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.

Clinicaltrials.gov

NCT00783718.

Keywords:

• vedolizumab
• ulcerative colitis
• corticosteroid
• anti-tumor necrosis factor alpha
• clinical remission

Abbreviations

AE, adverse event; anti-TNFα, anti-tumor necrosis factor alpha; BMI, body mass index; CI, confidence interval; CS, corticosteroid; IM, immunomodulator; LTS, long-term safety; PLA, placebo; pMS, partial Mayo score; Q4W, every 4 weeks; Q8W, every 8 weeks; SD, standard deviation; UC, ulcerative colitis; VDZ, vedolizumab.

Data Sharing Statement

The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participant data supporting the results reported in this article, will be made available within three months from initial request, to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.

Acknowledgments

Editorial assistance and medical writing support were provided by Chris Barnes, PhD, of ProEd Communications, Inc.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

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.

Additional information

Funding

This study was sponsored by Takeda. Editorial assistance and medical writing support were funded by Takeda.