DOP84 Early treatment responses within 14 days of intravenous vedolizumab induction therapy for Crohn’s Disease: Post hoc analysis of patient-reported outcomes from the VISIBLE 2 study
D'Haens, G.(1);Baert, F.(2);Danese, S.(3);Kobayashi, T.(4);Loftus Jr., E.V.(5);Sandborn, W.J.(6);Dornic, Q.(7);Lindner, D.(7);Kisfalvi, K.(8);Marins, E.G.(8);Vermeire, S.(9)
(1)Amsterdam University Medical Centers, Department of Gastroenterology, Amsterdam, The Netherlands;(2)AZ Delta, Department of Gastroenterology, Roeselare, Belgium;(3)Humanitas University, Department of Gastroenterology, Milan, Italy;(4)Kitasato University Kitasato Institute Hospital, Center for Advanced IBD Research and Treatment, Tokyo, Japan;(5)Mayo Clinic College of Medicine, Division of Gastroenterology and Hepatology, Rochester, United States;(6)University of California San Diego, Department of Medicine, San Diego, United States;(7)Takeda, Statistical and Quantitative Science, Zurich, Switzerland;(8)Takeda, Global Medical Affairs, Cambridge, United States;(9)University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium
Background
Vedolizumab (VDZ), an anti-a4β7 integrin antibody that selectively blocks lymphocyte trafficking to the gut, is approved for the treatment of adult patients with moderate-to-severe Crohn’s disease (CD). This post hoc analysis of data from the VISIBLE 2 trial evaluated early patient-reported outcomes assessed within the first 14 days of VDZ induction.
Methods
VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a phase 3, multicentre, placebo-controlled study, evaluating the efficacy and safety of subcutaneous VDZ for maintenance treatment in patients with moderately to severely active CD. Efficacy was assessed based on CD Activity Index (CDAI). Patients received induction treatment with intravenous (IV) VDZ 300 mg open-label at Weeks 0 and 2. For this analysis, responses to VDZ were assessed using CDAI sub-scores for patient-reported abdominal pain (AP) and stool frequency (SF) collected daily via electronic diary in the first 14 days of VDZ treatment (Day 1 to 15) in all patients receiving ≥1 VDZ dose at induction. Descriptive statistics were used.
Results
The analysis included 611 patients (mean [SD] age 37.6 [13.4] years; CD duration 9.0 [8.1] years); 323 (53%) were male; 228 (37%) had severe disease (CDAI >330) at baseline; and 350 (57%) were anti-TNF-experienced. In the first 14 days of VDZ IV induction, the rate of patients with daily SF≤3 increased from 30% at baseline (Day 1) to 47.7% on Day 15. Increases were similar in both anti-TNF-naïve vs. anti-TNF-experienced patients and in patients with severe vs. moderate disease (Figure 1). Mean baseline SF was reduced from 6.4 to 5.0 at Day 15 in patients with severe disease and from 4.3 to 3.5 in patients with moderate disease. Overall, the proportion of patients rating AP as severe/moderate declined from baseline to Day 15 of induction (from 14.6% to 8.2% for severe AP and from 60.7% to 40.6% for moderate AP). Similar Day 1-to-15 reductions were reported in both anti-TNF-naïve (severe AP: 14.2% to 9.2%; moderate AP: 62.6% to 44.6%) and anti-TNF-experienced patients (severe AP: 14.8% to 7.4%; moderate AP: 59.3% to 37.7%), respectively. Although a minority of patients (6.3%) in the sub-group with moderate AP at baseline had worse pain at Day 15, there were early improvements in AP ratings for most patients reporting severe or moderate AP at baseline (Figure 2).
Conclusion
This post hoc analysis of daily patient-reported SF and AP in the VISIBLE 2 CD study indicates an early onset of response to VDZ IV induction within the first 14 days of treatment.
