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11. Vedolizumab induction therapy for patients with Crohn's disease and prior anti-tumour necrosis factor antagonist failure: a randomised, placebo-controlled, double-blind, multicentre trial

B. Sands1, B. Feagan2, P. Rutgeerts3, J.-F. Colombel4, W. Sandborn5, R. Sy6, G. D'Haens7, S. Ben-Horin8, J. Xu9, I. Fox9, A. Parikh10, C. Milch9, S. Hanauer11, 1Mount Sinai School of Medicine, Division of Gastroenterology, New York, United States, 2Robarts Research Institute, University of Western Ontario, London, Canada, 3University of Leuven, Leuven, Belgium, 4Hôpital Huriez, Department of Hepatogastroenterology, Lille, France, 5University of California, San Diego Health System, San Diego, United States, 6University of Ottawa, Division of Gastroenterology, Department of Medicine, Ottawa, Canada, 7University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands, 8Chaim Sheba Medical Center, Department of Gastroenterology, Tel-Aviv, Israel, 9Millennium Pharmaceuticals, Inc., Cambridge, United States, 10Takeda Pharmaceuticals, Inc., Chicago, United States, 11University of Chicago Medical Center, Section of Gastroenterology, Hepatology and Nutrition, Chicago, United States

Background

The primary analysis of the efficacy and safety of vedolizumab (VDZ) as induction therapy in Crohn's disease (CD) was conducted in patients (pts) with prior anti-tumour necrosis factor (TNF) failure (GEMINI III; NCT01224171).

Methods

In a phase 3 study, pts with moderately to severely active CD (CD Activity Index [CDAI] 220–400) and failure or intolerance to prior therapy were randomised 1:1 to receive intravenous VDZ 300 mg or placebo (PBO) at wks 0, 2, and 6. The primary endpoint was clinical remission (CDAI ≤150) at wk 6 in pts with prior anti-TNF failure. Secondary endpoints included clinical remission at wk 6 in the overall population, clinical remission at wk 10 in anti-TNF failure and overall populations, sustained clinical remission (CDAI ≤150 at weeks 6 and 10) in both populations, and CDAI 100 response (≥100-point decrease from baseline in CDAI) in the anti-TNF failure population. Endpoints were tested sequentially; Hochberg method was used to control alpha.

Results

Baseline CDAI was slightly higher in the VDZ than the PBO group (313.9 vs 301.3; P = 0.015); pt characteristics were otherwise similar. In the anti-TNF failure population, clinical remission rates at wk 6 were not statistically significant between VDZ and PBO groups; thus, key secondary endpoint analyses are exploratory.

Greater proportions of VDZ-treated pts had CDAI 100 response at wk 6 and were in clinical remission by wk 10 vs PBO in the anti-TNF failure and in the overall populations. In the overall population, more pts in the VDZ group had sustained clinical remission vs PBO. Treatment-emergent AEs were reported in 56% of VDZ pts vs 60% of PBO pts; serious AEs were reported in 6% vs 8%, respectively, with no deaths.

Table: Efficacy outcomes
 Anti-TNF failure populationOverall population
 PBO (n = 157)VDZ (n = 158)PBO (n = 207)VDZ (n = 209)
Primary Endpoint
Pts with clinical remission at wk 6, %12.115.2  
P value   0.4332 
Exploratory Analyses
Pts with clinical remission at wk 6, %  12.119.1
P value     0.0478
Pts with clinical remission at wk 10, %12.126.613.028.7
P value   0.0012   <0.0001
Pts with sustained remission, %8.312.08.215.3
P value   0.2755   0.0249
Pts with CDAI 100 response at wk 6, %22.339.222.739.2
P value   0.0011   0.0002
Pts with CDAI 100 response at wk 10, %24.846.824.247.8
P value   <0.0001   <0.0001

Conclusion

In the anti-TNF failure population, clinical remission rates at wk 6 were not higher with VDZ vs PBO. However, CDAI 100 response at wk 6 and clinical remission at wk 10 were higher in the VDZ group, suggesting that remission may be achieved beyond the 6-wk period of treatment and evaluation used for the primary analysis in this study. VDZ therapy had beneficial effects in the anti-TNF failure and overall populations vs PBO.