IMMUNOLOGIC PREDICTORS OF RESPONSE TO VEDOLIZUMAB TREATMENT IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: RESULTS OF A PHASE IV PROSPECTIVE INTERVENTIONAL TRIAL

Objective: Vedolizumab (VDZ) is a monoclonal antibody directed against α4β7 integrin heterodimer, approved for patients with inflammatory bowel disease (IBD). This study aimed at identifying circulating and mucosal immunologic predictors of response in patients with active ulcerative colitis (UC) and Crohn’s disease (CD). Design: This is an explorative, prospective, phase IV interventional trial (Eudract n. 2015- 003270-32). Consecutive CD and UC patients received open-label VDZ at weeks 0, 2, 6 and 14. A week 10 infusion was performed in CD patients. Patients with clinical response at week 14 were maintained with VDZ every 8 weeks up to 54 weeks. At week 0 and 14 peripheral blood was obtained and endoscopy with biopsies was performed. The expression of surface markers, chemokine receptors and α4β7 heterodimer on peripheral blood and lamina propria lymphocytes was assessed by flow cytometry. Results: 38 IBD patients (20 UC, 18 CD) were included in the study. At week 14, clinical response and remission rates were 87% and 66%, respectively. Endoscopic response rate was 47%. Among week 14 responders, clinical remission rate at week 54 was 69%. No clinical variables were found to predict either clinical or endoscopic outcomes. On the contrary, higher baseline levels of circulating memory CXCR3+CCR6- CD4+ T cells (Th1 cells) were strongly associated with week 14 clinical response (P=0.0001). Reduced baseline levels of lamina propria memory CXCR3-CCR6+ CD4+ T cells (Th17 cells) and CXCR3+CCR6+ CD4+ T cells (Th1/17 cells) were predictive of endoscopic response (P=0.012 and P=0.005 respectively). Circulating levels of Th1 memory T cells predicted clinical remission in IBD patients at week 54. Conclusions: The results of this exploratory study uncovered a panel of circulating and mucosal immunological predictors of response to vedolizumab treatment. These data provide further insights on the mechanism of action of vedolizumab in IBD patients.