Laurent Peyrin-Biroulet1, Edward V Loftus2, Jean-Frédéric Colombel3, Silvio Danese4, Raquel Rogers5, Jeffrey D Bornstein5, Jingjing Chen5, Stefan Schreiber6, Bruce E Sands3, Richard A Lirio5. 1. Department of Gastroenterology, Nancy University Hospital, and INSERM U1256 Nutrition-Genetics and Environmental Risk Exposure, Lorraine University, Vandoeuvre-lès-Nancy, France. Electronic address: peyrinbiroulet@gmail.com. 2. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota. 3. Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. 4. Department of Biomedical Sciences, Humanitas Clinical and Research Center-Istituto di Ricovero e Cura a Carattere Scientifico, Humanitas University, Milan, Italy. 5. Takeda Development Center Americas Inc, Cambridge, Massachusetts. 6. Department of Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
Abstract
BACKGROUND AND AIMS: VARSITY (An Efficacy and Safety Study of Vedolizumab Intravenous [IV] Compared to Adalimumab Subcutaneous [SC] in Participants With Ulcerative Colitis) showed superior clinical remission and endoscopic improvement in ulcerative colitis with vedolizumab vs adalimumab. This analysis compared histologic outcomes. METHODS: Patients in VARSITY were randomized 1:1 to maintenance with vedolizumab IV 300 mg every 8 weeks or adalimumab SC 40 mg every 2 weeks (both following standard induction). Geboes Index and Robarts Histopathology Index (RHI) scores were used to assess prespecified histologic exploratory end points of histologic remission (Geboes <2 or RHI ≤2) and minimal histologic disease activity (Geboes ≤3.1 or RHI ≤4) at weeks 14 and 52. RESULTS: In total, 769 patients received vedolizumab (n = 383) or adalimumab (n = 386). Mean baseline histologic disease activity was similar between vedolizumab and adalimumab groups. Vedolizumab induced greater histologic remission than adalimumab at week 14 (Geboes: 16.7% vs 7.3%, Δ9.4% [95% confidence interval {CI}, 4.9%-13.9%], P < .0001; RHI: 25.6% vs 16.1%, Δ9.5% [95% CI, 3.8%-15.2%], P = .0011) and week 52 (Geboes: 29.2% vs 8.3%, Δ20.9% [95% CI, 15.6%-26.2%], P < .0001; RHI: 37.6% vs 19.9%, Δ17.6% [95% CI, 11.3%-23.8%], P < .0001) overall and in both anti-tumor necrosis factor (TNF)-naïve and -failure subgroups. Results were similar for minimal histologic disease activity. Histologic outcomes were generally better in anti-TNF-naïve vs -failure patients. At week 52, rates of mucosal healing (composite end point of histologic plus endoscopic improvement) were also higher with vedolizumab than adalimumab (Geboes: 25.6% vs 6.7%; RHI: 30.5% vs 14.5%). CONCLUSIONS: Higher rates of histologic remission, minimal histologic disease activity, and combined histologic plus endoscopic outcomes were observed with vedolizumab than with adalimumab in ulcerative colitis in both anti-TNF-naïve and -failure subgroups. REGISTRATION: ClinicalTrials.gov NCT02497469; EudraCT 2015-000939-33.
BACKGROUND AND AIMS: VARSITY (An Efficacy and Safety Study of Vedolizumab Intravenous [IV] Compared to Adalimumab Subcutaneous [SC] in Participants With Ulcerative Colitis) showed superior clinical remission and endoscopic improvement in ulcerative colitis with vedolizumab vs adalimumab. This analysis compared histologic outcomes. METHODS: Patients in VARSITY were randomized 1:1 to maintenance with vedolizumab IV 300 mg every 8 weeks or adalimumab SC 40 mg every 2 weeks (both following standard induction). Geboes Index and Robarts Histopathology Index (RHI) scores were used to assess prespecified histologic exploratory end points of histologic remission (Geboes <2 or RHI ≤2) and minimal histologic disease activity (Geboes ≤3.1 or RHI ≤4) at weeks 14 and 52. RESULTS: In total, 769 patients received vedolizumab (n = 383) or adalimumab (n = 386). Mean baseline histologic disease activity was similar between vedolizumab and adalimumab groups. Vedolizumab induced greater histologic remission than adalimumab at week 14 (Geboes: 16.7% vs 7.3%, Δ9.4% [95% confidence interval {CI}, 4.9%-13.9%], P < .0001; RHI: 25.6% vs 16.1%, Δ9.5% [95% CI, 3.8%-15.2%], P = .0011) and week 52 (Geboes: 29.2% vs 8.3%, Δ20.9% [95% CI, 15.6%-26.2%], P < .0001; RHI: 37.6% vs 19.9%, Δ17.6% [95% CI, 11.3%-23.8%], P < .0001) overall and in both anti-tumor necrosis factor (TNF)-naïve and -failure subgroups. Results were similar for minimal histologic disease activity. Histologic outcomes were generally better in anti-TNF-naïve vs -failure patients. At week 52, rates of mucosal healing (composite end point of histologic plus endoscopic improvement) were also higher with vedolizumab than adalimumab (Geboes: 25.6% vs 6.7%; RHI: 30.5% vs 14.5%). CONCLUSIONS: Higher rates of histologic remission, minimal histologic disease activity, and combined histologic plus endoscopic outcomes were observed with vedolizumab than with adalimumab in ulcerative colitis in both anti-TNF-naïve and -failure subgroups. REGISTRATION: ClinicalTrials.gov NCT02497469; EudraCT 2015-000939-33.
Authors: Olga Maria Nardone; Alina Bazarova; Pradeep Bhandari; Rosanna Cannatelli; Marco Daperno; Jose Ferraz; Martin Goetz; Xianyong Gui; Bu Hayee; Gert De Hertogh; Mark Lazarev; Ji Li; Adolfo Parra-Blanco; Luca Pastorelli; Remo Panaccione; Vincenzo Occhipinti; Timo Rath; Samuel C L Smith; Uday N Shivaji; Gian Eugenio Tontini; Michael Vieth; Vincenzo Villanacci; Davide Zardo; Raf Bisschops; Ralf Kiesslich; Subrata Ghosh; Marietta Iacucci Journal: United European Gastroenterol J Date: 2022-02-23 Impact factor: 4.623