英夫利昔单抗诱导治疗儿童克罗恩病疗效的预测指标分析

doi:10.12372/jcp.2025.24e0615

Abstract

Abstract:

Objective To explore the predictive indexes for the efficacy of infliximab induction therapy in children with Crohn's disease. Methods The clinical data of children diagnosed with Crohn's disease and initially treated with infliximab in the Gastroenterology Department from January 1, 2018 to July 31, 2023 were retrospectively analyzed. The clinical features and laboratory tests before treatment were compared between children with mucosal healing and those without mucosal healing after 14 weeks of infliximab induction therapy. Results Fifty-three children with Crohn's disease (39 boys and 14 girls) were included, and the median age of diagnosis was 12.0 (11.0-13.0) years. The median duration from disease onset to the first infliximab treatment was 5.0(2.0-12.0) months. All the 53 patients had moderate to severe Crohn's disease, including 27 cases with anal fistula, 9 cases with anal fistula combined with intestinal stenosis, 8 cases with intestinal stenosis, 7 cases with extensive intestinal lesions, and 2 cases with growth retardation. Multivariate logistic regression analysis showed that simple endoscopic score for Crohn's disease (SES-CD), C-reactive protein (CRP) and procalcitonin (PCT) might be related to the outcome of mucosal non-healing under endoscopy after infliximab induction therapy (P<0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of baseline SES-CD, CRP and PCT for predicting mucosal non-healing under endoscopy after infliximab induction therapy was 0.73, 0.77 and 0.77, respectively. The sensitivity, specificity and AUC of combined prediction of the three indicators were 0.96, 0.68 and 0.88, respectively. Conclusions The combination of SES-CD, CRP and PCT before infliximab treatment is more accurate in predicting the efficacy of infliximab induction therapy in children with Crohn's disease.

Key words: Crohn's disease, infliximab, prediction, mucosal healing, child

CLC Number:

YUE Yang, ZHANG Zhihua, LI Mei, LIU Zhifeng, GUO Hongmei. Predictors of efficacy of infliximab induction therapy in children with Crohn's disease[J].Journal of Clinical Pediatrics, 2025, 43(6): 426-431.

