Vedolizumab Demonstrates Early Symptomatic Improvement in Ulcerative Colitis: A GEMINI 1 Post Hoc Analysis

Abstract

BACKGROUND: Vedolizumab (VDZ) achieves long term clinical remission and mucosal healing in patients (pts) with moderately-to-severely active ulcerative colitis (UC). Relief of rectal bleeding (RB) and stool frequency (SF) remain important treatment goals for pts and key indicators of remission for physicians. We aimed to characterize early symptomatic response with VDZ, specifically evaluating the timing of RB and SF improvement. METHODS: We assessed symptomatic improvement with VDZ through post-hoc analysis of GEMINI 1 data. Pts with active, moderate-to-severe UC were randomized to receive double-blind placebo (PBO) or VDZ at weeks (wks) 0 and 2 during the 6-wk induction phase. Mayo clinic SF subscores (SFS) and RB subscore (RBS) were evaluated at 0, 2, 4, and 6 wks. Mean subscores and mean percent change from baseline (BL) were reported for the overall population and in those who were tumor necrosis factor antagonist (anti-TNF) naïve. The percentages of pts who reached SFS≤1 and/or RBS=0 were also determined. RESULTS: In anti-TNF-naïve pts, greater percentage decreases in mean SFS from BL were observed with VDZ vs PBO, reaching statistical significance at wks 4 and 6 as suggested by the non-overlapping 95% confidence intervals. Percent change from baseline (95%CI) at wks 2, 4, and 6 were -19.9(-28.0, -11.8), -35.7(-45.2, -26.2) and -36.5(-45.0, -28.0) respectively for VDZ and -5.0(-15.7, 5.7), -0.4(-12.8, 11.9) and -12(-23.4, -0.6) respectively for PBO. The same trends were observed in the overall population without reaching statistical significance. Percent change from baseline (95%CI) at wks 2, 4, and 6 were -12.3(-18.6, -6.0), -23.5(-31.2, -15.7) and -25.0(-31.6, -18.3) respectively for VDZ and -6.4(-14.2, 1.5), -9.9(-19.5, -0.3), and -12.4(-20.8, -4.0) respectively for PBO. Similarly, a numerically greater percentage decrease from BL in RBS was observed with VDZ vs PBO, reaching statistical significance at wk 6 in both anti-TNF-naïve and overall populations. Percent change from baseline (95%CI) at wks 2, 4, and 6 for anti-TNF-naïve pts were -29.8(-39.2, -20.4), -45.6(-55.4, -35.9) and -59.0(-67.6, -50.3) respectively for VDZ, and -19.8 (-32.3, -7.3), -28.0(-40.8, -15.3) and -27.1(-38.7, -15.4) respectively for PBO. Percent change from baseline (95%CI) at wks 2, 4, and 6 for overall pts were -28.6 (-35.5, -21.6), -42.3(-49.5, -35.1) and -49.5 (-57.0, -41.9) respectively for VDZ and -20.7 (-29.4, -12.1), -29.6(-38.4, -20.7) and -26.8 (-36.3, -17.3) respectively for PBO. Significantly higher percentages of pts achieved SFS≤1 or RBS=0 with VDZ vs PBO at wk 6 (32% higher with 95%CI:19.5-44.6 and 22.9% higher with 95%CI:9.8-36.0, respectively) and as early as wk 2 (22.2% higher with 95%CI of 9.6-34.9 and 12.3% higher with 95%CI:0.6-24.1, respectively) among the anti-TNF-naïve population. A composite of SFS≤1 and RBS=0 was achieved in a significantly greater percentage of pts with VDZ than PBO at all time points for both anti-TNF naïve and overall populations with treatment differences of 15.7% and 9.0% at Week 2. CONCLUSION(S): Symptomatic improvements were achieved with VDZ as early as wk 2, with greater differences from PBO observed in anti-TNF-naïve pts. These results highlight the rapid onset of VDZ in UC; however, assessing efficacy at wk 14 and beyond for those who exhibit a more gradual response should be used to inform clinical practice.