Parambir S Dulai1, Emily C L Wong2, Walter Reinisch3, Jean-Frederic Colombel4, John K Marshall2, Neeraj Narula2. 1. Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. 2. Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton ON, Canada. 3. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. 4. Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND & AIMS: We have previously validated a clinical decision support tool (CDST) (vedolizumab CDST [VDZ-CDST]) for clinical and endoscopic remission with VDZ in ulcerative colitis (UC). We aim to expand the validation for predicting histoendoscopic mucosal improvement (HEMI) with VDZ vs adalimumab (ADA). METHODS: In a post hoc analysis of a clinical trial for VDZ vs ADA in moderate to severe UC (VARSITY trial; NCT02497469), comparative accuracy was evaluated for the VDZ-CDST among an external validation cohort of VDZ- and ADA-treated patients for week 52 HEMI (Mayo endoscopic subscore 0-1 and Geboes score <3.2). Comparative effectiveness of VDZ and ADA was assessed after stratifying the cohort by baseline probability of response to VDZ using the VDZ-CDST. RESULTS: A total of 419 patients were included. The majority of patients enrolled in the VARSITY trial had a high (61%) or intermediate (29%) baseline predicted probability of response to VDZ. The baseline VDZ-CDST score was significantly more likely to predict week 52 HEMI for VDZ (area under the curve , 0.712; 95% confidence interval, 0.636-0.787) relative to ADA-treated patients (area under the curve, 0.538; 95% confidence interval, 0.377-0.700; P < .001 for AUC comparison). A significant (P < .001) association was observed between the VDZ-CDST and measured VDZ drug exposure over 52 weeks. Superiority of VDZ to ADA was only observed in patients with a high baseline predicted probability of response to VDZ. CONCLUSIONS: Superiority of VDZ to ADA is dependent on baseline probability of response, and a VDZ-CDST is capable of identifying UC patients most appropriate for VDZ vs ADA.
BACKGROUND & AIMS: We have previously validated a clinical decision support tool (CDST) (vedolizumab CDST [VDZ-CDST]) for clinical and endoscopic remission with VDZ in ulcerative colitis (UC). We aim to expand the validation for predicting histoendoscopic mucosal improvement (HEMI) with VDZ vs adalimumab (ADA). METHODS: In a post hoc analysis of a clinical trial for VDZ vs ADA in moderate to severe UC (VARSITY trial; NCT02497469), comparative accuracy was evaluated for the VDZ-CDST among an external validation cohort of VDZ- and ADA-treated patients for week 52 HEMI (Mayo endoscopic subscore 0-1 and Geboes score <3.2). Comparative effectiveness of VDZ and ADA was assessed after stratifying the cohort by baseline probability of response to VDZ using the VDZ-CDST. RESULTS: A total of 419 patients were included. The majority of patients enrolled in the VARSITY trial had a high (61%) or intermediate (29%) baseline predicted probability of response to VDZ. The baseline VDZ-CDST score was significantly more likely to predict week 52 HEMI for VDZ (area under the curve , 0.712; 95% confidence interval, 0.636-0.787) relative to ADA-treated patients (area under the curve, 0.538; 95% confidence interval, 0.377-0.700; P < .001 for AUC comparison). A significant (P < .001) association was observed between the VDZ-CDST and measured VDZ drug exposure over 52 weeks. Superiority of VDZ to ADA was only observed in patients with a high baseline predicted probability of response to VDZ. CONCLUSIONS: Superiority of VDZ to ADA is dependent on baseline probability of response, and a VDZ-CDST is capable of identifying UC patients most appropriate for VDZ vs ADA.
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Authors: Parambir S Dulai; Siddharth Singh; Niels Vande Casteele; Joseph Meserve; Adam Winters; Shreya Chablaney; Satimai Aniwan; Preeti Shashi; Gursimran Kochhar; Aaron Weiss; Jenna L Koliani-Pace; Youran Gao; Brigid S Boland; John T Chang; David Faleck; Robert Hirten; Ryan Ungaro; Dana Lukin; Keith Sultan; David Hudesman; Shannon Chang; Matthew Bohm; Sashidhar Varma; Monika Fischer; Eugenia Shmidt; Arun Swaminath; Nitin Gupta; Maria Rosario; Vipul Jairath; Leonardo Guizzetti; Brian G Feagan; Corey A Siegel; Bo Shen; Sunanda Kane; Edward V Loftus; William J Sandborn; Bruce E Sands; Jean-Frederic Colombel; Karen Lasch; Charlie Cao Journal: Clin Gastroenterol Hepatol Date: 2020-02-13 Impact factor: 11.382