Sustained Clinical Remission With Vedolizumab in Patients With Moderate-to-Severe Ulcerative Colitis

Abstract

Background: Sustaining clinical remission is an important treatment goal in moderate-to-severe UC. This post hoc exploratory analysis assessed the long-term efficacy of vedolizumab in the subset of patients with UC in the GEMINI 1 study who were in clinical remission by week 14 after 3 induction doses, administered at weeks 0, 2, and 6.

Methods: Sustained clinical remission (primary endpoint) was evaluated using 2 definitions: (1) a partial Mayo Score (pMS) of ≤2 with no subscore >1 and (2) a rectal bleeding subscore (RBS) of 0 throughout weeks 14, 26, 38, and 52.

Results: The proportion of patients in clinical remission at week 14 was significantly higher in patients receiving vedolizumab (n = 620) compared with placebo (n = 149) (pMS: 32.7% vs 20.1% [percentage-point difference (∆) 12.6%; 95% confidence interval [CI], 5.2-20.0]; RBS: 47.3% vs 28.9% [∆18.4%; 95% CI, 10.1-26.7]). Of patients in clinical remission at week 14, a significantly higher proportion of vedolizumab-treated patients achieved sustained clinical remission compared with placebo (pMS: 66.5% vs 26.7%; ∆39.8%; 95% CI, 22.7-56.9; RBS: 56.7% vs 20.9%; ∆35.7%; 95% CI, 22.3-49.1). Findings were consistent in tumor necrosis factor (TNF) antagonist-naive and antagonist-failure patients.

Conclusion: Compared with placebo, 35%-40% more patients receiving a full induction course of vedolizumab had sustained clinical remission after 52 weeks of therapy. This result was observed irrespective of TNF antagonist treatment history. Clinical remission at week 14 may therefore be a predictor for sustained clinical remission with vedolizumab.

Trial registration: ClinicalTrials.gov NCT00783718 NCT00790933.

Keywords: TNF antagonist; remission; ulcerative colitis; vedolizumab.

FIGURE 1.

Design of GEMINI 1 and patient disposition. GEMINI 1 study design and disposition of patients with moderate-to-severe UC failing conventional therapy. Cohort 1, randomized to double-blind vedolizumab or placebo at weeks 0 and 2; cohort 2 (required to ensure sufficient sample size in maintenance phase) received open-label vedolizumab at weeks 0 and 2. The 2 cohorts were integrated for the maintenance phase (up to week 52) based on clinical response* at week 6. Vedolizumab nonresponders received open-label vedolizumab Q4W, while responders were re-randomized to double-blind vedolizumab Q4W, Q8W, or placebo. Patients discontinuing vedolizumab induction (cohort 1: n = 7; cohort 2: n = 36) or placebo (n = 14) were re-assigned to open-label vedolizumab Q4W maintenance (nonresponder) or to the placebo group, respectively (stippled arrows). *Reduction from baseline in total MS of ≥3 points and ≥30% decrease from baseline, with ≥1-point decrease in RBS or an absolute ≤1-point RBS. ^†Sustained clinical remission (weeks 14, 26, 38, and 52) assessed according to 2 definitions: (1) pMS ≤2 points and no individual subscore >1 point, and (2) RBS of 0. Data substitution from GEMINI LTS was performed for 3.4% (n = 21), 16.3% (n = 101), 18.2% (n = 113), and 16.1% (n = 100) of the combined VDZ group at weeks 14, 26, 38, and 52, respectively. Abbreviations: DB, double-blind; OL, open-label.

FIGURE 2.

Sustained clinical remission based on (A) pMS (≤2 points and no individual subscore >1 point) or (B) RBS of 0 at weeks 14, 26, 38, and 52. Data substitution from the GEMINI LTS study was performed for 3.4% (n = 21), 16.3% (n = 101), 18.2% (n = 113), and 16.1% (n = 100) of the combined VDZ group at weeks 14, 26, 38, and 52, respectively. The n value in each bar indicates patients who were in clinical remission at week 14. *Indicates significance based on the 95% CI for percentage-point difference between combined VDZ and PLA groups.