TY - JOUR
T1 - Histologic Outcomes With Vedolizumab Versus Adalimumab in Ulcerative Colitis
T2 - Results From An Efficacy and Safety Study of Vedolizumab Intravenous Compared to Adalimumab Subcutaneous in Participants With Ulcerative Colitis (VARSITY)
AU - Peyrin-Biroulet, Laurent
AU - Loftus, Edward V.
AU - Colombel, Jean Frédéric
AU - Danese, Silvio
AU - Rogers, Raquel
AU - Bornstein, Jeffrey D.
AU - Chen, Jingjing
AU - Schreiber, Stefan
AU - Sands, Bruce E.
AU - Lirio, Richard A.
N1 - Funding Information:
Conflicts of interest These authors disclose the following: Laurent Peyrin-Biroulet discloses personal fees from AbbVie, Janssen, Genentech, Ferring, Tillotts, Pharmacosmos, Celltrion, Takeda, Boehringer Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestl?, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Eli Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Therevance; grants from AbbVie, MSD, and Takeda; and stock options from CTMA. Edward V. Loftus Jr discloses financial support for research from AbbVie, Takeda, Janssen, UCB, Amgen, Pfizer, Genentech, Celgene, Receptos, Gilead, Bristol-Myers Squibb, Robarts Clinical Trials, and Theravance, and consultancy with AbbVie, Takeda, Janssen, UCB, Amgen, Pfizer, Eli Lilly, Celltrion Healthcare, Allergan, Bristol-Myers Squibb, Celgene, Gilead, Genentech, Boehringer Ingelheim, Calibr, Iterative Scopes, Ono Pharma, Sun Pharma, and Arena. Jean-Fr?d?ric Colombel discloses research grants from AbbVie, Janssen Pharmaceuticals, and Takeda; lecture fees from AbbVie, Amgen, Allergan, Inc, Ferring Pharmaceuticals, Shire, and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Geneva, Genentech, Janssen Pharmaceuticals, Immunic, Landos, Ipsen, Medimmune, Merck, Novartis, OMass Therapeutics, Otsuka, Pfizer, Shire, Takeda, Tigenix, and Viela Bio; and stock options from Intestinal Biotech Development and Genfit. Silvio Danese discloses lecture fees from AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, and Boehringer Ingelheim, and consultancy with AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, and Boehringer Ingelheim. Raquel Rogers, and Jingjing Chen, are employees of Takeda and hold Takeda stock or stock options. Jeffrey D. Bornstein and Richard A. Lirio were employees of Takeda at the time of this study and held Takeda stock or stock options. Stefan Schreiber discloses consultancy fees from AbbVie, Celltrion, Janssen, Merck, Pfizer, Roche, and Takeda. Bruce E. Sands discloses consultancy with 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Capella Bioscience, Celgene, Celltrion Healthcare, Eli Lilly and Company, EnGene, F. Hoffmann-La Roche, Ferring, Gilead Sciences, Ironwood Pharmaceuticals, Janssen, Lyndra, MedImmune, Oppilan Pharma, Otsuka America Pharmaceutical, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, Protagonist Therapeutics, Rheos Medicines, Seres Therapeutics, Shire, Sienna Biopharmaceuticals, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance BioPharma, TiGenix, UCB, Valeant Pharmaceuticals North America, and Vivelix Pharmaceuticals, and research support from Takeda, Janssen, Theravance, BioPharma, and Pfizer.
Publisher Copyright:
© 2021 The Authors
PY - 2021/10
Y1 - 2021/10
N2 - 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
AB - 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
KW - Endoscopic Improvement
KW - Histologic Remission
KW - Rapid Onset
UR - http://www.scopus.com/inward/record.url?scp=85111539399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111539399&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2021.06.015
DO - 10.1053/j.gastro.2021.06.015
M3 - Article
C2 - 34144047
AN - SCOPUS:85111539399
SN - 0016-5085
VL - 161
SP - 1156-1167.e3
JO - Gastroenterology
JF - Gastroenterology
IS - 4
ER -