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)

Gastroenterology. 2021 Oct;161(4):1156-1167.e3. doi: 10.1053/j.gastro.2021.06.015. Epub 2021 Jun 16.

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.

Keywords: Endoscopic Improvement; Histologic Remission; Rapid Onset.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adalimumab / administration & dosage*
  • Adalimumab / adverse effects
  • Adult
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / pathology
  • Colon / drug effects*
  • Colon / pathology
  • Colonoscopy
  • Double-Blind Method
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Remission Induction
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / administration & dosage*
  • Tumor Necrosis Factor Inhibitors / adverse effects
  • Wound Healing / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Tumor Necrosis Factor Inhibitors
  • vedolizumab
  • Adalimumab

Associated data

  • ClinicalTrials.gov/NCT02497469