P1469 (S0664). - Disease Control and Changes in Individual Treatment Outcomes From Week 14 to Week 52 With Vedolizumab or Adalimumab in Ulcerative Colitis: A VARSITY Trial Post Hoc Analysis

Edward V. Loftus, Jr., MD, FACG¹, Silvio Danese, MD, PhD², Laurent Peyrin-Biroulet, MD³, Jean-Frederic Colombel⁴, Bruce E. Sands, MD, MS, FACG⁴, Dirk Lindner, MSc⁵, Richard A. Lirio, MD⁶, Christian Agboton, MD⁵, Stefan Schreiber⁷; ¹Mayo Clinic College of Medicine, Rochester, MN; ²Humanitas University, Milan, Lombardia, Italy; ³Nancy University Hospital, Nancy, Lorraine, France; ⁴Icahn School of Medicine at Mount Sinai, New York, NY; ⁵Takeda, Zurich, Zurich, Switzerland; ⁶Takeda, Cambridge, MA; ⁷University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

Introduction: In VARSITY, vedolizumab (VDZ), an anti-α₄β₇ integrin antibody, achieved superior clinical, endoscopic and histologic outcomes vs adalimumab (ADA), an anti-tumor necrosis factor (TNF) agent, in patients with moderate-to-severe ulcerative colitis (UC).¹ In recent years, the therapeutic goal for UC has evolved from symptom relief to disease control across multiple outcomes.

Methods: This VARSITY post hoc analysis evaluated the trajectory of UC key endpoints and disease control with intravenous VDZ vs subcutaneous ADA between early (Week [W]14) and late (W52) time points. Evolution in disease control over time was assessed based on the proportion of patients who maintained, improved or lost treatment benefit from W14 to W52 for the efficacy endpoints clinical remission, endoscopic and histologic improvement (defined in Figure). Data were analyzed within treatment arms in the full analysis population and by prior anti-TNF use (anti-TNF naïve or experienced). Observed data were reported without imputation.

Results: The study included 769 patients with UC (386 ADA, 383 VDZ). Most patients (56.0% ADA vs 60.8% VDZ) were male, were not using a corticosteroid at baseline (63.7% vs 63.9%) and were anti-TNF naïve (79.0% vs 79.2%). Median UC duration was 4.5 (ADA) and 4.8 (VDZ) years. At W14 and W52, clinical remission, endoscopic and histologic improvement, and disease control were all achieved more frequently with VDZ vs ADA (Table). More patients maintained each efficacy outcome and disease control from W14 to W52 with VDZ vs ADA, in both anti-TNF subgroups (Figure). In both arms, more anti-TNF naïve than anti-TNF experienced patients maintained efficacy (Figure). The numbers of patients who gained efficacy at W52 were more comparable between anti-TNF naïve and experienced. At W52, the overall rate of disease control was higher with VDZ (47.3% anti-TNF naïve vs 39.0% anti-TNF experienced) than ADA (32.7% vs 24.2%) (Table). Further analyses of early predictors of late disease control will be presented.

Discussion: VDZ treatment maintains greater early disease control than ADA in moderate-to-severe UC from W14 to W52, especially in anti-TNF naïve patients. These data suggest that VDZ is superior to ADA during both induction treatment evaluated at W14 and maintenance treatment evaluated at W52. Most of the observed treatment differences in anti-TNF naïve patients at W52 were established with early response to treatment between W0 and W14.

 
Reference
1. Sands BE, et al. N Engl J Med.2019;381:1215-1226.


Table. Clinical Efficacy Outcomes and Disease Control at Weeks 14 and 52 by Anti-TNF Status With Adalimumab and Vedolizumab Treatment in Patients With UC


Figure. Changes in Clinical Efficacy Outcomes and Disease Control From Week 14 to Week 52 by Anti-TNF Status (Naïve/Experienced) With Adalimumab (N=305/N=81) and Vedolizumab (N=304/N=79) Treatment in Patients With UC

