-
Tytuł:
-
Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn's Disease.
-
Autorzy:
-
Danese S; IBD Center, Humanitas Clinical and Research Center, Humanitas University, Rozzano, Milan, Italy. Electronic address: .
Sandborn WJ; University of California, San Diego, La Jolla, California.
Colombel JF; Icahn School of Medicine at Mount Sinai, New York City, New York.
Vermeire S; University Hospitals Leuven, Leuven, Belgium.
Glover SC; University of Florida, Gainesville, Florida.
Rimola J; Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
Siegelman J; Takeda Development Center Americas Inc., Cambridge, Massachusetts.
Jones S; Takeda Development Centre Europe Ltd, London, UK.
Bornstein JD; Takeda Development Center Americas Inc., Cambridge, Massachusetts.
Feagan BG; Robarts Clinical Trials, Western University, London, Ontario, Canada.
-
Źródło:
-
Gastroenterology [Gastroenterology] 2019 Oct; Vol. 157 (4), pp. 1007-1018.e7. Date of Electronic Publication: 2019 Jul 04.
-
Typ publikacji:
-
Clinical Trial, Phase III; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: Philadelphia, PA : W.B. Saunders
Original Publication: Baltimore.
-
MeSH Terms:
-
Endoscopy, Gastrointestinal*
Magnetic Resonance Imaging*
Anti-Inflammatory Agents/*therapeutic use
Antibodies, Monoclonal, Humanized/*therapeutic use
Crohn Disease/*drug therapy
Gastrointestinal Agents/*therapeutic use
Intestinal Mucosa/*drug effects
Wound Healing/*drug effects
Adult ; Anti-Inflammatory Agents/adverse effects ; Antibodies, Monoclonal, Humanized/adverse effects ; Biopsy ; Crohn Disease/diagnostic imaging ; Crohn Disease/pathology ; Female ; Gastrointestinal Agents/adverse effects ; Humans ; Intestinal Mucosa/diagnostic imaging ; Intestinal Mucosa/pathology ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Quality of Life ; Remission Induction ; Time Factors ; Treatment Outcome ; Young Adult
-
Contributed Indexing:
-
Keywords: GHAS; Long-Term Outcome; MaRIA; Monoclonal Antibody; α4β7 integrin
-
Molecular Sequence:
-
ClinicalTrials.gov NCT02425111
-
Substance Nomenclature:
-
0 (Anti-Inflammatory Agents)
0 (Antibodies, Monoclonal, Humanized)
0 (Gastrointestinal Agents)
9RV78Q2002 (vedolizumab)
-
Entry Date(s):
-
Date Created: 20190708 Date Completed: 20191022 Latest Revision: 20191022
-
Update Code:
-
20240105
-
DOI:
-
10.1053/j.gastro.2019.06.038
-
PMID:
-
31279871
-
Background & Aims: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy.
Methods: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less).
Results: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naïve to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations.
Conclusions: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD. ClinicalTrials.gov no: NCT02425111.
(Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Comment in: Gastroenterology. 2019 Oct;157(4):925-927. (PMID: 31356804)
Comment in: Gastroenterology. 2020 Mar;158(4):1176-1177. (PMID: 31836531)
Comment in: Gastroenterology. 2020 Mar;158(4):1177-1178. (PMID: 31911101)
