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 language | English (US) |
|---|---|
| Pages (from-to) | 463-476 |
| Number of pages | 14 |
| Journal | Alimentary Pharmacology and Therapeutics |
| Volume | 56 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 2022 |
Funding
This work was supported by Takeda. Medical writing support was provided by Daniella Babu, PhD, and Eleanor Ling, PhD, of Excel Medical Affairs, and funded by Takeda. Funding information We thank the patients who participated in the trial, their caregivers and the study investigators and members of the ERELATE study team. Declaration of personal interests: NVC has received research grants and personal fees from R-Biopharm, Takeda and UCB, and personal fees from Alimentiv, Celltrion and Prometheus. WJS has received research grants from AbbVie, Abivax, Arena, Boehringer Ingelheim, Celgene, Genentech, Gilead, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus, Seres, Shire, Takeda and Theravance; consulting fees from AbbVie, Abivax, AdMIRx, Alfasigma, Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust), Alivio, Allakos, Amgen, Applied Molecular Transport, Arena, Bausch Health (Salix), BeiGene, Bellatrix, Boehringer Ingelheim, Boston, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo, Equillium, Escalier, Forbion, Genentech/Roche, Gilead, Glenmark, Gossamer Bio, Immunic (Vital Therapies), Index, Intact, Janssen, Kyverna, Landos, Lilly, Oppilan, Otsuka, Pandion, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, Reistone, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance, Thetis, Tillotts, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix, Vivreon Biosciences and Zealand; and stock/stock options in Allakos, BeiGene, Gossamer Bio, Oppilan, Prometheus Biosciences, Prometheus Laboratories, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences and Vivreon Biosciences. The spouse of WJS reports consultant fees from and stock options in Iveric Bio, Oppilan and Prometheus Laboratories; stock/stock options in Progenity, Ventyx Biosciences and Vimalan Biosciences; and is an employee of and holds stock/stock options in Prometheus Biosciences. BGF reports consultant fees from Abbott/AbbVie, ActoGeniX, Akros, Albireo, Amgen, AstraZeneca, Avaxia, Avir, Axcan, Baxter Healthcare, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring, gIcare, Gilead, Given Imaging, GlaxoSmithKline, Ironwood, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Kyowa Hakko Kirin, Lexicon, Lilly, Lycera, Merck, Mesoblast, Millennium, Nektar, Nestlé, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Roche/Genentech, Salix, Serono, Shire, Sigmoid, Synergy, Takeda, Teva, TiGenix, Tillotts, UCB, Vertex, VHsquared, Warner Chilcott, Wyeth, Zealand and Zyngenia; grant/research support from Abbott/AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Millennium, Pfizer, Receptos, Roche/Genentech, Sanofi, Santarus, Tillotts, UCB; and membership (board of directors) of Robarts Clinical Trials. SV reports financial support for research from AbbVie, Johnson & Johnson, Pfizer and Takeda; lecture fees from AbbVie, Centocor, Ferring, Genentech/Roche, Hospira, Johnson & Johnson, Merck Sharp & Dohme, Pfizer, Takeda and Tillotts; and consultant fees from AbbVie, Abivax, Celgene, Celltrion, Centocor, Ferring, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Hospira, Johnson & Johnson, Merck Sharp & Dohme, Mundipharma, Pfizer, ProDigest, Prometheus, SecondGenome, Takeda and Tillotts. PSD reports consultant fees from AbbVie, Janssen, Pfizer and Takeda, and research support from AbbVie, Bulhmann, Janssen, Polymedco, Prometheus and Takeda. AY reports consultant fees from Arena, Bristol Myers Squibb, Prometheus Bioscience and Takeda. XR reports funding from AbbVie, Amgen, Biogen, Gilead, Janssen, Merck Sharp & Dohme, Pfizer, Takeda and Theradiag. SB-H reports consultant fees/advisory boards for AbbVie, Celltrion, Galmed, GlaxoSmithKline, Janssen, Pfizer and Takeda, and research support from AbbVie, Celltrion, Galmed, Janssen and Takeda. ID reports consultant fees/advisory boards for Abbott, AbbVie, Arena, Athos, Cambridge Healthcare, Celgene/Bristol Myers Squibb, Celltrion, DSM, Ferring, Food Industries Organization, Galapagos, Gilead, Integra Holdings, Iterative Scopes, Janssen, Neopharm, Pfizer, Rafa Laboratories, Roche/Genentech, Sangamo, Sublimity, Takeda and Wild Biotech; speaker fees from AbbVie, Altman, Celgene/Bristol Myers Squibb, Celltrion, Falk, Ferring, Genentech, Janssen, Nestlé, Pfizer and Takeda; and research support from AbbVie, Altman and Pfizer. MTO reports financial support for research from UCB; consultant fees from AbbVie, Bristol Myers Squibb, Elan, Janssen, Lycera, Merck, Pfizer, Roche/Genentech, Takeda and UCB. MR was an employee of Takeda at the time this research was conducted and is an inventor on granted patents and pending patent applications relating to the clinical pharmacology of vedolizumab. TMO was an employee of Takeda at the time this research was conducted and holds stock/stock options in Takeda. JP reports financial support for research from AbbVie and Pfizer; lecture fees from AbbVie, Johnson & Johnson, Pfizer and Takeda, and consultant fees from AbbVie, Arena, Boehringer Ingelheim, Celgene, Celltrion, GlaxoSmithKline, Immunic, Nestlé, Origo, Pandion, Pfizer, Progenity, Takeda, Theravance and Wasserman. DL and CA are employees of and hold stock/stock options in Takeda.
ASJC Scopus subject areas
- Hepatology
- Gastroenterology
- Pharmacology (medical)