Week 2 Symptomatic Response with Vedolizumab as a Predictive Factor in Japanese Anti-TNFα-Naive Patients with Ulcerative Colitis: A post hoc Analysis of a Randomized, Placebo-Controlled Phase 3 Trial.


Journal

Digestion
ISSN: 1421-9867
Titre abrégé: Digestion
Pays: Switzerland
ID NLM: 0150472

Informations de publication

Date de publication:
2021
Historique:
received: 03 06 2020
accepted: 11 10 2020
pubmed: 18 1 2021
medline: 4 9 2021
entrez: 17 1 2021
Statut: ppublish

Résumé

To evaluate the onset of symptomatic response with vedolizumab in patients with moderate-to-severe ulcerative colitis in Japan. Patients were randomized to receive vedolizumab 300 mg or placebo at Weeks 0, 2, and 6. Mayo subscores were analyzed in patients with baseline stool frequency (SF) ≥1 and rectal bleeding (RB) ≥1. In patients with baseline SF ≥2 and RB ≥1, the proportion who achieved SF ≤1 and RB = 0 was determined. Patients were randomized to vedolizumab (n = 164) or placebo (n = 82). Decrease from baseline in mean SF subscore was greater with vedolizumab versus placebo from Week 2 (-6.6%; 95% confidence interval [CI], -16.2, 3.0), with a greater difference in anti-tumor necrosis factor (TNF)α-naive patients (vedolizumab vs. placebo, -13.2%; 95% CI, -29.7, 3.3). Mean percentage decrease from baseline RB subscore was numerically greater with vedolizumab versus placebo from Week 6 in anti-TNFα-naive patients (-10.7%; 95% CI, -33.0, 11.5). More patients in the anti-TNFα-naive subgroup achieved SF ≤1 and RB = 0 with vedolizumab versus placebo at Week 2 (14.8%; 95% CI, 2.5, 27.0) and Week 6 (20.3%; 95% CI, 4.4, 36.2). Patients with SF ≤1 and RB = 0 at Week 2 had higher clinical response, clinical remission, and mucosal healing rates at Week 10 than those without. Our results indicate that vedolizumab induces a rapid symptomatic response, particularly in anti-TNFα-naive patients, and suggest that early symptomatic improvement predicts treatment response at Week 10 (NCT02039505).

Sections du résumé

BACKGROUND AND AIM OBJECTIVE
To evaluate the onset of symptomatic response with vedolizumab in patients with moderate-to-severe ulcerative colitis in Japan.
METHODS METHODS
Patients were randomized to receive vedolizumab 300 mg or placebo at Weeks 0, 2, and 6. Mayo subscores were analyzed in patients with baseline stool frequency (SF) ≥1 and rectal bleeding (RB) ≥1. In patients with baseline SF ≥2 and RB ≥1, the proportion who achieved SF ≤1 and RB = 0 was determined.
RESULTS RESULTS
Patients were randomized to vedolizumab (n = 164) or placebo (n = 82). Decrease from baseline in mean SF subscore was greater with vedolizumab versus placebo from Week 2 (-6.6%; 95% confidence interval [CI], -16.2, 3.0), with a greater difference in anti-tumor necrosis factor (TNF)α-naive patients (vedolizumab vs. placebo, -13.2%; 95% CI, -29.7, 3.3). Mean percentage decrease from baseline RB subscore was numerically greater with vedolizumab versus placebo from Week 6 in anti-TNFα-naive patients (-10.7%; 95% CI, -33.0, 11.5). More patients in the anti-TNFα-naive subgroup achieved SF ≤1 and RB = 0 with vedolizumab versus placebo at Week 2 (14.8%; 95% CI, 2.5, 27.0) and Week 6 (20.3%; 95% CI, 4.4, 36.2). Patients with SF ≤1 and RB = 0 at Week 2 had higher clinical response, clinical remission, and mucosal healing rates at Week 10 than those without.
CONCLUSIONS CONCLUSIONS
Our results indicate that vedolizumab induces a rapid symptomatic response, particularly in anti-TNFα-naive patients, and suggest that early symptomatic improvement predicts treatment response at Week 10 (NCT02039505).

Identifiants

pubmed: 33454706
pii: 000512235
doi: 10.1159/000512235
pmc: PMC8491515
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Gastrointestinal Agents 0
Tumor Necrosis Factor-alpha 0
vedolizumab 9RV78Q2002

Banques de données

ClinicalTrials.gov
['NCT02039505']

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

742-752

Informations de copyright

The Author(s). Published by S. Karger AG, Basel.

Références

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Auteurs

Masakazu Nagahori (M)

Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan, nagahori.gast@tmd.ac.jp.

Kenji Watanabe (K)

Department of Intestinal Inflammation Research, Hyogo College of Medicine, Hyogo, Japan.

Satoshi Motoya (S)

IBD Center, Hokkaido Prefectural Welfare Federation of Agricultural Cooperatives, Sapporo-Kosei General Hospital, Sapporo, Japan.

Haruhiko Ogata (H)

Endoscopic Center, Keio University School of Medicine, Tokyo, Japan.

Takanori Kanai (T)

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

Toshiyuki Matsui (T)

Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.

Yasuo Suzuki (Y)

Department of Internal Medicine, Toho University Medical Center Sakura Hospital, Chiba, Japan.

Philippe Pinton (P)

Japan Medical Office, Takeda Pharmaceutical Co., Ltd., Tokyo, Japan.

Lyann Ursos (L)

Global Medical Affairs, Takeda Pharmaceuticals USA, Inc., Deerfield, Illinois, USA.

Shigeru Sakamoto (S)

Takeda Development Center Japan, Takeda Pharmaceutical Co., Ltd., Osaka, Japan.

Mitsuhiro Shikamura (M)

Takeda Development Center Japan, Takeda Pharmaceutical Co., Ltd., Osaka, Japan.

Tetsuharu Hori (T)

Takeda Development Center Japan, Takeda Pharmaceutical Co., Ltd., Osaka, Japan.

Jovelle Fernandez (J)

Japan Medical Office, Takeda Pharmaceutical Co., Ltd., Tokyo, Japan.

Toshifumi Hibi (T)

Center for Advanced Inflammatory Bowel Disease Research and Treatment, Kitasato Institute Hospital, Kitasato University, Tokyo, Japan.

Mamoru Watanabe (M)

Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

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Classifications MeSH