Vedolizumab Induction Therapy for Crohnʼs Disease: Results of Gemini II, a Randomized, Placebo-Controlled, Double-Blind, Multicenter Phase 3 Trial (2012)

Purpose: To assess the efficacy and safety of vedolizumab, a gut-selective monoclonal antibody targeting α4β7 integrin, as induction therapy in patients with moderate to severely active Crohn's disease (CD). Methods: 368 patients with a Crohn's disease activity index (CDAI) of 220-450 and either C-reactive protein (CRP) >2.87, colonoscopy photo of active CD within 4 months prior to randomization, or fecal calprotectin >250 μg/g stool at screening plus CT, MR, xray, or endoscopic evidence of CD within 4 months prior to screening, despite treatment with corticosteroids, purine antimetabolites and/or TNFα antagonists, were randomized 3:2 to receive either vedolizumab 300 mg IV or placebo on days 1 and 15. Primary outcomes were clinical remission (CDAI score ≤150 points) and enhanced clinical response (≥100-point decrease in CDAI from baseline) at 6 weeks tested simultaneously (Hochberg method to control for multiple testing). A secondary outcome was mean change in serum CRP at 6 weeks in patients with elevated CRP at baseline. Results: The intent-to-treat (ITT) population comprised 368 patients (mean age 37.2 yrs; mean disease duration 8.8 yrs; mean baseline CDAI score 326.2). Of these, 220 received vedolizumab, and 148 received placebo. 48% of the ITT population had prior anti-TNFα failure; of these 55% were primary failures (26% of total ITT population). In addition, 27% of the ITT population had failed at least 2 TNF antagonists. A significantly greater proportion of vedolizumab than placebo patients achieved clinical remission at 6 weeks (Table 1). At the 6 week timepoint, no significant difference was observed in the rates of enhanced clinical response or change in CRP between the vedolizumab and placebo groups. In pre-specified subgroup analyses, positive trends were observed for clinical remission and enhanced clinical response rates in vedolizumab versus placebo patients irrespective of prior anti-TNF treatment status (Table 2). In analyses through week 6, rates of adverse events (AEs), serious AEs, and serious infectious AEs were similar between treatment groups.Table 1: Primary and secondary outcomes, ITT populationTable: [1550] Table 2. Clinical remission and enhanced clinical response at 6 weeks in patients with prior anti-TNF failure or without anti-TNF exposure, ITT populationConclusion: Vedolizumab induction therapy was significantly more effective than placebo in achieving clinical remission at 6 weeks in a population with highly active CD, most of whom had failed immunosuppressives, at least 1 prior anti-TNF therapy, or a combination of the two. Disclosure: This study was supported by Millennium Pharmaceuticals, Inc. Dr. Sandborn - Consultant and Grant/Research Support, Millennium Pharmaceuticals and Takeda Pharmaceuticals; Dr. Sands - Consultant and Grant/Research Support, 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. Fedorak - Grant/Research Support, Millennium Pharmaceuticals; Dr. Lee - Grant/Research Support, Abbott Pharmaceuticals, UCB Pharma, Pfizer, Salix Pharmaceuticals, Millennium Pharmaceuticals, Centocor Inc., Prometheus Laboratories, GlaxoSmithKline, Speakers Bureau, Abbott Pharmaceuticals, UCB Pharma, Centocor Inc. Consultant, Abbott Pharmaceuticals, UCB Pharma, Centocor Inc; Drs. Xu, Sankoh, Fox, and Milch, and Ms. Stephens - Employees, Millennium Pharmaceuticals; Dr. Parikh - Employee, Takeda Pharmaceuticals International; Drs. Lukas and Bressler - no relationships to disclose.