Sustained Corticosteroid-Free Clinical Remission During Vedolizumab Maintenance Therapy in Patients with Ulcerative Colitis on Stable Concomitant Corticosteroids During Induction Therapy: A Post Hoc Analysis of GEMINI 1

Abstract

Background: Corticosteroid-free clinical remission is important in ulcerative colitis.

Objective: This GEMINI 1 post hoc analysis evaluated vedolizumab efficacy in achieving sustained corticosteroid-free clinical remission in moderately to severely active ulcerative colitis.

Materials and methods: GEMINI 1 included a 6-week induction period followed by a 46-week maintenance period. Patients received stable corticosteroid dosing at baseline/during induction and tapered dosing during maintenance. Analysis groups included vedolizumab (induction and maintenance); vedolizumab/placebo (vedolizumab induction, placebo maintenance); and placebo (induction and maintenance). The primary endpoint was sustained corticosteroid-free clinical remission (partial Mayo score ≤2, no individual subscore >1, for ≥32 weeks). Multivariate analyses identified covariates associated with the primary endpoint. Safety endpoints included adverse events.

Results: Baseline demographics and concomitant corticosteroid use were similar across groups (n=454). A greater proportion (95% confidence interval) of the vedolizumab group achieved sustained corticosteroid-free clinical remission (10.2% [6.9 to 13.6]) vs the placebo group (1.4% [0.0 to 7.3]; difference 8.9% [-3.8 to 21.4]). Proportions were similar between the vedolizumab/placebo and placebo groups. Covariates associated with sustained corticosteroid-free clinical remission (odds ratio [95% confidence interval]) were treatment (vedolizumab vs placebo: 9.35 [1.25 to 71.43]; p=0.0605), anti-tumor necrosis factor alpha exposure (yes vs no: 0.26 [0.12 to 0.57]; p=0.0008), and disease duration (≤2 vs >2 years: 2.66 [0.99-7.19]; p=0.0531). Adverse events were similar across groups.

Conclusion: A numerically greater proportion of vedolizumab-treated patients with ulcerative colitis achieved sustained corticosteroid-free clinical remission. Vedolizumab treatment, no previous anti-tumor necrosis factor alpha exposure, and shorter disease duration were associated with sustained corticosteroid-free clinical remission.

Clinicaltrialsgov: NCT00783718.

Keywords: anti-tumor necrosis factor alpha; clinical remission; corticosteroid; ulcerative colitis; vedolizumab.

Figure 1

Sustained CS-free clinical remission^a (for at least 32 weeks until Week 52, including long-term safety study). ^aPatients using oral CS at baseline who discontinued CS and were in CS-free clinical remission for ≥32 weeks until Week 52 inclusive; clinical remission was defined as pMS ≤2 and no individual score >1. Abbreviations: Anti-TNFα, anti-tumor necrosis factor alpha; CS, corticosteroid; PLA, placebo; VDZ, vedolizumab; VDZ/PLA, vedolizumab (induction) then placebo (maintenance).

Figure 2

Time to sustained CS-free clinical remission (for at least 32 weeks until Week 52). ^a(A) Overall population. (B) Anti-TNFα-naïve subgroup. (C) Anti-TNFα-failure subgroup. ^aPatients using oral CS at baseline who discontinued CS and were in CS-free clinical remission for ≥32 weeks until Week 52 inclusive; clinical remission was defined as pMS ≤2 and no individual score >1. Abbreviations: Anti-TNFα, anti-tumor necrosis factor alpha; CI, confidence interval; CS, corticosteroid; non-est, not possible to conduct Kaplan-Meier estimate; PLA, placebo; pMS, partial Mayo score; VDZ, vedolizumab; VDZ/PLA, vedolizumab (induction) then placebo (maintenance).

Figure 3

Predictive modeling of factors that may influence the frequency of sustained clinical remission in ulcerative colitis. Logistic regression and Chi-square analyses were performed to identify covariates associated with the primary endpoint. Abbreviations: Anti-TNFα, anti-tumor necrosis factor alpha; CI, confidence interval; PLA, placebo; VDZ, vedolizumab; VDZ/PLA, vedolizumab (induction) then placebo (maintenance).