Efficacy of vedolizumab in fistulising Crohn's disease: Exploratory analyses of data from GEMINI 2

Brian G. Feagan, David Schwartz, Silvio Danese, David T. Rubin, Trevor W. Lissoos, Jing Xu, Karen Lasch

Research output: Contribution to journalArticle

Abstract

Background and Aims: Medical management of fistulising Crohn's disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4β7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692]. Methods: Exploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates. Results: At entry into the maintenance period, 153 [33%] patients had a history of fistulising disease and 57 [12%] patients had ≥1 active draining fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO-treated patients (95% confidence interval [CI], -11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction [ARR]: 19.7%; 95% CI, -8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54-11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059-0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates. Conclusions: Our findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.

Original languageEnglish
Pages (from-to)621-626
Number of pages6
JournalJournal of Crohn's and Colitis
Volume12
Issue number5
DOIs
Publication statusPublished - Apr 27 2018

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Crohn Disease
Fistula
Confidence Intervals
Maintenance
Numbers Needed To Treat
Therapeutics
vedolizumab
Proportional Hazards Models
Integrins
Placebos
Anti-Bacterial Agents

Keywords

  • Crohn's disease
  • Fistula
  • Vedolizumab

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Efficacy of vedolizumab in fistulising Crohn's disease : Exploratory analyses of data from GEMINI 2. / Feagan, Brian G.; Schwartz, David; Danese, Silvio; Rubin, David T.; Lissoos, Trevor W.; Xu, Jing; Lasch, Karen.

In: Journal of Crohn's and Colitis, Vol. 12, No. 5, 27.04.2018, p. 621-626.

Research output: Contribution to journalArticle

Feagan, Brian G. ; Schwartz, David ; Danese, Silvio ; Rubin, David T. ; Lissoos, Trevor W. ; Xu, Jing ; Lasch, Karen. / Efficacy of vedolizumab in fistulising Crohn's disease : Exploratory analyses of data from GEMINI 2. In: Journal of Crohn's and Colitis. 2018 ; Vol. 12, No. 5. pp. 621-626.
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abstract = "Background and Aims: Medical management of fistulising Crohn's disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4β7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692]. Methods: Exploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates. Results: At entry into the maintenance period, 153 [33{\%}] patients had a history of fistulising disease and 57 [12{\%}] patients had ≥1 active draining fistula. By Week 14, 28{\%} of VDZ/VDZ-treated patients compared with 11{\%} of VDZ/PBO-treated patients (95{\%} confidence interval [CI], -11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31{\%} and 11{\%} (absolute risk reduction [ARR]: 19.7{\%}; 95{\%} CI, -8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33{\%} vs 11{\%}; HR: 2.54; 95{\%} CI, 0.54-11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95{\%} CI, 0.059-0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates. Conclusions: Our findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.",
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T2 - Exploratory analyses of data from GEMINI 2

AU - Feagan, Brian G.

AU - Schwartz, David

AU - Danese, Silvio

AU - Rubin, David T.

AU - Lissoos, Trevor W.

AU - Xu, Jing

AU - Lasch, Karen

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N2 - Background and Aims: Medical management of fistulising Crohn's disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4β7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692]. Methods: Exploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates. Results: At entry into the maintenance period, 153 [33%] patients had a history of fistulising disease and 57 [12%] patients had ≥1 active draining fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO-treated patients (95% confidence interval [CI], -11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction [ARR]: 19.7%; 95% CI, -8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54-11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059-0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates. Conclusions: Our findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.

AB - Background and Aims: Medical management of fistulising Crohn's disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4β7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692]. Methods: Exploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates. Results: At entry into the maintenance period, 153 [33%] patients had a history of fistulising disease and 57 [12%] patients had ≥1 active draining fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO-treated patients (95% confidence interval [CI], -11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction [ARR]: 19.7%; 95% CI, -8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54-11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059-0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates. Conclusions: Our findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.

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