Exposure–efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn’s disease and ulcerative colitis

ABSTRACT

Background and aims

This posthoc analysis of the GEMINI and VISIBLE studies in ulcerative colitis (UC) and Crohn's Disease (CD) assessed exposure−efficacy of vedolizumab intravenous (IV) and subcutaneous (SC).

Methods

A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (C_av,ss, C_trough,ss) and simulate the transition from vedolizumab IV to SC. Efficacy was defined as clinical remission at week 52: complete Mayo score ≤ 2 points and no individual subscore > 1 point (UC), and CD activity index score ≤ 150 points (CD).

Results

Data were from 1968 patients (GEMINI 1 [n = 334], VISIBLE 1 [n = 216], GEMINI 2 [n = 1009], VISIBLE 2 [n = 409]) who received maintenance treatment with vedolizumab IV-Q8W, IV-Q4W, SC-Q2W, or placebo. Model-predicted C_av,ss for IV-Q8W and SC-Q2W was similar in UC and CD. C_av,ss was higher for IV-Q4W than IV-Q8W and SC-Q2W. C_trough,ss values from IV and SC aligned well with pooled observed C_trough by treatment group in UC and CD. C_av,ss was equivalent for SC and IV. For UC and CD, efficacy rates were greater in patients in the highest quartiles of vedolizumab exposure for both formulations.

Conclusion

Exposure−efficacy relationships for IV and SC vedolizumab administration were comparable, confirming that both are equally effective during maintenance treatment.

KEYWORDS:

• Efficacy
• exposure
• pharmacokinetics
• ulcerative colitis
• vedolizumab
• crohn's disease

Declaration of interest

G D’Haens is a consultant for AbbVie, AgomAb, AM Pharma, AMT, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Gilead, GlaxoSmithKline, Gossamer Bio, Immunic, Index, Johnson & Johnson, Kaleido, Origo, Pfizer, Polpharma, Procise Diagnostics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist, and Roche, and reports serving on speaker’s bureau for AbbVie, Arena, Bristol Myers Squibb, Galapagos, Gilead, Pfizer, and Takeda. M Rosario was an employee of the study sponsor, Takeda, at the time of this study. D Polhamus and NL Dirks are employees of Metrum Research Group. C Chen, K Kisfalvi, and C Agboton are employees of the study sponsor, Takeda. S Vermeire reports grant support from AbbVie, Merck Sharp & Dohme, Pfizer, and Takeda; speaker fees from AbbVie, Dr Falk, Ferring, Hospira, Merck Sharp & Dohme, Pfizer, Takeda, and Tillots; and consulting fees from AbbVie, Celgene, Ferring, Galapagos, Genentech/Roche, Hospira, Janssen, Merck Sharp & Dohme, Mundipharma, Pfizer, Second Genome, Shire, and Takeda. BG Feagan has received consulting fees from AbbVie, ActoGeniX, Albireo, Allergan, Amgen, AstraZeneca, Atlantic, Avaxia, Axcan, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Elan/Biogen, Eli Lilly, EnGene, Ferring, GICare, Gilead, Given Imaging, GlaxoSmithKline, Ironwood, Johnson & Johnson/Janssen, Kyowa Hakko Kirin, Lexicon, Lycera, Merck, Mesoblast, Millennium, Nektar, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics & Diagnostics, Protagonist, Receptos, Roche/Genentech, Salix, Shire, Serono, Sigmoid, Synergy, Takeda, Teva, TiGenix, Tillotts, UCB, Warner-Chilcott, Wyeth, Zealand, and Zyngenia; speaker fees from AbbVie, Johnson & Johnson/Janssen, Takeda, and UCB; financial support for research from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic, Boehringer Ingelheim, Celgene, Celltech, Genentech/Hoffmann-La Roche, Gilead, GlaxoSmithKline, Janssen Research & Development, Pfizer, Receptos/Celgene, Sanofi, Santarus, Takeda Development Center Americas, Tillotts, and UCB; and is a member of the Board of Directors of Robarts Clinical Trials. WJ Sandborn reports research grants from AbbVie, Abivax, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Genentech, Gilead, GlaxoSmithKline, Janssen, Pfizer, Prometheus Biosciences, Seres, Shire, Takeda, and Theravance Biopharma; consulting fees from AbbVie, Abivax, Alfasigma, Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust), Allakos, Amgen, Arena, AstraZeneca, Atlantic, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, ClostraBio, Eli Lilly, Forbion, Galapagos, Genentech (Roche), GlaxoSmithKline, Gossamer Bio, Index, iota, Janssen, Morphic, Novartis, Oppilan (now Ventyx Biosciences), Pfizer, Pharm-Olam, Polpharma, Progenity, Prometheus Biosciences, Protagonist, PTM, Seres, Shoreline, Sublimity, Surrozen, Takeda, Theravance Biopharma, Vedanta, Ventyx, Vimalan, Vivreon Gastrosciences, Xencor, and Zealand; stock or stock options in Allakos, BeiGene, Gossamer Bio, Oppilan (now Ventyx Biosciences), Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist, Shoreline, Ventyx, Vimalan, and Vivreon Gastrosciences; and is an employee of Shoreline. Spouse of WJ Sandborn reports being a consultant and holding stock options in Iveric Bio and Prometheus Laboratories; stock or stock options in Oppilan (now Ventyx Biosciences), Progenity, Ventyx, and Vimalan; and is an employee of and holds stock or stock options in Prometheus Biosciences.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2024.2318465.

Ethics statement

All four studies analyzed in this paper were conducted in agreement with the principles set out in the Declaration of Helsinki and were approved by national and institutional ethics committees. All participants provided written informed consent before entry into the studies.

Author contributions

M Rosario, D Polhamus, NL Dirks, C Chen, K Kisfalvi, and C Agboton contributed to the acquisition, analysis, and interpretation of the pharmacokinetic data. G D’Haens, S Vermeire, BG Feagan, and WJ Sandborn were primary investigators in the clinical trials on which the pharmacokinetic modeling was based and contributed to the interpretation of the data. All authors collectively contributed to the development of the manuscript and approved the final version for submission.

Data availability statement

The datasets – including the redacted study protocol, redacted statistical analysis plan, and individual participants’ data supporting the results reported in this article – will be available 3 months from initial request, to researchers who provide a methodologically sound proposal. The data will be provided after their de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.

Acknowledgments

This work was funded by Takeda. Medical writing assistance was provided by Paul Hassan, PhD, of Excel Scientific Solutions, Horsham, UK, and was funded by Takeda. This work was presented in part at the 2019 European Crohn’s and Colitis Organization Congress, March 6-9, Copenhagen, Denmark, and the 2020 European Crohn’s and Colitis Organization Congress, February 12-15, Vienna, Austria.

Additional information

Funding

This work was supported by Takeda.