The Efficacy and Safety of Infliximab Combination With Azathioprine in Crohn's Disease in Children

Study on the Efficacy and Safety of Infliximab Monotherapy or in Combination With Azathioprine in the Treatment of Crohn's Disease in Children

The goal of this clinical trial is to investigate whether there are significant differences in the efficacy of infliximab monotherapy and combined azathioprine therapy in treating pediatric Crohn's disease, as well as whether there are differences in the safety of these two treatment regimens during long-term use. The main questions it aims to answer are:

Is infliximab combined with azathioprine superior to monotherapy in inducing and maintaining remission of Crohn's disease in children? In long-term treatment, can infliximab combined with azathioprine more effectively reduce disease activity and the occurrence of complications, but the incidence of adverse reactions is not higher than that of monotherapy? Researchers will compare the treatment of infliximab combined with azioprine with that of infliximab monotherapy to assess the efficacy and safety of both in inducing and maintaining remission of Crohn's disease in children.

Participants will:

Take drug ABC or a placebo every day for 4 months Experimental group: Infliximab, administered intravenously at 5mg/kg every 8 weeks at weeks 0, 2, 6 and thereafter, along with azathioprine, taken orally at 1.5-2.5mg/kg daily.

Control group: Infliximab (Remicade), administered intravenously at 5mg/kg every 8 weeks at weeks 0, 2, 6 and thereafter.

A comprehensive disease assessment will be conducted at the hospital in the 14th and 54th weeks.

Record their symptoms, signs and test results.

Study Overview

• Status: Not yet recruiting
• Conditions: Crohn's Diseases; Crohn's Disease in Pediatric Patient
• Intervention / Treatment: Drug: Infliximab combined with azathioprine therapy; Drug: Infliximab monotherapy

Detailed Description

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD). In recent years, the incidence of CD in children has shown a significant upward trend globally, and it has also increased significantly in Chinese children. According to epidemiological studies, the incidence of CD in Chinese children is approximately 2.5 to 11 cases per 100,000 people per year. CD in children is usually more severe and can significantly affect the psychological and social functions as well as physical development of patients. Infliximab (IFX), as the first tumor necrosis factor-α (TNF-α) antagonist approved for the treatment of CD, specifically binds and neutralizes TNF-α, inhibiting intestinal inflammatory responses and promoting mucosal healing. In the field of pediatric CD, several studies have preliminarily confirmed that IFX monotherapy can effectively induce clinical remission, promote growth and development, and reduce hormone dependence. However, a considerable proportion (37.8% to 43.3%) of CD patients treated with anti-TNF-α therapy will develop secondary adaptive responses (LOR). Therefore, they need dose intensification, switching to other anti-TNF drugs, or switching to drugs with different mechanisms of action for intervention. Multiple studies have shown that the combination of anti-TNF-α drugs with immunomodulators may reduce the production of anti-drug antibodies and improve efficacy, thereby maintaining remission. The most commonly used immunomodulators for IBD are thiopurine drugs, such as azathioprine or 6-mercaptopurine. Some previous studies suggest that combination therapy may be superior to monotherapy in adult CD, but its efficacy and safety for this special group of children remain controversial: on the one hand, the immune system of children is not yet fully developed, and combined therapy may further increase the risks of infection and bone marrow suppression; on the other hand, children have urgent needs for growth and development, and the effectiveness and safety of combined therapy in improving growth retardation and promoting mucosal healing still require more high-quality evidence to support. Currently, there are limited clinical studies on the use of IFX monotherapy or IFX combined with azathioprine for pediatric CD in both domestic and international settings, and most of them are small-sample retrospective studies, lacking large-sample prospective randomized controlled trial (RCT) data. At the same time, there is also a lack of evidence on the optimal timing of combined therapy, dose adjustment strategies, and long-term follow-up safety (such as long-term tumor risk, fertility impact, etc.) for combined therapy, which cannot provide sufficient evidence for clinical decision-making. Based on the above background, this study aims to compare the efficacy and safety of IFX monotherapy and IFX combined with azathioprine in treating pediatric CD, in order to clarify the differences in efficacy of the two treatment regimens in inducing remission, maintaining remission, mucosal healing, and growth and development of pediatric CD, and to comprehensively analyze their short-term and long-term safety characteristics, in order to provide more reliable evidence-based medical evidence for individualized treatment of pediatric CD, optimize clinical treatment pathways, and ultimately improve the long-term prognosis and quality of life of children.

