Vedolizumab Maintenance Therapy for Crohnʼs Disease: Results of GEMINI II, a Randomized, Placebo-Controlled, Double-Blind, Multi-center Phase 3 Trial (2012)

Purpose: To assess the efficacy and safety of vedolizumab (VDZ), a gut-selective monoclonal antibody targeting α4β7 integrin, for maintaining response and remission in patients with moderate to severely active Crohn's disease (CD) with evidence of clinical response after two 300 mg IV induction doses of VDZ. Methods: Eligible adult patients entered the induction phase with a CDAI score of 220-450 and objective evidence of active CD, despite prior treatment with corticosteroids (CS), purine antimetabolites and/or TNFα antagonists. Patients responding (≥70-point decrease in CDAI from baseline) at wk 6 to induction treatment with vedolizumab were randomized 1:1:1 to VDZ 300 mg IV every 4 wks, every 8 wks, or placebo for 44 wks. The primary outcome was remission (CDAI ≤150 points) at 52 wks. Secondary outcomes were enhanced response (≥100-point CDAI decrease) and CS-free remission at 52 wks, and durability of remission (remission at ≥80% of visits including the final visit). Results: Of 1115 patients who received induction treatment, 461 (mean age: 35.7 yrs, mean disease duration: 8.6 yrs, mean CDAI at wk 6: 180.6) met response criteria at 6 wks (ITT population) and were randomized to receive VDZ q8wks (n=154), VDZ q4wks (n=154), or placebo (n=153). 51% of the ITT population had prior anti-TNFα failure; 45% had no anti-TNFα exposure. A significantly greater proportion of VDZ-treated patients than placebo-treated patients had clinical remission, enhanced response, and CS free remission at 52 wks; a numerical trend without statistical significance was seen in durable remission (Table 1). Remission rates were greater for patients assigned to VDZ than those who received placebo, irrespective of prior anti-TNF treatment status (Table 2). In the safety population (N=1115) for wks 0-52, exposure-adjusted rates of all adverse events (AEs) were comparable across treatment groups. In the ITT population, exposure-adjusted rates of serious infections were comparable across treatment groups, while exposure-adjusted rates of serious AEs were higher in the placebo arm than VDZ groups.Table 1: Clinical remission, enhanced clinical response, corticosteroid-free remission, and durability of clinical remission, ITT population ( n =461)Table 2: Clinical remission and enhanced clinical response at 52 weeks in patients with prior anti-TNF failure or without anti-TNF exposure, ITT populationaConclusion: In this treatment refractory population, patients who received maintenance therapy with VDZ every 4 or 8 wks had significantly higher rates of remission, enhanced response, and CS-free remission than those assigned to placebo in CD patients who had failed immunosuppressives and/or TNF antagonists. Exposure-adjusted serious infection rates were comparable among treatment groups in the ITT population. Disclosure: This study was supported by Millennium Pharmaceuticals, Inc. Dr. Hanauer - Consultant and Advisory Boards, Takeda Pharmaceuticals; Dr. Colombel - Consultant, Takeda Pharmaceuticals; Dr. Feagan - Grant/Research Support, Merck, Otsuka, Milllennium, Tillotts, Abbott, Protein Design Labs, Boehringer Engelheim, Novartis, Centocor, Berlex, Synta, Elan/Biogen, UCB Pharma, BMS, Proctor and Gamble, Osiris, Genentech, CombinatoRx, ActoGeniX, Wyeth, Consultant, Synta, Millennium, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Protein Design Labs, ISIS, Teva Pharmaceuticals, Santarus, Bristol-Myers Squibb, Celgene, Combinatorx, UCB Pharma, Napo Pharma, Abbott, Proctor and Gamble, Osiris, Berlex, Astra Zeneca, GeneLogic Inc. Cerimon Pharm., Tioga Pharm, Serono, Genentech, Tillotts, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharm., Ore Pharm. (previously GeneLogic), Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Alba Therapeutics, Axcan, Funxional Therapeutics, Gilead, Nektar, Pfizer, Shire, Wyeth, Zealand Pharm, Zyngenia, gICare Pharma Inc., Speakers Bureau, UCB, Abbott, J&J/Janssen, Advisory Boards, Astra Zeneca, Elan/Biogen, Celltech, Merck, Celgene, Novartis, Given Imaging Inc., UCB Pharma, Salix Pharmaceuticals, Abbott Laboratories, Centocor Inc. Pfizer, Axcan, Tillotts Pharma AG, Prometheus Laboratories; Dr. Rutgeerts - Consultant/Lectures/Research Support, Centocor, Merck, UCB, Abbott, Genentech/Roche, Pfizer, Hoffmann-LaRoche, Bristol Myers Squibb, Tillotts, GSK, chemoCentryx, Neovacs, Millennium Pharmaceuticals and Takeda Pharmaceuticals; Dr. Sandborn - Consultant and Grant/Research Support, Millennium Pharmaceuticals and Takeda Pharmaceuticals; Dr. Sands - Consultant and Grant/Research Support, Takeda Pharmaceuticals; Dr. Fedorak - Grant/Research Support, Millennium Pharmaceuticals; Dr. Lee - Grant/Research Support, Abbott Pharmaceuticals, UCB Pharma, Pfizer, Salix Pharmaceuticals, Millennium Pharmaceuticals, Centocor Inc., Prometheus Laboratories, Glaxo-SmithKline, Speakers Bureau, Abbott Pharmaceuticals, UCB Pharma, Centocor Inc. Consultant, Abbott Pharmaceuticals, UCB Pharma, Centocor Inc; Drs. Fox, Xu, Sankoh, and Milch, and Ms. Stephens - Employees, Millennium Pharmaceuticals; Dr. Parikh - Employee, Takeda Pharmaceuticals International; Drs. Lukas and Bressler - no relationships to disclose.