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P323. Sustained therapeutic benefit of vedolizumab throughout 1 year in ulcerative colitis in GEMINI I, a randomized, placebo-controlled, double-blind, multicenter trial

W. Sandborn1, B. Sands2, P. Rutgeerts3, S. Sankoh4, M. Rosario4, C. Milch4, I. Fox4, 1University of California, San Diego Health System, San Diego, 2Mount Sinai School of Medicine, Division of Gastroenterology, New York, USA, 3University of Leuven, Leuven, Belgium, 4Millennium Pharmaceuticals, Inc., Cambridge, United States

Background

We assessed the effect of vedolizumab (VDZ), an investigational, gut-selective monoclonal antibody targeting α4β7 integrin, over 52 wks in patients (pts) with moderately to severely active ulcerative colitis in whom ≥1 prior therapy had failed (GEMINI I; NCT00783718).

Methods

Eligible adult pts had a Mayo score (MS) ≥6 and endoscopic subscore ≥2 despite prior therapy. After 2 induction doses of VDZ (wk 0 and 2), pts with clinical response (reduction in MS of ≥3 points and ≥30% from baseline, plus decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1 point) to VDZ at wk 6 were randomised 1:1:1 to VDZ 300 mg IV every 4 wk (Q4W) or 8 wk (Q8W) or placebo (PBO) for 46 wks. A post hoc analysis was conducted to evaluate the sustained therapeutic benefit of VDZ. Clinical remission was defined as complete MS (CMS) or partial MS (PMS) ≤2 and no individual subscore >1; clinical response was defined as a reduction in PMS ≥2 points and ≥25% from baseline. Moderate to substantial agreement was found between clinical response and remission endpoints as defined by CMS and PMS at wks 6 and 52. Durable mucosal healing (DMH) was defined as Mayo endoscopic subscore ≤1 at wks 6 and 52. An exploratory analysis of corticosteroid (CS) use was also conducted.

Results

Among pts with a clinical response to VDZ at wk 6 (n = 373), decreases in PMS occurred as early as wk 2 (Fig. 1).

After successful induction, PMS remained lower than baseline in both VDZ groups through wk 52, whereas an increase in PMS was noted starting at wk 22 in the PBO group. Remission rates remained stable in VDZ groups over 52 wks but decreased in the PBO group (Fig. 2). DMH was achieved by 42.6%, 43.2%, and 17.5% of pts in the VDZ Q8W, VDZ Q4W, and PBO groups, respectively (P < 0.0001 for both comparisons). Median CS dose declined over the maintenance phase in both VDZ groups, but rose after wk 26 in the PBO group (Fig. 3).

Figure 1. Mean partial Mayo score by study visit in patients with a clinical response to VDZ at Week 6.

Figure 2. Proportion of patients with clinical remission (by partial Mayo score) among those with a clinical response to VDZ at Week 6.

Figure 3. Median corticosteroid dose.

Conclusion

In pts who responded to VDZ by wk 6, sustained reductions in PMS were observed in VDZ-treated patients over a 1-year period versus PBO. VDZ treatment was associated with stable clinical remission rates and increased rates of durable mucosal healing versus PBO.