Histologic Outcomes With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From An Efficacy and Safety Study of Vedolizumab Intravenous Compared to Adalimumab Subcutaneous in Participants With Ulcerative Colitis (VARSITY)

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 161; no. 4; pp. 1156 - 1167.e3
• Main Authors: Peyrin-Biroulet, Laurent, Loftus, Edward V., Colombel, Jean-Frédéric, Danese, Silvio, Rogers, Raquel, Bornstein, Jeffrey D., Chen, Jingjing, Schreiber, Stefan, Sands, Bruce E., Lirio, Richard A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2021; Elsevier
• Subjects: Adalimumab; Adalimumab - administration & dosage; Adalimumab - adverse effects; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Colitis, Ulcerative; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Colon; Colon - drug effects; Colon - pathology; Colonoscopy; Double-Blind Method; Endoscopic Improvement; Female; Histologic Remission; Humans; Infusions, Intravenous; Injections, Subcutaneous; Life Sciences; Male; Middle Aged; Rapid Onset; Remission Induction; Severity of Illness Index; Time Factors; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor Inhibitors - administration & dosage; Tumor Necrosis Factor Inhibitors - adverse effects; Wound Healing; Wound Healing - drug effects; SC; SD; RHI; Endoscopic Improvement; CI; Rapid Onset; Histologic Remission; IV; TNF; UC; VARSITY
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2021.06.015

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. 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. 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%). 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. ClinicalTrials.gov NCT02497469; EudraCT 2015-000939-33 [Display omitted] In An Efficacy and Safety Study of Vedolizumab Intravenous (IV) Compared to Adalimumab Subcutaneous (SC) in Participants With Ulcerative Colitis (VARSITY), vedolizumab was superior to adalimumab in restoring normal gut histology in ulcerative colitis, with significant differences in both anti–tumor necrosis factor-naïve and -failure subgroups at weeks 14 and 52.