Background & aims: Vedolizumab (VDZ) is a monoclonal antibody directed against α4β7 integrin heterodimer, approved for patients with inflammatory bowel diseases (IBD). This study aimed at identifying immunological variables associated with response to vedolizumab in patients with ulcerative colitis (UC) and Crohn's disease (CD). Methods: This is a phase-IV explorative prospective interventional trial. IBD patients received open-label VDZ at weeks 0, 2, 6 and 14. Patients with a clinical response at week 14 were maintained with VDZ up to week 54. At week 0 and 14 their peripheral blood was obtained and endoscopy with biopsies was performed. The week-14 clinical response and remission, week-54 clinical remission, and week-14 endoscopic response were evaluated as endpoints of the study. The expression of surface markers, chemokine receptors and α4β7 heterodimer on peripheral blood and lamina propria lymphocytes was assessed by flow cytometry. A panel of soluble mediators were assessed in sera at baseline and at week 14 by 45-plex. Results: 38 IBD patients (20 UC, 18 CD) were included in the study. At week 14, the clinical response and remission rates were 87% and 66%, respectively. Higher baseline levels of circulating memory Th1 cells were strongly associated with clinical response at week 14 (P=0.0001), while reduced baseline levels of lamina propria memory Th17 and Th1/17 cells were associated with endoscopic response. Immunological clusters were found to be independently associated with vedolizumab outcomes at multivariable analysis. A panel of soluble markers, including IL17A, TNF, CXCL1, CCL19 for CD and G-CSF and IL7 for UC, associated with vedolizumab-induced week-54 clinical remission. Conclusions: The results of this exploratory study uncovered a panel of circulating and mucosal immunological variables associated with response to treatment by vedolizumab treatment.

Immunological variables associated with clinical and endoscopic response to vedolizumab in patients with inflammatory bowel diseases / M. Coletta, M. Paroni, M.F. Alvisi, M. De Luca, E. Rulli, S. Mazza, F. Facciotti, G. Lattanzi, F. Strati, S. Abrignani, M.C. Fantini, M. Vecchi, J. Geginat, F. Caprioli. - In: JOURNAL OF CROHN'S AND COLITIS. - ISSN 1873-9946. - 14:9(2020 Sep), pp. 1190-1201. [10.1093/ecco-jcc/jjaa035]

Immunological variables associated with clinical and endoscopic response to vedolizumab in patients with inflammatory bowel diseases

M. Paroni
Secondo
;
S. Mazza;G. Lattanzi;S. Abrignani;M. Vecchi;J. Geginat
Penultimo
;
F. Caprioli
Ultimo
2020

Abstract

Background & aims: Vedolizumab (VDZ) is a monoclonal antibody directed against α4β7 integrin heterodimer, approved for patients with inflammatory bowel diseases (IBD). This study aimed at identifying immunological variables associated with response to vedolizumab in patients with ulcerative colitis (UC) and Crohn's disease (CD). Methods: This is a phase-IV explorative prospective interventional trial. IBD patients received open-label VDZ at weeks 0, 2, 6 and 14. Patients with a clinical response at week 14 were maintained with VDZ up to week 54. At week 0 and 14 their peripheral blood was obtained and endoscopy with biopsies was performed. The week-14 clinical response and remission, week-54 clinical remission, and week-14 endoscopic response were evaluated as endpoints of the study. The expression of surface markers, chemokine receptors and α4β7 heterodimer on peripheral blood and lamina propria lymphocytes was assessed by flow cytometry. A panel of soluble mediators were assessed in sera at baseline and at week 14 by 45-plex. Results: 38 IBD patients (20 UC, 18 CD) were included in the study. At week 14, the clinical response and remission rates were 87% and 66%, respectively. Higher baseline levels of circulating memory Th1 cells were strongly associated with clinical response at week 14 (P=0.0001), while reduced baseline levels of lamina propria memory Th17 and Th1/17 cells were associated with endoscopic response. Immunological clusters were found to be independently associated with vedolizumab outcomes at multivariable analysis. A panel of soluble markers, including IL17A, TNF, CXCL1, CCL19 for CD and G-CSF and IL7 for UC, associated with vedolizumab-induced week-54 clinical remission. Conclusions: The results of this exploratory study uncovered a panel of circulating and mucosal immunological variables associated with response to treatment by vedolizumab treatment.
IBD; T-cell subsets; vedolizumab
Settore MED/12 - Gastroenterologia
Settore MED/04 - Patologia Generale
26-feb-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/720773
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