Gastroenterology

Gastroenterology

Volume 158, Issue 3, February 2020, Pages 562-572.e12
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis

https://doi.org/10.1053/j.gastro.2019.08.027Get rights and content
Under a Creative Commons license
open access

Background & Aims

Maintenance treatment with vedolizumab, a monoclonal antibody that inhibits the gut-selective α4β7 integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of vedolizumab for maintenance treatment. Subcutaneous vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis.

Methods

We performed a phase 3, double-blind, double-dummy trial at 141 sites in 29 countries from December 18, 2015 through August 21, 2018. Patients with moderately to severely active ulcerative colitis received open-label treatment with intravenous vedolizumab 300 mg at weeks 0 and 2. At week 6, patients with clinical response were randomly assigned maintenance treatment with subcutaneous vedolizumab 108 mg every 2 weeks, intravenous vedolizumab 300 mg every 8 weeks, or placebo. The primary end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1.

Results

Among the randomized 216 patients, clinical remission at week 52 was achieved by 46.2%, 42.6%, and 14.3% of patients in the subcutaneous vedolizumab, intravenous vedolizumab, and placebo groups, respectively (subcutaneous vedolizumab vs placebo: Δ32.3%; 95% confidence interval, 19.7%–45.0%; P < .001). The subcutaneous vedolizumab group also had greater endoscopic improvement and durable clinical response at week 52 compared with placebo (both P < .001). The incidence of injection-site reactions was more frequent in patients given subcutaneous vedolizumab (10.4%) than intravenous vedolizumab (1.9%) or placebo (0%); these were not treatment limiting, most were mild, and none resulted in discontinuation. Subcutaneous and intravenous vedolizumab safety profiles were otherwise similar.

Conclusions

Subcutaneous vedolizumab is effective as maintenance therapy in patients with moderately to severely active ulcerative colitis who had a clinical response to intravenous vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14.

Keywords

VISIBLE 1
UC
Inflammatory Bowel Disease
Long-Term Therapy

Abbreviations used in this paper

AE
adverse event
AVA
anti-vedolizumab antibody
Cavg,ss
average serum concentration at steady state
CI
confidence interval
Ctrough,ss
trough concentrations at steady state
EQ-5D
EuroQoL-5D
ISR
injection-site reaction
IV
intravenous
MedDRA
Medical Dictionary for Regulatory Activities
PK
pharmacokinetic
SC
subcutaneous
TNF
tumor necrosis factor
UC
ulcerative colitis

Cited by (0)

Conflicts of interestThe authors disclose the following: William J. Sandborn: Financial support for research: Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, AbbVie, Janssen, Takeda, Lilly, Celgene/Receptos, Pfizer, Prometheus Laboratories; Consulting fees: Abbvie, Allergan, Amgen, Arena Pharmaceuticals, Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Genentech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust, HART), Series Therapeutics, Shire, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tigenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals; Stock or stock options: BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Precision IBD, Progenity, Ritter Pharmaceuticals, Ventyx Biosciences, Vimalan Biosciences. Spouse: Opthotech–consultant, stock options; Progenity–consultant, stock; Oppilan Pharma–employee, stock options; Escalier Biosciences–employee, stock options; Precision IBD–employee, stock options; Ventyx Biosciences–employee, stock options; Vimalan Biosciences–employee, stock options. Filip Baert: Financial support for research: AbbVie, Chiesi, Ipsen, MSD, Roche; Consultancy: AbbVie, Celgene, Falk, Ferring, Janssen, Mundipharma, MSD, Pfizer, Takeda, Vifor. Silvio Danese: Lecture fees: AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, Boehringer Ingelheim; Consultancy: AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, Boehringer Ingelheim. Željko Krznarić: Lecture fees: AbbVie, Hospira, Johnson & Johnson, MSD, Oktal Pharma. Taku Kobayashi: Financial support for research: EA Pharma, Thermo Fisher Scientific, Alfresa Pharma, and Nippon Kayaku. Lecture fees: Mitsubishi Tanabe Pharma, Pfizer, Eisai, Kyorin Pharmaceutical, AbbVie, Janssen, JIMRO, Ajinomoto Pharma, EA Pharma, Astellas Pharma, Mochida Pharmaceutical, Asahi Kasei Medical, Takeda, Gilead Sciences, Celltrion, Nippon Kayaku, Alfresa Pharma; Consultancy: Janssen, Pfizer, Kyorin Pharmaceutical, Mochida Pharmaceutical, Takeda, Eli Lilly, Ferring Pharmaceutical, Nippon Kayaku, Thermo Fisher Scientific, Covidien Japan. Xiaopan Yao: Employee of Takeda at the time the study was conducted. Jingjing Chen: Employee of Takeda. Maria Rosario: Employee of Takeda. Siddharth Bhatia: Employee of Takeda. Krisztina Kisfalvi: Employee of Takeda. Geert D’Haens: Lecture fees: AbbVie, Biogen, Ferring, Johnson & Johnson, Merck Sharp Dohme, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millennium/Takeda, Tillotts and Vifor; Consultancy: AbbVie, Ablynx, Allergan, Amakem, Amgen, AM Pharma, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Echo Pharmaceuticals, Eli Lilly, Engene, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Gossamerbio, Hospira/Pfizer, Immunic, Johnson & Johnson, Lycera, Medimetrics, Millennium/Takeda, Mitsubishi Pharma, Merck Sharp Dohme, Mundipharma, Nextbiotics, Novo Nordisk, Otsuka, Pfizer/Hospira, Photopill, Prometheus Laboratories/Nestle, Progenity, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor. Séverine Vermeire: Financial support for research: MSD, AbbVie, Takeda, Pfizer, Johnson & Johnson; Lecture fees: MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, Johnson & Johnson, Genentech/Roche; Consultancy: MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, Johnson & Johnson, Genentech/Roche, Celgene, Mundipharma, Celltrion, SecondGenome, Prometheus, Gilead, Galapagos, ProDigest.

FundingThis study was sponsored by Takeda. Personnel from the study sponsor designed the trial in conjunction with the principal investigators. Takeda analyzed the data, and with all authors jointly interpreted the results.

Author names in bold designate shared co-first authorship.