Real-world multicentre observational study including population pharmacokinetic modelling to evaluate the exposure–response relationship of vedolizumab in inflammatory bowel disease: ERELATE Study

Niels Vande Casteele*, William J. Sandborn, Brian G. Feagan, Séverine Vermeire, Parambir S. Dulai, Andres Yarur, Xavier Roblin, Shomron Ben-Horin, Iris Dotan, Mark T. Osterman, Maria Rosario, Teresa Mc Rorie Osborn, Julian Panes, Dirk Lindner, Christian Agboton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: ERELATE was a phase 4, multinational, retrospective, observational study. Aim: To evaluate the relationship between intravenous vedolizumab exposure and treatment outcomes over 52 weeks in adults with ulcerative colitis (UC) or Crohn’s disease (CD). Methods: Real-world data from patients with UC or CD treated with intravenous vedolizumab in nine centres in six countries were collected retrospectively. Treatment outcomes were collected at Weeks 14, 26 and 52. An established population pharmacokinetic model (incorporating observed vedolizumab concentrations based on a Bayesian approach) was used to predict individual vedolizumab exposure. Vedolizumab exposure–response relationship was evaluated overall, by indication and based on baseline characteristics. Results: The study population (n = 695; UC, n = 304; CD, n = 391) had a median age of 39 years; 47.9% were male and 86.9% had prior tumour necrosis factor antagonist exposure. By Week 14, clinical, endoscopic, deep (clinical plus endoscopic) and biologic remission was achieved by 47.3%, 59.6%, 30.7% and 19.0% of patients respectively. Higher vedolizumab trough concentration early in treatment was consistently associated with clinical remission at later time points. Clinical remission at Week 14 and Week 52 was associated with Week 6 trough concentrations of ≥31.0 and ≥32.0 μg/ml respectively. Importantly, multivariable analysis identified baseline clearance as the only exposure measure predictive of clinical and deep remission at Week 52. Conclusions: In this real-world study, a positive exposure–response relationship was observed for vedolizumab. Vedolizumab concentration during induction may be an important predictor of short- and long-term outcomes, and similarly, vedolizumab baseline clearance may be an important predictor of remission.

Original languageEnglish
Pages (from-to)463-476
Number of pages14
JournalAlimentary Pharmacology and Therapeutics
Volume56
Issue number3
DOIs
StatePublished - Aug 2022

Funding

FundersFunder number
Abbott/AbbVie
Alimentiv Health Trust
Johnson & Johnson/Janssen
Mundipharma
Prometheus Bioscience
Prometheus Biosciences
SecondGenome
Theradiag
Tillotts
Vendata Biosciences
Ventyx Biosciences
Vimalan Biosciences and Vivreon Biosciences
Vimalan Biosciences, Vivelix, Vivreon Biosciences and Zealand
Wild Biotech
Boehringer Ingelheim
AMGEN
Bristol-Myers Squibb
Pfizer
AstraZeneca
GlaxoSmithKline
Johnson and Johnson
Gilead Sciences
Janssen Biotech
Teva Pharmaceutical Industries
Takeda Pharmaceutical Company
Janssen Pharmaceuticals
Merck Sharp and Dohme
School of Public Health, University of California Berkeley
Hospira
Kyowa Hakko Kirin
Ferring Pharmaceuticals

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