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Youyou Luo; Phone Number: 13867467021; Email: looloohi@zju.edu.cn

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • The First People's Hospital of Yunnan
      • Contact: Yunfen Tian; Phone Number: 13769112828; Email: 136506595@qq.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The Children's Hospital of Zhejiang University School of Medicine
      • Contact: Youyou Luo; Phone Number: 13867467021; Email: looloohi@zju.edu.cn
    • Jinhua, Zhejiang, China, 321000
      • JinHua Maternal & Child Health Care Hospital
      • Contact: Paijian Lai; Phone Number: 13665883260; Email: 13665883260@163.com
    • Wenzhou, Zhejiang, China, 325000
      • Second Affiliated Hospital of Wenzhou Medical University
      • Contact: Shuzi Zheng; Phone Number: 18857704481; Email: 15869126891@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnose Crohn's disease based on the 2019 Expert Consensus for the Diagnosis and Treatment of Pediatric Inflammatory Bowel Disease.
• The baseline Pediatric Crohn's Disease Activity Index (PCDAI) value is ≥ 30.
• None of the patients had received treatment with azathioprine, 6-mercaptopurine, or anti-TNF biological agents before.
• Patients who received the following adjunctive treatments also meet the participation criteria: acid-suppressing drugs (if the dose was stable for at least 2 weeks before enrollment, it is applicable), enteral nutrition (with a stable plan for 2 weeks). Rectal, intravenous, or oral corticosteroids are not allowed, and they must be discontinued at least 2 weeks before enrollment.

Exclusion Criteria:

• Suffering from short bowel syndrome, ostomy surgery, symptomatic stenosis, abscess, or a recent history of abdominal surgery (within 6 months)
• History of tuberculosis or other granulomatous infections, positive chest imaging or positive tuberculin skin test
• Recent opportunistic infection history (within 6 months), active hepatitis B or C infection, human immunodeficiency virus infection
• Multiple sclerosis, cancer
• Homozygous mutations in NUDT15 or TPMT genes, or heterozygous mutations in at least one of the above genes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination therapy; Infliximab is administered intravenously at 5mg/kg every 8 weeks at weeks 0, 2, 6 and thereafter. Simultaneously, azathioprine is taken orally at 1.5 - 2.5mg/kg daily.	Drug: Infliximab combined with azathioprine therapy; Infliximab is administered intravenously at 5mg/kg every 8 weeks at weeks 0, 2, 6 and thereafter. Simultaneously, azathioprine is taken orally at 1.5 - 2.5mg/kg daily.
Active Comparator: Monotherapy; Infliximab is administered intravenously at 5mg/kg every 8 weeks at weeks 0, 2, 6 and thereafter.	Drug: Infliximab monotherapy; Infliximab is administered intravenously at 5mg/kg every 8 weeks at weeks 0, 2, 6 and thereafter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The clinical remission rates（(Pediatric Crohn's Disease Activity Index）in the 14th week and the 54th week	The clinical remission rateS of the children was evaluated using the PCDAI (Pediatric Crohn's Disease Activity Index). PCDAI<10 was considered as clinical remission.	the 14th week and the 54th week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of adverse reactions between the two treatment regimens within 54 weeks	Adverse reactions include infections, tumors, liver and kidney function impairments, myocardial damage, and bone marrow transplantation, etc Compare the incidence rates of adverse reactions between the two groups。	within 54 weeks
The mucosal healing rates （Simple Endoscopic Score for Crohn's Disease）in the 14th week and the 54th week	The SES-CD（Simple Endoscopic Score for Crohn's Disease）obtained under colonoscopy was used to evaluate the condition of mucosal healing. SES-CD<3 was defined as mucosal healing.	the 14th week and the 54th week
Patient-reported outcomes（PRO2） for the 14th week and the 54th week	The patient-reported outcomes for Crohn's disease use standardized assessment tools, namely the PRO2 scale, which includes two core symptoms: "abdominal pain" and "frequency of defecation". The minimum and maximum values of the PRO2 scale are 0 and above 30 respectively. Higher scores mean a worse outcome.	the 14th week and the 54th week

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine
• Collaborators: Second Affiliated Hospital of Wenzhou Medical University; The First People's Hospital of Yunnan

Publications and helpful links

General Publications

• Kappelman MD, Wohl DA, Herfarth HH, Firestine AM, Adler J, Ammoury RF, Aronow JE, Bass DM, Bass JA, Benkov K, Tobi CB, Boccieri ME, Boyle BM, Brinkman WB, Cabera JM, Chun K, Colletti RB, Dodds CM, Dorsey JM, Ebach DR, Entrena E, Forrest CB, Galanko JA, Grunow JE, Gulati AS, Ivanova A, Jester TW, Kaplan JL, Kugathasan S, Kusek ME, Leibowitz IH, Linville TM, Lipstein EA, Margolis PA, Minar P, Molle-Rios Z, Moses J, Olano KK, Osaba L, Palomo PJ, Pappa H, Park KT, Pashankar DS, Pitch L, Robinson M, Samson CM, Sandberg KC, Schuchard JR, Seid M, Shelly KA, Steiner SJ, Strople JA, Sullivan JS, Tung J, Wali P, Zikry M, Weinberger M, Saeed SA, Bousvaros A. Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial. Gastroenterology. 2023 Jul;165(1):149-161.e7. doi: 10.1053/j.gastro.2023.03.224. Epub 2023 Mar 31.

Helpful Links

• Website links of the references

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: February 7, 2026
• First Submitted That Met QC Criteria: February 15, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 15, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: CHZJU2025IIT017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No