Figures/Tables 3

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Table 2

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References 26

[1]	van Rheenen PF, Aloi M, Assa A, et al. The medical management of paediatric Crohn's disease: an ECCO-ESPGHAN guideline update[J]. J Crohns Colitis, 2020, jjaa161.
[2]	Berg DR, Colombel JF, Ungaro R. The role of early biologic therapy in inflammatory bowel disease[J]. Inflamm Bowel Dis, 2019, 25(12): 1896-1905. doi: 10.1093/ibd/izz059 pmid: 30934053
[3]	中华医学会儿科学分会消化学组, 中华医学会儿科学分会临床营养学组. 儿童炎症性肠病诊断和治疗专家共识[J]. 中华儿科杂志, 2019, 57(7): 501-507.
	Subspecialty Group of Gastroenterology, the Society of Pediatrics, Chinese Medical Association; Subspecialty Group of Clinical Nutrition, the Society of Pediatrics, Chinese Medical Association. Chinese Medical Association. Expert consensus on the diagnosis and management of pediatric inflammatory bowel disease[J]. Zhonghua Erke Zazhi, 2019, 57(7): 501-507.
[4]	Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification[J]. Inflamm Bowel Dis, 2011, 17(6): 1314-1321. doi: 10.1002/ibd.21493 pmid: 21560194
[5]	Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn's disease activity index[J]. J Pediatr Gastroenterol Nutr, 1991, 12(4): 439-447.
[6]	Koutroumpakis E, Katsanos KH. Implementation of the simple endoscopic activity score in crohn's disease[J]. Saudi J Gastroenterol, 2016, 22(3): 183-191. doi: 10.4103/1319-3767.182455 pmid: 27184635
[7]	Turner D, Griffiths AM, Walters TD, et al. Appraisal of the pediatric Crohn's disease activity index on four prospectively collected datasets: recommended cutoff values and clinimetric properties[J]. Am J Gastroenterol, 2010, 105(9): 2085-2092. doi: 10.1038/ajg.2010.143 pmid: 20372111
[8]	Turner D, Ricciuto A, Lewis A, et al. STRIDE-Ⅱ: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the international organization for the study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD[J]. Gastroenterology, 2021, 160(5): 1570-1583. doi: 10.1053/j.gastro.2020.12.031 pmid: 33359090
[9]	Sakurai T, Saruta M. Positioning and usefulness of biomarkers in inflammatory bowel disease[J]. Digestion, 2023, 104(1): 30-41.
[10]	吴捷, 张添卓. 儿童炎症性肠病的研究现状及展望[J]. 临床儿科杂志, 2023, 41(11): 801-807.
	Wu J, Zhang TZ. An analysis of the present status and future prospects of pediatric inflammatory bowel disease[J]. Linchuang Erke Zazhi, 2023, 41(11): 801-807.
[11]	贾双珍, 孔琰, 刘前超, 等. 儿童炎症性肠病的精准治疗研究与应用[J]. 临床儿科杂志, 2025, 43(3): 226-232.
	Jia SZ, Kong Y, Liu QC, et al. Application of precision therapy in pediatric inflammatory bowel disease[J]. Linchuang Erke Zazhi, 2025, 43(3): 226-232.
[12]	Akutko K, Iwańczak B. Evaluation of fecal calprotectin, serum C-reactive protein, erythrocyte sedimentation rate, seromucoid and procalcitonin in the diagnostics and monitoring of Crohn's disease in children[J]. J Clin Med, 2022, 11(20): 6086.
[13]	Primas C, Reinisch W, Panetta JC, et al. Model informed precision dosing tool forecasts trough infliximab and associates with disease status and tumor necrosis factor-alpha levels of inflammatory bowel diseases[J]. J Clin Med, 2022, 11(12): 3316.
[14]	Sollelis E, Quinard RM, Bouguen G, et al. Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease[J]. World J Gastroenterol, 2019, 25(19): 2354-2364.
[15]	Tang J, Zhang CB, Lyu KS, et al. Association of polymorphisms in C1orf106, IL1RN, and IL10 with post-induction infliximab trough level in Crohn's disease patients[J]. Gastroenterol Rep (Oxf), 2019, 8(5): 367-373.
[16]	Constant BD, Khushal S, Jiang J, et al. Early inflammatory markers are associated with inadequate post-induction infliximab trough in pediatric Crohn's disease[J]. J Pediatr Gastroenterol Nutr, 2021, 72(3): 410-416.
[17]	Pesole PL, Liso M, Donghia R, et al. 90K/Mac-2 BP is a new predictive biomarker of response to infliximab therapy in IBD patients[J]. Int J Mol Sci, 2023, 24(4): 3955.
[18]	Buczyńska A, Grzybowska-Chlebowczyk U. Prognostic factors of biologic therapy in pediatric IBD[J]. Children (Basel), 2022, 9(10): 1558.
[19]	Atia O, Pujol-Muncunill G, Navas-López VM, et al. Children included in randomised controlled trials of biologics in inflammatory bowel diseases do not represent the real-world patient mix[J]. Aliment Pharmacol Ther, 2022, 56(5): 794-801.
[20]	Ma C, Battat R, Parker CE, et al. Update on C-reactive protein and fecal calprotectin: are they accurate measures of disease activity in Crohn's disease?[J]. Expert Rev Gastroenterol Hepatol, 2019, 13(4): 319-330.
[21]	Oussalah A, Laurent V, Bruot O, et al. Additional benefit of procalcitonin to C-reactive protein to assess disease activity and severity in Crohn's disease[J]. Aliment Pharmacol Ther, 2010, 32(9): 1135-1144.
[22]	Xu W, Hua Z, Wang Y, et al. The endoscopic prediction model of simple endoscopic score for Crohn's disease (SES-CD) as an effective predictor of intestinal obstruction in Crohn's disease: A multicenter long-term follow-up study[J]. Front Surg, 2022, 9: 984029.
[23]	Pavelock N, Masood U, Minchenberg S, et al. Effects of obesity on the course of inflammatory bowel disease[J]. Proc (Bayl Univ Med Cent), 2019, 32(1): 14-17. doi: 10.1080/08998280.2018.1542887 pmid: 30956572
[24]	Rowan CR, McManus J, Boland K, et al. Visceral adiposity and inflammatory bowel disease[J]. Int J Colorectal Dis, 2021, 36(11): 2305-2319. doi: 10.1007/s00384-021-03968-w pmid: 34104989
[25]	杨花花, 周旭春, 黄怡, 等. 克罗恩病英夫利昔单抗治疗失应答的影响因素分析[J]. 山东医药, 2022, 62(3): 30-34.
	Yang HH, Zhou XC, Huang Y, et al. Analysis of factors affecting loss of response to infliximab in the treatment of Crohn's disease[J]. Shandong Yiyao, 2022, 62(3): 30-34.
[26]	Ye XQ, Cai J, Yu Q, et al. Nomogram to predict primary non-response to infliximab in patients with Crohn's disease: a multicenter study[J]. Gastroenterol Rep (Oxf), 2020, 9(4): 329-338.

