (0.636-1.586) | 0.986 | — | — |
| Hematoglobin, g/L | 0.977 (0.954-1.000) | 0.053 | — | — | 0.997 (0.957-1.038) | 0.867 | — | — |
| Platelet, x 109/L | 1.006 (0.999-1.013) | 0.081 | — | — | 1.001 (0.987-1.015) | 0.904 | — | — |
| Erythrocyte sedimentation rate, mm/h | 1.073 (1.028-1.120) | 0.001 | NS | NS | 1.035 (0.978-1.096) | 0.239 | — | — |
| Albumin, g/L | 0.895 (0.800-1.002) | 0.054 | — | — | 0.821 (0.667-1.010) | 0.062 | — | — |
| C-reactive protein, mg/dL | 1.245 (1.080-1.435) | 0.003 | NS | NS | 1.389 (1.070-1.804) | 0.014 | 1.590 (1.007-2.510) | 0.047 |
Table 3 Predictive value of indicators on endoscopic relapse
| Youden index | Sensitivity | Specificity | Positive predictive value | Negative predictive value | Area under the ROC curve | P value | |
| Predictors at week 14 of Endoscopic relapse at week 54 | |||||||
| ITL ≤ 5.6 μg/mL | 0.61 (0.41-0.72) | 0.92 (0.75-0.99) | 0.69 (0.56-0.79) | 0.53 (0.44-0.62) | 0.96 (0.86-0.99) | 0.83 (0.73-0.90) | < 0.001 |
| FCP > 238 μg/g | 0.64 (0.38-0.78) | 0.73 (0.52-0.88) | 0.91 (0.82-0.97) | 0.76 (0.59-0.88) | 0.90 (0.82-0.94) | 0.82 (0.72-0.89) | < 0.001 |
| ITL ≤ 5.6 μg/mL and FCP > 238 μg/g | 0.63 (0.40-0.80) | 0.69 (0.48-0.86) | 0.94 (0.85-0.98) | 0.82 (0.63-0.92) | 0.89 (0.82-0.93) | 0.82 (0.72-0.89) | < 0.001 |
| ITL ≤ 5.6 μg/mL or FCP > 238 μg/g | 0.62 (0.47-0.74) | 0.96 (0.80-1.00) | 0.66 (0.53-0.77) | 0.52 (0.44-0.60) | 0.98 (0.87-1.00) | 0.81 (0.71-0.88) | < 0.001 |
| Predictors at week 54 of Endoscopic relapse at week 108 | |||||||
| ITL ≤ 2.1 μg/mL | 0.68 (0.40-0.87) | 0.75 (0.43-0.95) | 0.93 (0.81-0.99) | 0.75 (0.49-0.90) | 0.93 (0.83-0.97) | 0.85 (0.72-0.93) | < 0.001 |
| CRP > 3.0 mg/dL | 0.45 (0.20-0.68) | 0.50 (0.21-0.79) | 0.95 (0.84-0.99) | 0.75 (0.41-0.93) | 0.87 (0.79-0.92) | 0.73 (0.60-0.84) | 0.012 |
| ITL ≤ 2.1 μg/mL and CRP > 3.0 mg/dL | 0.33 (0.08-0.58) | 0.33 (0.10-0.65) | 1.00 (0.92-1.00) | 1.00 (1.00-1.00) | 0.84 (0.78-0.89) | 0.67 (0.53-0.79) | 0.019 |
| ITL ≤ 2.1 μg/mL or CRP > 3.0 mg/dL | 0.80 (0.50-0.93) | 0.92 (0.62-1.00) | 0.88 (0.74-0.96) | 0.69 (0.49-0.84) | 0.97 (0.85-1.00) | 0.90 (0.79-0.96) | ＜0.001 |
Table 4 Previous research of infliximab trough level on deep remission in inflammatory bowel disease
| Study design | Optimal cut-off value | Predictive content | Yes/No, n | SE | SP | PPV | NPV | AUC |
| A retrospective observational single-center study in China | 4.85 μg/mL at week 14 | Mucosal healing (complete absence of any sign of ulceration) | 82/59 | 67% | 80% | 0.80 | ||
| 4.85 μg/mL at week 14 | Mucosal healing (CDEIS of < 3) | 84/57 | 68% | 83% | 0.79 | |||
| 2.85 μg/mL at week 30 | Mucosal healing (complete absence of any sign of ulceration) | 59/50 | 73% | 84% | 0.78 | |||
| 2.85 μg/mL at week 30 | Mucosal healing (CDEIS of < 3) | 62/47 | 68% | 81% | 0.73 | |||
| A retrospective observational single-center study in China | 2.50 μg/mL at week 14 | Mucosal healing (SES-CD/Rutgeerts of 0 or 1) at week 52 | 31/42 | 87% | 60% | 0.70 | ||
