P497. Efficacy of continued vedolizumab therapy in patients with Crohn's disease who did not respond to vedolizumab induction therapy at week 6
W.J. Sandborn1, B. Feagan2, W. Reinisch3,4, M. Smyth5, J. Xu6, A. Parikh7, I. Fox8, 1University of California San Diego, Division of Gastroenterology, La Jolla, United States, 2Western University/Robarts Research Institute, Robarts Clinical Trials Inc., London, Canada, 3Medical University of Vienna, Internal Medicine/Gastroenterology, Vienna, Austria, 4McMaster University, Audrey Campbell Chair in Ulcerative Colitis, Hamilton, Canada, 5Takeda Development Centre (Europe) Ltd, General Medicine/GI/Renal, London, United Kingdom, 6Takeda Pharmaceuticals International Company, Biostatistics, Cambridge, United States, 7Takeda Pharmaceuticals International, Inc., General Medicine, Deerfield, United States, 8Takeda Pharmaceuticals International Company, Clinical Development, Cambridge, United States
Vedolizumab (VDZ) was evaluated in the phase 3 GEMINI 2 study in patients with Crohn's disease (CD); ∼50% of these patients had a week 6 clinical response to VDZ induction therapy. The current analysis evaluated the effects of continued VDZ therapy on remission and Crohn's Disease Activity Index (CDAI)-100 response rates in week 6 VDZ nonresponders in GEMINI 2.
Patients with CD in GEMINI 2 were randomised to receive placebo (PBO) or VDZ 300 mg (cohort 1) or received open-label VDZ (cohort 2) intravenously at weeks 0 and 2 in the 6-week induction trial; week 6 clinical response (≥70-point decrease in CDAI score from baseline) was assessed. For the 46-week maintenance trial, week 6 VDZ nonresponders were assigned to receive VDZ every 4 weeks (Q4W), and PBO patients continued to receive PBO; week 6 PBO nonresponders were the comparators in this analysis. At weeks 10 and 14 (prespecified) and week 52 (post hoc), proportions of week 6 nonresponders in clinical remission (CDAI score ≤150 points) and of those with a CDAI-100 response (≥100-point decrease in CDAI score from baseline) were assessed, as were week 52 end points for those with a delayed response at week 10 or 14.
Mean CD durations (VDZ, 9.2 years; PBO, 8.2 years) and CDAI scores (VDZ, 323.4; PBO, 324.6) were similar for the VDZ (cohorts 1 and 2; n = 967) and PBO (cohort 1; n = 148) groups at baseline; tumor necrosis factor antagonists had failed in 59% of VDZ and 47% of PBO patients. Proportions of week 6 nonresponders in clinical remission or with a CDAI-100 response at week 10, 14, or 52 were generally numerically higher with VDZ than with PBO (Table). For both end points, the between-treatment group differences generally increased over time and were more pronounced for CDAI-100 response than for remission. Proportions of week 6 nonresponders with remission (41.3%) or a CDAI-100 response (54.5%) at week 52 were higher in week 14 delayed VDZ responders (n = 121) than proportions (33.3% and 43.8%, respectively) in week 10 delayed VDZ responders (n = 96). Among PBO-treated patients, proportions of patients with remission or a CDAI-100 response were 16.7% and 25%, respectively, at week 52 in week 14 responders (n = 12), while the proportions were 16.7% and 16.7%, respectively in week 10 responders (n = 6); however, subgroup sizes were small.
|End points in Wk 6 Nonresponders a||VDZ combined (Induction cohorts 1 and 2)|
n = 351
|PBO (Induction cohort 1)|
n = 69
|Wk 10 b||Wk 14 b||Wk 52 c||Wk 10 b||Wk 14 b||Wk 52 c|
|95% CI||(4.2, 9.5)||(7.3, 13.8)||(14.7, 22.9)||(0, 9.2)||(3.0, 17.3)||(1.1, 13.4)|
|95% CI||(12.1, 19.8)||(17.3, 26.0)||(20.8, 29.9)||(3.0, 17.3)||(4.0, 19.1)||(1.1, 13.4)|
|a Data are % of patients. PBO, placebo; VDZ, vedolizumab.|
b Prespecified analysis. c Post hoc analysis.
In week 6 induction nonresponders with CD, continued VDZ led to additional effects on clinical remission and CDAI-100 response rates at weeks 10, 14, and 52.