Lieven Pouillon1,2, Hélène Rousseau3, Hélène Busby-Venner4, Marcelo De Carvalho Bittencourt5, Myriam Choukour1, Guillaume Gauchotte4, Camille Zallot1, Silvio Danese6, Cédric Baumann3, Laurent Peyrin-Biroulet1. 1. INSERM U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France. 2. Imelda GI Clinical Research Centre, Imeldaziekenhuis Bonheiden, Bonheiden, Belgium. 3. Clinical Research Support Facility PARC, UMDS, Nancy University Hospital, Vandoeuvre-lès-Nancy, France. 4. Department of Pathology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France. 5. IMOPA UMR 7365 and Department of Immunology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France. 6. Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy.
Abstract
BACKGROUND AND AIMS: Histological healing may be the ultimate therapeutic goal in ulcerative colitis [UC]. We investigated, for the first time, the association between vedolizumab trough levels and histological healing in UC. METHODS: This is a single-centre retrospective cohort study including all consecutive UC patients on vedolizumab maintenance therapy who had a histological evaluation blindly to clinical data and underwent therapeutic drug monitoring, between June 2014 and March 2018. Per-event analysis was performed. Histological healing was defined as a Nancy histological index ≤1. RESULTS: Thirty-five histological samples were analysed. Median [interquartile range] vedolizumab trough levels were higher in the group with histological healing (31.5 [25-49.1] μg/mL) compared with the group without histological healing (15 [9-26.6] μg/mL, p = 0.02). The higher vedolizumab trough level quartiles tended to be associated with greater rates of histological healing [p = 0.10]. A cut-off vedolizumab trough level of 25 μg/mL predicted histological healing with an accuracy of 74% and an area under the receiver operating curve of 0.62 [95% confidence interval 0.58-0.92, p = 0.004]. Bivariate analysis identified a vedolizumab trough level ≥25 µg/mL [p = 0.006], a partial Mayo score ≤1 [p = 0.008], C-reactive protein level <5 mg/L [p = 0.005] and a Mayo endoscopic subscore ≤1 [p = 0.0004] as factors associated with histological healing. CONCLUSIONS: Histological healing was associated with higher vedolizumab trough levels during maintenance therapy in UC. A vedolizumab trough level threshold of 25 μg/mL proved most optimal to predict histological healing according to the Nancy histological index. Confirmation of these data in larger, independent cohorts is needed.
BACKGROUND AND AIMS: Histological healing may be the ultimate therapeutic goal in ulcerative colitis [UC]. We investigated, for the first time, the association between vedolizumab trough levels and histological healing in UC. METHODS: This is a single-centre retrospective cohort study including all consecutive UC patients on vedolizumab maintenance therapy who had a histological evaluation blindly to clinical data and underwent therapeutic drug monitoring, between June 2014 and March 2018. Per-event analysis was performed. Histological healing was defined as a Nancy histological index ≤1. RESULTS: Thirty-five histological samples were analysed. Median [interquartile range] vedolizumab trough levels were higher in the group with histological healing (31.5 [25-49.1] μg/mL) compared with the group without histological healing (15 [9-26.6] μg/mL, p = 0.02). The higher vedolizumab trough level quartiles tended to be associated with greater rates of histological healing [p = 0.10]. A cut-off vedolizumab trough level of 25 μg/mL predicted histological healing with an accuracy of 74% and an area under the receiver operating curve of 0.62 [95% confidence interval 0.58-0.92, p = 0.004]. Bivariate analysis identified a vedolizumab trough level ≥25 µg/mL [p = 0.006], a partial Mayo score ≤1 [p = 0.008], C-reactive protein level <5 mg/L [p = 0.005] and a Mayo endoscopic subscore ≤1 [p = 0.0004] as factors associated with histological healing. CONCLUSIONS: Histological healing was associated with higher vedolizumab trough levels during maintenance therapy in UC. A vedolizumab trough level threshold of 25 μg/mL proved most optimal to predict histological healing according to the Nancy histological index. Confirmation of these data in larger, independent cohorts is needed.
Authors: Konstantinos Papamichael; Adam S Cheifetz; Gil Y Melmed; Peter M Irving; Niels Vande Casteele; Patricia L Kozuch; Laura E Raffals; Leonard Baidoo; Brian Bressler; Shane M Devlin; Jennifer Jones; Gilaad G Kaplan; Miles P Sparrow; Fernando S Velayos; Thomas Ullman; Corey A Siegel Journal: Clin Gastroenterol Hepatol Date: 2019-03-27 Impact factor: 11.382
Authors: Patrizio Scarozza; Irene Marafini; Federica Laudisi; Edoardo Troncone; Heike Schmitt; Marco Vincenzo Lenti; Stefania Costa; Irene Rocchetti; Elena De Cristofaro; Silvia Salvatori; Ludovica Frezzati; Antonio Di Sabatino; Raja Atreya; Markus F Neurath; Emma Calabrese; Giovanni Monteleone Journal: J Clin Med Date: 2020-02-01 Impact factor: 4.241
Authors: Britt Christensen; Stephen B Hanauer; Peter R Gibson; Jerrold R Turner; John Hart; David T Rubin Journal: J Crohns Colitis Date: 2020-10-05 Impact factor: 10.020