P319a Deep clinical remission in patients with Ulcerative Colitis: Evaluating the effects of vedolizumab on various combinations of endoscopic and patient-reported outcomes
W. Sandborn*1, J.-F. Colombel2, R. Panaccione3, K. Lasch4, S. Sankoh5, B. Abhyankar6
1University of California San Diego, Division of Gastroenterology, La Jolla, United States, 2Icahn School of Medicine at Mount Sinai, The Dr. Henry D. Janowitz Division of Gastroenterology, New York, United States, 3University of Calgary, Department of Medicine, Calgary, Canada, 4Takeda Pharmaceuticals International, Inc., GI Medical Affairs, US Region, Deerfield, United States, 5Takeda Pharmaceuticals International Co., Global Statistics, Cambridge, United States, 6Takeda Global Research & Development Centre (Europe) Ltd., GI Clinical Science, London, United Kingdom
The evolving concept of deep clinical remission in the treatment of ulcerative colitis (UC) involves both endoscopic outcomes and patient-reported outcomes (PROs). The purpose of the current post hoc analyses of data from the GEMINI 1 induction and maintenance phases  was to evaluate the effects of vedolizumab (VDZ) on deep remission using various combinations of endoscopic outcomes (Mayo Clinic endoscopy subscore [ES]) and PROs (Mayo Clinic symptom subscores).
At wks 0 and 2 of the GEMINI 1 induction phase (wks 0-6), patients in cohort 1 received randomly assigned, blinded VDZ 300 mg or placebo (PBO), and patients in cohort 2 received open-label VDZ 300 mg. At wk 6, VDZ responders were randomly assigned to receive VDZ 300 mg every 8 wks (Q8W) or every 4 wks (Q4W) or PBO in the maintenance phase (wks 6-52). At wks 6 and 52, the following 4 post hoc deep remission end points, defined using endoscopic outcomes and PROs, were evaluated: (1) endoscopic remission (ES = 0) and symptomatic improvement (rectal bleeding subscore [RBS] = 0, stool frequency subscore [SFS] decrease or no change from baseline); (2) endoscopic improvement (ES ≤1) and symptomatic remission (RBS = 0, SFS = 0); (3) total score (ES + RBS + SFS) ≤1 with endoscopic and symptomatic improvement (ES≤ 1, RBS = 0, SFS decrease or no change from baseline); and (4) endoscopic and symptomatic improvement (ES ≤1, RBS = 0, SFS ≤1).
At wk 0, mean UC duration was 6.2 y (Q8W), 7.6 y (Q4W), and 7.8 y (PBO); mean complete Mayo Clinic scores were 8.4 (Q8W), 8.3 (Q4W), and 8.4 (PBO); and 36% (Q8W), 32% (Q4W), and 30% (PBO) of patients had prior tumor necrosis factor antagonist failure. Rates of deep remission were significantly higher with VDZ than PBO (Table 1) for all end points at wks 6 and 52 (except endoscopic remission and symptomatic improvement at wk 6). Safety data from the GEMINI 1 induction and maintenance phases have been previously described. 
In patients with UC, VDZ led to statistically significant and clinically meaningful improvements at wk 6 for 3 of 4 deep remission end points, defined using various combinations of endoscopic outcomes and PROs, and at wk 52 for all 4 end points.
Clinical study was funded by Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.). Medical writing assistance was provided by Stefanie Dorlas of MedLogix Communications, LLC, and supported by Takeda Pharmaceuticals International, Inc.
 Feagan BG, et al., (2013), Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis, N. Engl J Med., 699-710