دورية أكاديمية
Serum Immune Profiling in Paediatric Crohn's Disease Demonstrates Stronger Immune Modulation With First-Line Infliximab Than Conventional Therapy and Pre-Treatment Profiles Predict Clinical Response to Both Treatments.
| العنوان: | Serum Immune Profiling in Paediatric Crohn's Disease Demonstrates Stronger Immune Modulation With First-Line Infliximab Than Conventional Therapy and Pre-Treatment Profiles Predict Clinical Response to Both Treatments. |
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| المؤلفون: | Jongsma MME; Department of Pediatric Gastroenterology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., Costes LMM; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., Tindemans I; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., Cozijnsen MA; Department of Pediatric Gastroenterology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., Raatgreep RHC; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., van Pieterson M; Department of Pediatric Gastroenterology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., Li Y; Department of Pathology & Clinical Bioinformatics, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Escher JC; Department of Pediatric Gastroenterology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., de Ridder L; Department of Pediatric Gastroenterology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands., Samsom JN; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands. |
| المصدر: | Journal of Crohn's & colitis [J Crohns Colitis] 2023 Aug 21; Vol. 17 (8), pp. 1262-1277. |
| نوع المنشور: | Randomized Controlled Trial; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 101318676 Publication Model: Print Cited Medium: Internet ISSN: 1876-4479 (Electronic) Linking ISSN: 18739946 NLM ISO Abbreviation: J Crohns Colitis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : Oxford : Oxford University Press Original Publication: Amsterdam : Elsevier Science |
| مواضيع طبية MeSH: | Crohn Disease*/metabolism, Child ; Humans ; Infliximab/therapeutic use ; Azathioprine/therapeutic use ; C-Reactive Protein ; Remission Induction ; Treatment Outcome ; Gastrointestinal Agents/therapeutic use |
| مستخلص: | Background: Despite its efficacy, rational guidance for starting/stopping first-line biologic treatment in individual paediatric Crohn's disease [CD] patients is needed. We assessed how serum immune profiles before and after first-line infliximab [FL-IFX] or conventional [CONV] induction therapy associate with disease remission at week 52. Methods: Pre- [n = 86], and 10-14-week post-treatment [n = 84] sera were collected from patients with moderate-to-severe paediatric CD in the TISKids trial, randomized to FL-IFX [n = 48; five 5-mg/kg infusions over 22 weeks] or CONV [n = 43; exclusive enteral nutrition or oral prednisolone]; both groups received azathioprine maintenance. The relative concentrations of 92 inflammatory proteins were determined with Olink Proteomics; fold changes [FC] with |log2FC| > 0.5 after false discovery rate adjustment were considered significant. Results: FL-IFX modulated a larger number of inflammatory proteins and induced stronger suppression than CONV; 18/30 proteins modulated by FL-IFX were not regulated by CONV. Hierarchical clustering based on IFX-modulated proteins at baseline revealed two clusters of patients: CD-hi patients had significantly higher concentrations of 23/30 IFX-modulated proteins [including oncostatin-M, TNFSF14, HGF and TGF-α], and higher clinical disease activity, C-reactive protein and blood neutrophils at baseline than CD-lo patients. Only 24% of CD-hi FL-IFX-treated patients maintained remission without escalation at week 52 vs 58% of CD-lo FL-IFX-treated patients. Similarly, 6% of CD-hi CONV-treated patients achieved remission vs 20% of CONV-treated CD-lo patients. Clustering based on immune profiles post-induction therapy did not relate to remission at week 52. Conclusion: FL-IFX leads to stronger reductions and modulates more immune proteins than CONV. Stratification on pre-treatment profiles of IFX-modulated proteins directly relates to maintenance of remission without treatment escalation. Trial Registration Number: NCT02517684. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.) |
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| معلومات مُعتمدة: | Netherlands ZONMW_ ZonMw |
| فهرسة مساهمة: | Keywords: Proteomics; anti-TNF; inflammatory bowel disease |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02517684 |
| المشرفين على المادة: | B72HH48FLU (Infliximab) MRK240IY2L (Azathioprine) 9007-41-4 (C-Reactive Protein) 0 (Gastrointestinal Agents) |
| SCR Disease Name: | Pediatric Crohn's disease |
| تواريخ الأحداث: | Date Created: 20230319 Date Completed: 20230822 Latest Revision: 20230823 |
| رمز التحديث: | 20230823 |
| مُعرف محوري في PubMed: | PMC10441564 |
| DOI: | 10.1093/ecco-jcc/jjad049 |
| PMID: | 36934327 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1876-4479 |
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| DOI: | 10.1093/ecco-jcc/jjad049 |