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

Edward V Loftus Jr, Bruce E Sands, Jean-Frédéric Colombel, Iris Dotan, Javaria Mona Khalid, David Tudor, Parnia Geransar, Edward V Loftus Jr, Bruce E Sands, Jean-Frédéric Colombel, Iris Dotan, Javaria Mona Khalid, David Tudor, Parnia Geransar

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.

Conflict of interest statement

EVL has received financial support for research from: AbbVie, Takeda, Janssen, UCB, Amgen, Pfizer, Genentech, Celgene, Receptos, Gilead, MedImmune, Seres Therapeutics, and Robarts Clinical Trials; and has served as a consultant for AbbVie, Takeda, Janssen, UCB, Amgen, Pfizer, Eli Lilly, Celltrion Healthcare, Allergan, Bristol-Myers Squibb, Gilead, Genentech, Celgene, and Boehringer Ingelheim. BES has received financial support for research from: Takeda, Janssen, Theravance Biopharma, Pfizer; and has served as a consultant for: 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Capella Bioscience, Celgene, Celltrion Healthcare, Eli Lilly and Company, EnGene, F. Hoffmann-La Roche, Ferring, Gilead Sciences, Ironwood Pharmaceuticals, Janssen, Lyndra, MedImmune, Oppilan Pharma, Otsuka America Pharmaceutical, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, Protagonist Therapeutics, Rheos Medicines, Seres Therapeutics, Shire, Sienna Biopharmaceuticals, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma, TiGenix, UCB, Valeant Pharmaceuticals North America, Vivelix Pharmaceuticals. J-FC has served as a consultant/advisory board member for: AbbVie, Amgen, Arena Pharmaceuticals, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Geneva Pharmaceuticals, Genentech, Janssen Pharmaceuticals, Immunic, Ipsen, Landos, Medimmune, Merck & Co., Novartis, O Mass, Otsuka, Pfizer, Takeda, Tigenix, and Viela Bio; has served as a speaker for: AbbVie, Allergan, Amgen, Ferring Pharmaceuticals, and Takeda; has received research support from: AbbVie, Janssen Pharmaceuticals, and Takeda; and has stock options in: Intestinal Biotech Development and Genfit. ID has served as a consultant/advisory board member for: Pfizer, AbbVie, Janssen, Takeda, Genentech, Neopharm, Celltrion, Celgene, Arena, Gilead, Medtronic/given imaging, Rafa Laboratories; has served as a speaker for: Takeda, AbbVie, Janssen, Genentech, Pfizer, Ferring, Falk Pharma, Celltrion; has received research support from: Pfizer, AbbVie. JMK was an employee of Takeda International - UK Branch at the time this study was conducted. DT was a biostatistics consultant on temporary contract at Takeda Pharmaceuticals AG at the time this study was conducted. PG is an employee of Takeda Pharmaceuticals International AG and holds Takeda stock or stock options. The authors report no other conflicts of interest in this work.

© 2020 Loftus Jr et al.

Figures

Figure 1
Figure 1
Sustained CS-free clinical remissiona (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
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
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).

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