Deep Remission With Vedolizumab in Patients With Moderately to Severely Active Ulcerative Colitis: A GEMINI 1 post hoc Analysis

Abstract

Background and aims: This GEMINI 1 post hoc analysis evaluated vedolizumab efficacy for inducing deep remission in patients with ulcerative colitis and correlation between vedolizumab trough concentrations and deep remission rates.

Methods: Week 6 vedolizumab responders were re-randomized to placebo or vedolizumab every 8 or 4 weeks. Deep remission at Week 52 was measured using four different definitions [from most to least stringent]: [1] Mayo Clinic endoscopic score = 0, rectal bleeding score = 0 and decrease or no change from baseline in stool frequency score; [2] endoscopic score ≤1, rectal bleeding score = 0 and stool frequency score = 0; [3] endoscopic score ≤1, rectal bleeding score = 0, decrease or no change from baseline stool frequency score, and total score [endoscopic score + rectal bleeding score + stool frequency score] ≤1; and [4] endoscopic score ≤1, rectal bleeding score = 0 and stool frequency score ≤1. Steady-state trough vedolizumab serum concentrations were evaluated.

Results: At Week 6, 373 vedolizumab responders were re-randomized to maintenance placebo [n = 126] or vedolizumab every 8 [n = 122] or 4 [n = 125] weeks. Significantly more vedolizumab patients achieved deep remission at Week 52 for the most (placebo 8.7%, every 8 weeks 27.0% [p = 0.0001], every 4 weeks 28.0% [p < 0.0001]) and least (placebo 15.9%, every 8 weeks 43.4% [p < 0.0001], every 4 weeks 43.2% [p < 0.0001]) stringent definitions. Patients with higher vedolizumab trough concentration quartiles had higher deep remission rates [all definitions] compared with those with the lowest quartile or who received placebo.

Conclusion: Vedolizumab was associated with significantly higher deep remission rates than placebo at Week 52, regardless of deep remission definition [NCT00783718].

Figures

Figure 1.

Deep remission at Week 52a,b [maintenance ITT population]. One patient randomized to PLA still had active drug concentrations [9 μg/mL] at Week 46 and they were in remission according to all four definitions at Week 52. ES, endoscopic score; ITT, intention to treat; PLA, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks; RBS, rectal bleeding score; SFS, stool frequency score; VDZ, vedolizumab. aPost hoc analyses; ball patients in the maintenance ITT population, including those in the PLA group, had received VDZ at Weeks 0 and 2 and had a clinical response at Week 6; †definition 1: Mayo Clinic ES = 0, RBS = 0 and decrease in SFS or no change from baseline [A]; ‡definition 2: Mayo Clinic ES ≤ 1, RBS = 0 and SFS = 0 [B]; §definition 3: Mayo Clinic ES ≤ 1, RBS = 0, decrease in SFS or no change from baseline, and total score [ES + RBS + SFS] ≤ 1 [C]; ¶definition 4: Mayo Clinic ES ≤ 1, RBS = 0 and SFS ≤ 1 [D].

Figure 2.

Endoscopic appearance in the maintenance phase for patients with UC in the GEMINI 1 trial.a,b ITT, intention to treat; PLA, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks; UC, ulcerative colitis; VDZ, vedolizumab. aPercentages for each timepoint may not add up to 100% due to rounding; ball patients in the maintenance ITT population, including those in the placebo group, had received vedolizumab at Weeks 0 and 2 and had a clinical response at Week 6.

Figure 3.

ES at Week 52 by RBS [A] and SFS [B]. ES, endoscopic score; PLA, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks; RBS, rectal bleeding score; SFS, stool frequency score; VDZ, vedolizumab.

Figure 4.

Rates of deep remission by vedolizumab trough serum steady-state concentration quartiles. ES, endoscopic score; ITT, intention to treat; PLA, placebo; RBS, rectal bleeding score; SFS, stool frequency score; VDZ, vedolizumab. †Definition 1: Mayo Clinic ES = 0, RBS = 0 and decrease in SFS or no change from baseline [A]; ‡definition 2: Mayo Clinic ES ≤ 1, RBS = 0 and SFS = 0 [B]; §definition 3: Mayo Clinic ES ≤ 1, RBS = 0, decrease in SFS or no change from baseline, and total score [ES + RBS + SFS] ≤ 1 [C]; ¶definition 4: Mayo Clinic ES ≤ 1, RBS = 0 and SFS ≤ 1 [D]; ††one patient randomized to PLA still had active drug concentrations [9 μg/mL] at Week 46 and was in remission according to all four definitions at Week 52; ‡‡the maintenance PLA non-ITT population received PLA as induction therapy and was not included in the primary maintenance ITT efficacy analyses.