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

## TL;DR

This study shows that ANGPTL8 levels are higher in Crohn’s disease patients and drop after anti-TNF therapy, suggesting it could be a useful biomarker for treatment response.

## Contribution

The study is the first to show that ANGPTL8 levels decrease significantly after anti-TNF therapy in Crohn’s disease patients.

## Key findings

- ANGPTL8 levels were significantly higher in Crohn’s disease patients compared to healthy controls.
- Anti-TNF therapy led to a significant reduction in ANGPTL8 levels in treatment-naïve Crohn’s disease patients.
- ANGPTL8 may serve as a potential biomarker for inflammation and treatment response in Crohn’s disease.

## 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.