Laurent Peyrin-Biroulet, MD, PhD1, Jean-Frédéric Colombel, MD2, Edward V. Loftus, Jr., MD, FACG3, Silvio Danese, MD, PhD4, Brihad Abhyankar, FRCS, MBA5, Jingjing Chen, PhD6, Raquel Rogers, MD, MSc6, Richard A. Lirio, MD6, Jeffrey D. Bornstein, MD6, Bruce E. Sands, MD, FACG7, Stefan Schreiber, MD, PhD8
1Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; 2Icahn School of Medicine at Mount Sinai Hospital, New York, NY; 3Mayo Clinic, Rochester, MN; 4Humanitas University, Milan, Lombardia, Italy; 5Takeda, London, UK, Dublin, Dublin, Ireland; 6Takeda Development Center Americas, Inc., Cambridge, MA; 7Icahn School of Medicine at Mount Sinai, New York, NY; 8Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany
Introduction: Histologic remission is associated with superior long-term clinical outcomes in ulcerative colitis (UC). VARSITY, the first head-to-head comparison of biologic agents in UC (NCT02497469; EudraCT 2015-000939-33), showed superior clinical remission and endoscopic improvement at Week 52 with vedolizumab (VDZ), a gut-selective, humanized, α4β7 integrin monoclonal antibody, vs adalimumab (ADA), a systemic, human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody.1 Both VDZ and ADA were generally safe and well-tolerated.1 This analysis compared histologic improvements with VDZ vs ADA in VARSITY.
Methods: Patients with moderately to severely active UC were randomized 1:1 to active VDZ intravenous (IV) infusions (300 mg)/placebo subcutaneous (SC) injections or placebo IV/active ADA SC (160/80/40 mg). Prespecified histologic exploratory endpoints included histologic remission (Geboes score < 2 or Robarts Histopathology Index [RHI] score < 3) and minimal histologic disease activity (Geboes score < 3.2 or RHI score < 5) at Week 14 and Week 52. Histologic remission was also assessed based on previous anti-TNF use.
Results: A total of 769 patients received ≥1 dose of VDZ (n=383) or ADA (n=386). Median (range) duration of exposure was 477 (127, 630) days for VDZ and 420 (71, 454) days for ADA. Mean (standard deviation) baseline histologic disease activity was similar between groups (Geboes: VDZ, 15.0 [4.92]; ADA, 15.1 [5.03]; RHI: VDZ, 19.5 [8.74]; ADA, 19.6 [8.89]). Histologic remission induced by VDZ at Week 52 was greater than with ADA in the overall (Geboes or RHI), anti-TNF naïve (Geboes or RHI), and anti-TNF failure (RHI only) groups (Table). Histologic remission at Week 14 favored VDZ over ADA, with larger differentiation when using RHI (Table). VDZ also outperformed ADA in achieving minimal histologic disease activity at Weeks 14 and 52 (Table).
Discussion: VARSITY showed that use of VDZ, compared with ADA, achieved higher rates of histologic remission and minimal histologic disease activity at Weeks 14 and 52 in patients with moderately to severely active UC. These data support the use of VDZ over ADA in UC. Reference: 1. Schreiber S, et al. J Crohns Colitis. 2019;13(suppl 1):S612-S613. Abstract OP34.
Citation: Laurent Peyrin-Biroulet, MD, PhD; Jean-Frédéric Colombel, MD; Edward V. Loftus, Jr., MD, FACG; Silvio Danese, MD, PhD; Brihad Abhyankar, FRCS, MBA; Jingjing Chen, PhD; Raquel Rogers, MD, MSc; Richard A. Lirio, MD; Jeffrey D. Bornstein, MD; Bruce E. Sands, MD, FACG; Stefan Schreiber, MD, PhD. P1402 - HISTOLOGIC IMPROVEMENT WITH VEDOLIZUMAB VS. ADALIMUMAB IN ULCERATIVE COLITIS: RESULTS FROM VARSITY. Program No. P1402. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.