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Impact of Tumor Necrosis Factor Antagonist Therapy on Circulating Angiopoietin-like Protein 8 (ANGPTL8) Levels in Crohn’s Disease—A Prospective Multi-Center Study

  • Mohammad Shehab
  • , Sharifa Al-Fajri
  • , Ahmed Alanqar
  • , Mohammad Alborom
  • , Fatema Alrashed
  • , Fatemah Alshammaa
  • , Ahmad Alfadhli
  • , Sriraman Devarajan
  • , Irina Alkhairi
  • , Preethi Cherian
  • , Jehad Abubaker
  • , Mohamed Abu-Farha
  • , Fahd Al-Mulla

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Crohn’s disease (CD) is a chronic disease perpetuated through key pro-inflammatory molecules, including tumor necrosis factor-alpha (TNFα). Angiopoietin-like protein 8 (ANGPTL8) may contribute to inflammation cascades. This study aimed to investigate how ANGPTL8 levels are influenced in patients with CD prior to and following anti-TNF therapy. Methods: Patients were divided into 3 groups. Patients with CD in clinical remission receiving IFX for at least 24 weeks (IFX-experienced group), patients scheduled to start IFX (IFX-naïve group), and healthy controls (control group). In the IFX-experienced group, ANGPTL8 levels were measured 24 h before the next maintenance IFX dose. In the IFX-naïve group, levels were measured at week 0 and week 24, and in the control group, they were measured randomly. Results: The total number of participants was 166. The numbers of IFX-experienced, IFX-naïve patients, and healthy controls were 82, 13, and 71, respectively. Mean age ranged from 27 to 33 years of age across the three groups. Eighty-four (51%) participants were female. ANGPTL8 levels were significantly higher in patients with CD (138.26 ± 8.47 pmol) compared to the healthy control group (102.52 ± 5.99 pmol, p = 0.001). Among IFX-naïve patients receiving anti-TNFα treatment, ANGPTL8 levels decreased significantly from 145.06 ± 17.93 pmol pre-treatment (week 0) to 81.78 ± 10.61 pmol post-treatment (week 24), p = 0.007. Conclusions: Our findings suggest that ANGPTL8 levels are elevated in CD and may be involved in the inflammatory process. The marked reduction in ANGPTL8 levels following anti-TNFα treatment indicates its potential as a biomarker for treatment response. Further research should focus on the exact mechanisms through which ANGPTL8 influences CD progression and its utility in clinical practice.

Original languageEnglish
Article number5006
JournalJournal of Clinical Medicine
Volume14
Issue number14
DOIs
StatePublished - Jul 2025

Keywords

  • ANGPTL8
  • CD
  • infliximab

Funding Agency

  • Kuwait Foundation for the Advancement of Sciences

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