Introduction: Vedolizumab (VDZ), a humanized monoclonal anti-α4β7 integrin antibody, is approved for the treatment of adults with moderately to severely active CD1. Improvements in patient-reported symptoms remain important treatment goals for patients (pts) and key indicators of treatment response for physicians. We aimed to characterize early response with VDZ by evaluating the timing of symptomatic improvements through a post hoc analysis of GEMINI 2. Methods: Pts with active CD were randomized to receive double-blind placebo (PBO) or VDZ at weeks (wks) 0 and 2 during the 6-wk induction phase. The two patient-reported components of the Crohn's disease activity index (CDAI) score- abdominal pain subscores (APS) and number of liquid or very soft stools subscore (NLVSS)- were evaluated at 0, 2, 4 and 6 wks. Mean percentage change from baseline (BL) was reported for the overall population and in those who were tumor necrosis factor antagonist (anti-TNF) naive. The difference in adjusted percentage change from BL between VDZ and PBO was determined using an ANCOVA model with treatment as a factor and BL as a covariate. Results: Percentage decreases in APS and NLVSS from BL over time were examined in anti-TNF-naive and overall populations. Significantly greater percentage decreases in APS were observed with VDZ than PBO at wks 2, 4 and 6 in both populations (Fig 1). Similarly, greater percentage decreases in NLVSS were observed with VDZ than PBO, reaching statistical significance at wks 2 and 6 (Fig 2). A composite score of APS and NLVSS showed similar trends with significantly greater percentage decreases with VDZ than PBO at all time points (Fig 3). Overall, differences in percentage change between VDZ and PBO were greater in naive pts than in the overall population. Notably, differences in percentage APS decrease from BL in naive pts were about 2-times as much as in the overall population [% decrease in naive vs overall: -19.4 vs -10.4; -22.0 vs -11.2; -21.1 vs -11.7 at wks 2, 4 and 6, respectively](Fig 1).Figure: Percentage change from baseline in CDAI abdominal pain score *Data points represent adjusted % change from BL mean, where adjustment is for BL value and treatment. Error bars represent standard error. †Diff in adjusted % change from BL=adjusted mean % change for VDZ - adjusted mean % change for PBO. Upper limit of 95% CI <0 indicates statistical significance at a nominal significance level of 0.05. Patients with BL APS=0 were excluded from this analysis. Abbreviations: anti-TNF, tumor necrosis factor antagonist; APS, abdominal pain subscore; BL, baseline; CDAI, Crohn's disease activity index; CI, confidence interval; Diff, difference; PBO, placebo; VDZ, vedolizumab.Figure: Percentage change from baseline in CDAI number of liquid or very soft stool subscore *Data points represent adjusted % change from BL mean, where adjustment is for BL value and treatment. Error bars represent standard error. †Diff in adjusted % change from BL=adjusted mean % change for VDZ - adjusted mean % change for PBO. Upper limit of 95% CI <0 indicates statistical significance at a nominal significance level of 0.05. Patients with BL NLVSS=0 were excluded from this analysis. Abbreviations: anti-TNF, tumor necrosis factor antagonist; BL, baseline; CDAI, Crohn's disease activity index; CI, confidence interval; Diff, difference; PBO, placebo; VDZ, vedolizumab.Figure: Percentage change from baseline in CDAI composite score of the number of liquid or very soft stool and abdominal pain *Data points represent adjusted % change from BL mean, where adjustment is for BL value and treatment. Error bars represent standard error. †Diff in adjusted % change from BL=adjusted mean % change for VDZ - adjusted mean % change for PBO. Upper limit of 95% CI <0 indicates statistical significance at a nominal significance level of 0.05. Patients with BL value=0 were excluded from this analysis. Abbreviations: anti-TNF, tumor necrosis factor antagonist; BL, baseline; CDAI, Crohn's disease activity index; CI, confidence interval; Diff, difference; PBO, placebo; VDZ, vedolizumab.Conclusion: Symptomatic improvements were achieved with VDZ as early as wk 2, with greater differences from PBO observed in anti-TNF-naive pts compared with the overall population. These results highlight that rapid onset of action of VDZ in CD may be observed in some pts; however, for those who exhibit a more gradual response, assessing efficacy at wk 14 and beyond is recommended to inform clinical practice.