P0528 Leukocyte Adhesive Function as Potential Predictive Marker for Treatment Response to Vedolizumab Among Bio-naive Patients with Crohn’s Disease
Authors: Liu J , Cheng Q , Cao Q 
Published: January 2025

Abstract

Background
Vedolizumab (VDZ) is approved for the treatment of Crohn’s diseases (CD), but around 60% of patients fail to respond. Predicting response to VDZ, especially prior to treatment, is desirable but remains challenging. In this study, we investigated if α4β7 and α4β1 integrin activity may be used to predict response to VDZ.

Methods
Both α4β7 and α4β1 integrin activity were assessed using Leukocyte adhesive function assay (LAFA). LAFA uses microfluidic techniques to mimic blood circulation in vitro. Blood samples were fluorescently labelled and then pulled into microfluidic channels precoated with either MAdCAM-1 or VCAM-1 as substrates. Interactions between leukocytes and substrates was recorded and analysed by cell tracking software. Cell kinetic parameters were calculated and used for the assessment of α4β7 and α4β1 integrin activity. Mn2+ was applied as activator to assess the full potential of integrin activity. Bio-naive CD patients were recruited and all received VDZ as treatment. Treatment response was assessed at week 14 by endoscopy. Patients were classified as primary loss of response to VDZ if the simplified endoscopic score for CD at week 14 failed to decrease by 25% compared to baseline. Blood samples were collected at weeks 0 (prior to VDZ infusion), 2, 6 and 14 and then applied for LAFA. The differences in α4β7 and α4β1 integrin activity between VDZ responders and non-responders were prospectively assessed and a prediction model was subsequently established.

Results
A total of 27 patients were recruited and received VDZ. Twenty patients were classified as responders and seven as non-responders. No difference was found in α4β7 integrin activity on CD4 and CD8 cells between responders and non-responders, either before or after VDZ treatment. However, a lower α4β1 integrin activity was found on CD4 and CD8 cells among VDZ non-responders at week 0 compared with responders in the presence of Mn2+. Using the best LAFA-derived markers, a model to predict VDZ non-responders at week 0 was developed, in which a sensitivity of 0.90 and a specificity of 0.73 were achieved, a substantially better performance than the existing prediction tool CDST. In addition, α4β1 integrin activity on CD4 and CD8 cells among non-responders was gradually enhanced following subsequent VDZ treatment, which was not detected in responders (figure), implying a possible mechanism underlining primary loss of response to VDZ.

Conclusion
Patients with a low α4β1 integrin activity at week 0 which can be enhanced after VDZ, is likely to be primary non-responders to VDZ. Integrin activity measured by LAFA prior to treatment may be used as new diagnostic tool for the prediction VDZ response in bio-naïve CD patients.

References
Dulai PS, Boland BS, Singh S, et al. Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn’s Disease. Gastroenterology. 2018;155(3):687-695.e10. doi:10.1053/j.gastro.2018.05.039