| 2.50 μg/mL at week 14 | Sustained remission (no treatment failure, no need for surgery or intensification of IFX nor new introduction during IFX therapy) at week 52 | 70/38 | 64% | 63% | 0.70 | |||
| A prospective multicenter study in Spanish | 3.40 μg/mL | (1) SES-CD<3 for CD patients; (2) Rutgeerts score < i2 for CD patients in the postoperative setting; and (3) Mayo endoscopic score < 2 for UC patients | 58/30 | 60% | 60% | 73% | 42% | 0.63 |
| A multicenter, randomized, double-blind, controlled trial in Europe | 23.10 mg/L at week 2 | Endoscopic remission (CDEIS < 3) at week 12 | 54/52 | 56% | 80% | 72% | 65% | 0.67 |
| 10.00 mg/L at week 6 | Endoscopic remission (CDEIS < 3) at week 12 | 54/52 | 37% | 89% | 76% | 59% | 0.64 | |
| 10.60 mg/L (dose escalation to 10 mg/kg) | The absence of ulcers at week 54 | 85/51 | 94% | 42% | 49% | 92% | 0.71 | |
| A retrospective multicenter study in United States | 9.70 μg/mL | Endoscopic remission (absence of any mucosal break (ulceration or erosion)/Rutgeerts score of ≤ i1) | 62/34 | 57% | 73% | 80% | 48% | 0.65 |
| 9.80 μg/mL | Histologic remissions (absence of active inflammation) | 43/44 | 63% | 66% | 64% | 64% | 0.62 | |
| 2.20 μg/mL | Biochemical remission (CRP ≤ 5 mg/dL) | 48/23 | 92% | 35% | 75% | 67% | 0.64 | |
| A retrospective observational single-center study in Japan | 4.00 μg/mL | Mucosal healing (modified Rutgeerts scoring system: 0 or 1) after 30 days | 20/58 | 71% | 70% | 0.63 | ||
| 0.60 μg/mL | CRP normalization (≤ 0.3 mg/dL) | 28/22 | 73% | 62% | 0.67 | |||
| 1.00 μg/mL | Serum albumin normalization (≥ 4.0 mg/dL) | 17/33 | 67% | 71% | 0.72 | |||
| 1.10 μg/mL | Fecal calprotectin (≥ 300 μg/g) | 13/25 | 72% | 56% | 0.63 | |||
| A retrospective cross-sectional multicenter study in South Korea | 4.20 μg/mL | Mucosal healing (SES-CD = 0) | 51/54 | 65% | 70% | 67% | 68% | 0.68 |
| 3.71 μg/mL | Partial mucosal healing (SES-CD < 3) | 63/42 | 70% | 71% | 79% | 61% | 0.73 | |
| 3.26 μg/mL | Clinical remission (PCDAI < 10) | 95/10 | 71% | 100% | 100% | 73% | 0.90 | |
| 2.52 μg/mL | Biochemical remission (CRP < 0.3 mg/dL) | 87/18 | 86% | 56% | 90% | 46% | 0.71 | |
| A prospective cohort multicenter study in Canada | 8.02 μg/mL | Histologic remission (an absence of active chronic inflammation) | 56/48 | 79% | 68% | 0.72 | ||
| 8.27 μg/mL | Sustained histologic remission (histologic remission documented at both the baseline and follow-up colonoscopies) | 36/16 | 88% | 72% | 0.77 | |||
| A retrospective cross-sectional study in United Kingdom | 7.10 μg/mL | Fistula healing (no spontaneous discharge or no discharge on palpation in the absence of seton drainage) | 18/11 | 78% | 100% | 0.93 | ||
| 7.10 μg/mL | Fistula closure (the absence of an external skin opening) | 13/16 | 64% | 100% | 0.97 |
- Citation: Cao WT, Huang R, Liu S, Fan YH, Xu MS, Xu Y, Ni H. Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn’s disease under infliximab therapy. World J Gastroenterol 2022; 28(23): 2582-2596
- URL: https://www.wjgnet.com/1007-9327/full/v28/i23/2582.htm
- DOI: https://dx.doi.org/10.3748/wjg.v28.i23.2582