P209 Long-term effectiveness and safety of vedolizumab in patients with ulcerative colitis: 5-year cumulative exposure of GEMINI 1 completers rolling into the GEMINI open-label extension study
Loftus E.V.1, Colombel J.-F.2, Feagan B.3, Vermeire S.*4, Sandborn W.5, Sands B.6, Danese S.7, D'Haens G.8, Kaser A.9, Panaccione R.10, Rubin D.11, Shafran I.12, O'Byrne S.13, Geransar P.13, James A.14, Kaviya A.15, Khalid J.M.16
1Mayo Clinic College of Medicine, Gastroenterology and Hepatology, Rochester, United States 2Icahn School of Medicine at Mount Sinai, Gastroenterology, New York, United States 3Robarts Research Institute, University of Western Ontario, Robarts Clinical Trials, London, Canada 4University hospitals Leuven, Department of clinical and experimental medicine, Leuven, Belgium 5University of California - San Diego, Division of Gastroenterology, La Jolla, United States 6Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, New York, United States 7Humanitas University, Italy, Gastrointestinal Immunopathology, Milan, Italy 8Academic Medical Centre, Dept. of Gastroenterology, Amsterdam, Netherlands 9University of Cambridge, Division of Gastroenterology and Hepatology, Cambridge, United Kingdom 10University of Calgary, Department of Medicine, Calgary, Canada 11University of Chicago Medicine Inflammatory Bowel Disease Center, Section of Gastroenterology, Hepatology, and Nutrition, Chicago, United States 12Shafran Gastroenterology Research center, Gastroenterology, Winter Park, United States 13Takeda Pharmaceuticals International AG, Global Medical Affairs, Zurich, Switzerland 14Takeda Development Centre Europe Ltd, Global Statistics and Statistical Programming, London, United Kingdom 15Takeda Development Centre Europe Ltd, Clinical Development, London, United Kingdom 16Takeda Development Centre Europe Ltd, Evidence and Value Generation, London, United Kingdom
Approval of vedolizumab (VDZ) for moderately to severely active ulcerative colitis (UC) was based on the phase 3 GEMINI 1 study.  The GEMINI open-label extension (OLE) trial is an ongoing study investigating the long-term safety of VDZ (NCT00790933). Here we report the 5-year exploratory analyses of effectiveness and safety in patients (pts) with UC who had completed GEMINI 1 and were enrolled in GEMINI OLE.
Analyses included pts who responded to VDZ induction at Week (Wk) 6 and had received VDZ maintenance (every 8 or 4 wks; data were combined) to Wk 52 of GEMINI 1, followed by VDZ every 4 wks in GEMINI OLE. Pts with 248 wks of cumulative VDZ treatment (data were collected from 22 May 2009 to 21 May 2015) were assessed for clinical response (decrease in partial Mayo Score [PMS] of ≥2 points and ≥25% change from baseline [BL], with an accompanying decrease in rectal bleeding subscore of ≥1 point from BL or absolute rectal bleeding subscore of ≤1 point), clinical remission (PMS of ≤2 with no individual subscore >1) and health-related quality of life (HRQoL), including IBD Questionnaire (IBDQ) and Euro Quality of Life-5D visual analogue scale (EQ-5D VAS). Safety was also assessed.
Of 247 pts in GEMINI 1 who responded to VDZ induction at Wk 6 and received VDZ in maintenance, 154 (62%) completed VDZ maintenance and were enrolled in GEMINI OLE (anti-TNFα-naïve n=107; anti-TNFα failure n=42). At the time of this analysis, 63 pts had completed 248 wks of cumulative VDZ treatment; 54 had discontinued (n=19 [35%] due to lack of continued benefit) and 37 are ongoing (have not yet reached 248 wks of treatment). Of pts with data at Wk 248 (n=63), 98% had clinical response and 90% were in remission (Table). HRQoL improvements were observed at Wk 248, with mean change from BL IBDQ and EQ-5D-VAS scores of 58.7 and 24.0, respectively. In the safety population, 137 pts had adverse (AEs); 17 discontinued due to AEs. Serious AEs were reported in 44 pts (in 7 pts these were drug-related; 8 pts discontinued as a consequence of serious AEs). No deaths were reported.
In UC patients who were responders at Wk 6 of GEMINI 1 (who continued to respond during the study), long-term VDZ therapy (∼5 years) was associated with clinical benefits including clinical response, clinical remission and HRQoL improvements. The safety profile was consistent with that previously observed in a 3-year interim analysis of the OLE study.
 Feagan BG, Rutgeerts P, Sands BE, et al. (2013), Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis, N Engl J Med, 699–710