Disclosures:
Edward Loftus: AbbVie – Consultant, Grant/Research Support. Allergan – Consultant. Amgen – Consultant, Grant/Research Support. Boehringer Ingelheim – Consultant. Bristol-Myers Squibb – Consultant, Grant/Research Support. Celgene – Consultant, Grant/Research Support. Celltrion – Consultant. Eli Lilly – Consultant. Genentech – Consultant, Grant/Research Support. Gilead – Consultant, Grant/Research Support. Janssen – Consultant, Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Receptos – Grant/Research Support. Robarts Clinical Trials – Grant/Research Support. Takeda – Consultant, Grant/Research Support. UCB – Consultant, Grant/Research Support.
Silvio Danese: AbbVie – Consultant, Other Financial or Material Support, Lecture Fees. Allergan – Consultant, Other Financial or Material Support, Lecture Fees. Biogen – Consultant, Other Financial or Material Support, Lecture Fees. Boehringer Ingelheim – Consultant, Other Financial or Material Support, Lecture Fees. Celgene – Consultant, Other Financial or Material Support, Lecture Fees. Celltrion – Consultant, Other Financial or Material Support, Lecture Fees. Ferring – Consultant, Other Financial or Material Support, Lecture Fees. Hospira – Consultant, Other Financial or Material Support, Lecture Fees. Johnson and Johnson – Consultant, Other Financial or Material Support, Lecture Fees. Merck – Consultant, Other Financial or Material Support, Lecture Fees. MSD – Consultant, Other Financial or Material Support, Lecture Fees. Mundipharma – Consultant, Other Financial or Material Support, Lecture Fees. Pfizer – Consultant, Other Financial or Material Support, Lecture Fees. Sandoz – Consultant, Other Financial or Material Support, Lecture Fees. Takeda – Consultant, Other Financial or Material Support, Lecture Fees. Tigenix – Consultant, Other Financial or Material Support, Lecture Fees. UCB Pharma – Consultant, Other Financial or Material Support, Lecture Fees. Vifor – Consultant, Other Financial or Material Support, Lecture Fees.
Laurent Peyrin-Biroulet: AbbVie – Grant/Research Support, Other Financial or Material Support, Personal Fees. Allergan – Other Financial or Material Support, Personal Fees. Alma – Other Financial or Material Support, Personal Fees. Amgen – Other Financial or Material Support, Personal Fees. Applied Molecular Transport – Other Financial or Material Support, Personal Fees. Arena – Other Financial or Material Support, Personal Fees. Biogen – Other Financial or Material Support, Personal Fees. BMS – Other Financial or Material Support, Personal Fees. Boehringer Ingelheim – Other Financial or Material Support, Personal Fees. Celgene – Other Financial or Material Support, Personal Fees. Celltrion – Other Financial or Material Support, Personal Fees. CTMA – Stockholder/Ownership Interest (excluding diversified mutual funds). Eli Lilly – Other Financial or Material Support, Personal Fees. Enterome – Other Financial or Material Support, Personal Fees. Enthera – Other Financial or Material Support, Personal Fees. Ferring – Other Financial or Material Support, Personal Fees. Fresenius Kabi – Other Financial or Material Support, Personal Fees. Genentech – Other Financial or Material Support, Personal Fees. Genentech – Other Financial or Material Support, Personal Fees. Gilead – Other Financial or Material Support, Personal Fees. Hikma – Other Financial or Material Support, Personal Fees. Index Pharmaceuticals – Other Financial or Material Support, Personal Fees. Janssen – Other Financial or Material Support, Personal Fees. MSD – Grant/Research Support, Other Financial or Material Support, Personal Fees. Mylan – Other Financial or Material Support, Personal Fees. Nestle – Other Financial or Material Support, Personal Fees. Norgine – Other Financial or Material Support, Personal Fees. Oppilan Pharma – Other Financial or Material Support, Personal Fees. OSE Immunotherapeutics – Other Financial or Material Support, Personal Fees. Pfizer – Other Financial or Material Support, Personal Fees. Pharmacosmos – Other Financial or Material Support, Personal Fees. Roche – Other Financial or Material Support, Personal Fees. Samsung Bioepis – Other Financial or Material Support, Personal Fees. Sandoz – Other Financial or Material Support, Personal Fees. Sterna – Other Financial or Material Support, Personal Fees. Sublimity Therapeutics – Other Financial or Material Support, Personal Fees. Takeda – Grant/Research Support, Other Financial or Material Support, Personal Fees. Theravance – Other Financial or Material Support, Personal Fees. Tillots – Other Financial or Material Support, Personal Fees. Vifor – Other Financial or Material Support, Personal Fees.
Jean-Frederic Colombel: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, Lecture Fees. Amgen – Advisory Committee/Board Member, Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Celgene Corporation – Advisory Committee/Board Member, Consultant. Celltrion – Advisory Committee/Board Member, Consultant. Enterome – Advisory Committee/Board Member, Consultant. Ferring – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, Lecture Fees. Genentech – Advisory Committee/Board Member, Consultant, Grant/Research Support. Genfit – Stockholder/Ownership Interest (excluding diversified mutual funds). Intestinal Biotech Development – Stockholder/Ownership Interest (excluding diversified mutual funds). Janssen – Advisory Committee/Board Member, Consultant. Medimmune – Advisory Committee/Board Member, Consultant. Merck – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Protagonist – Advisory Committee/Board Member, Consultant. Second Genome – Advisory Committee/Board Member, Consultant. Seres – Advisory Committee/Board Member, Consultant. Shire – Other Financial or Material Support, Lecture Fees. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, Lecture Fees. Theradiag – Advisory Committee/Board Member, Consultant.
Bruce Sands: 4D Pharma – Consultant. AbbVie – Consultant. Allergan – Consultant. Amgen – Consultant. Arena Pharmaceuticals – Consultant. AstraZeneca – Consultant. Boehringer Ingelheim – Consultant. Capella Biosciences – Consultant. Celgene – Consultant. Celltrion – Consultant. Eli Lilly – Consultant. EnGene – Consultant. F. Hoffmann-La Roche – Consultant. Ferring – Consultant. Gilead – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Consultant, Grant/Research Support. Lyndra – Consultant. Medimmune – Consultant. Oppilan Pharma – Consultant. Otsuka America Pharmaceutical – Consultant. Palatin Technologies – Consultant. Pfizer – Consultant, Grant/Research Support. Progenity – Consultant. Prometheus Laboratories – Consultant. Protagonist – Consultant. Rheos Medicines – Consultant. Seres – Consultant. Shire – Consultant. Sienna Biopharmaceuticals – Consultant. Synergy Pharmaceuticals – Consultant. Takeda – Consultant, Grant/Research Support. Target PharmaSolutions – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. Tigenix – Consultant. UCB – Consultant. Valeant Pharmaceuticals North America – Consultant. Vivelix Pharmaceuticals – Consultant.
Dirk Lindner: Takeda – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Richard Lirio: Takeda – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Christian Agboton: Takeda – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Stefan Schreiber: AbbVie – Consultant. Celltrion – Consultant. Janssen – Consultant. Merck – Consultant. Pfizer – Consultant. Roche – Consultant. Takeda – Consultant.