P0588 Efficacy and health-related quality of life associated with second-line vedolizumab after one prior first-line anti-tumour necrosis factor treatment in patients with active ulcerative colitis: A meta-analysis of the GEMINI-1 and VISIBLE-1 trials
Authors: Atreya R , Kirchgesner J , Cheah Z , Biedermann P , Bakker L , Meyer M , Raine T 
Published: January 2025

Abstract

Background
Vedolizumab (VDZ) is a monoclonal antibody approved for adults with moderately to severely active ulcerative colitis (UC) and an inadequate response/intolerance to conventional therapy or anti-tumour necrosis factor (TNF) treatment. There is published evidence supporting the use of VDZ as a first-line biologic in patients with UC, but additional efficacy data for second-line VDZ (after first-line anti-TNF treatment) are required to define its optimal position in the treatment sequence. We conducted a meta-analysis of the efficacy and health-related quality of life (HRQoL) associated with second-line VDZ treatment exposure in patients with UC using data from the randomized, placebo (PBO)-controlled phase 3 GEMINI-1/VISIBLE-1 trials.

Methods
GEMINI-1 (NCT00783718) evaluated intravenous (IV) VDZ as induction/maintenance treatment in patients with active UC.1 VISIBLE-1 (NCT02611830) assessed IV/subcutaneous maintenance VDZ in patients with moderately/severely active UC.2 Patients who received first-line anti-TNF treatment within 5 years before trial enrolment were included in the meta-analysis. The primary outcome was clinical remission (defined as Adapted Mayo Score [AMS] 1 or 2; Figure). Secondary outcomes included corticosteroid-free remission, mucosal healing and HRQoL (measured via the Inflammatory Bowel Disease Questionnaire and EuroQoL-5 Dimension Visual Analogue Scale). Outcomes were assessed at Week 52. Study-specific treatment effects were estimated using generalized linear models. Efficacy of VDZ vs PBO was compared using fixed-effects models. Regression analyses assessed treatment effects, adjusting for disease location/duration and previous corticosteroid use.

Results
In total, 137 patients from GEMINI-1/VISIBLE-1 were included (VDZ, n=89; PBO, n=48). Patient characteristics were similar across cohorts, but the mean (standard deviation) disease duration ranged from 6.6 (4.4) years (GEMINI-1 VDZ IV cohort) to 9.9 (10.1) years (VISIBLE-1 PBO cohort). Second-line VDZ was associated with a higher likelihood of achieving clinical remission (AMS 1 and 2; Figure) and all secondary outcomes, including improved HRQoL, at Week 52 vs PBO (Table). Regression analysis showed that patients treated with VDZ were 11.35 (95% confidence interval 3.25–39.63) times more likely to achieve clinical remission (defined as AMS 1) vs PBO.

Conclusion
Second-line VDZ after first-line anti-TNF treatment significantly increased the likelihood of achieving clinical remission, mucosal healing and improved HRQoL at Week 52 vs PBO in patients with UC. The small sample size and heterogeneity observed in some outcomes warrant further research to strengthen these findings.

References
1. Feagan BG et al. N Engl J Med 2013;369:699-710.
2. Sandborn WJ et al. Gastroenterology 2020;158:562-572 e12.
3. Sandborn W. J. et al. Crohns Colitis 360 2023;6:otad076.