项目	黏膜愈合组(n=25)	黏膜未愈组(n=28)	统计量	P
男[n(%)]	18(72.0)	21(75.0)	χ²=0.06	0.805
病程[M(P₂₅~P₇₅)]/月	7.0(3.5~12.5)	4.5(1.3~9.8)	Z=1.73	0.084
诊断时年龄[M(P₂₅~P₇₅)]/岁	13.0(11.5~13.0)	12.0(11~13.8)	Z=0.00	1.000
疾病部位[n(%)]			－	0.584¹⁾
L1+L4	0(0)	2(7.1)
L2	3(12.0)	1(3.6)
L2+L4	3(12.0)	2(7.1)
L3	7(28.0)	10(35.7)
L3+L4	12(48.0)	12(42.9)
L4	0(0)	1(3.6)
疾病行为[n(%)]			χ²=0.00	0.983
B1(非狭窄非穿透)	16(64.0)	18(64.3)
B2(狭窄)	9(36.0)	10(35.7)
肛周瘘管[n(%)]	18(72.0)	18(64.3)	χ²=0.36	0.548
生长发育迟缓[n(%)]	1(4.0)	4(14.3)	－	0.355¹⁾
PCDAI($\bar{x}±s$)/分	30.3±13.7	37.5±12.0	t=2.04	0.047
BMI[M(P₂₅~P₇₅)]/kg·m^-2	16.2(14.6~18.4)	14.1(12.5~15.7)	Z=3.34	0.001
SES-CD($\bar{x}±s$)/分	16.2±8.4	24.6±9.6	t=3.36	0.001
钙卫蛋白[M(P₂₅~P₇₅)]/µg·g^-1	1 074.8(749.5~1 215.3)	1 074.8(901.8~1 298.4)	Z=0.61	0.544
CRP[M(P₂₅~P₇₅)]/mg·L^-1	14.0(0.0~29.9)	42.5(16.0~72.0)	Z=3.32	0.001
ESR[M(P₂₅~P₇₅)]/mm·h^-1	34.0(20.0~53.0)	41.0(23.5~56.0)	Z=0.13	0.894
Hb($\bar{x}±s$)/g·L^-1	107.4±20.1	104.1±17.9	t=0.64	0.525
血小板($\bar{x}±s$)×10⁹·L^-1	460.4±123.9	434.5±127.5	t=0.75	0.458
PCT[M(P₂₅~P₇₅)]/ng·mL^-1	0.05(0.04~0.08)	0.09(0.06~0.11)	Z=3.41	0.001
白蛋白($\bar{x}±s$)/g·L^-1	35.8±4.7	34.2±6.4	t=1.08	0.286
球蛋白($\bar{x}±s$)/g·L^-1	33.9±4.7	34.5±5.4	t=0.44	0.662
总胆红($\bar{x}±s$)/µmol·L^-1	5.3±2.4	5.5±2.0	t=0.29	0.773
N/L[M(P₂₅~P₇₅)]	2.4(1.9~3.8)	3.2(1.9~3.9)	Z=1.02	0.310
N/A[M(P₂₅~P₇₅)]	0.2(0.1~0.3)	0.2(0.1~0.3)	Z=0.43	0.669
N/B[M(P₂₅~P₇₅)]	1.6(0.7~2.2)	1.4(0.8~1.9)	Z=0.46	0.643
药物剂量($\bar{x}±s$)/mg·kg^-1	6.4±1.7	7.0±1.2	t=1.50	0.140

因素	偏回归系数	标准误	χ²值	P	OR(95%CI)
PCDAI	0.10	0.05	3.63	0.057	1.11(1.00~1.22)
SES-CD	0.11	0.05	3.95	0.047	1.11(1.00~1.24)
CRP	0.06	0.03	5.37	0.021	1.06(1.01~1.12)
PCT	0.03	0.01	4.97	0.026	1.03(1.00~1.06)
BMI	－0.36	0.19	3.66	0.056	0.70(0.49~1.01)
常量	3.00	3.38	0.79	0.376	－

Predictors of efficacy of infliximab induction therapy in children with Crohn's disease

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