The relationship among vedolizumab drug concentrations, biomarkers of inflammation, and clinical outcomes in a Canadian real-world study.

Autor:	Seow CH; Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada., Marshall JK; Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton Ontario, Canada., Stewart E; Pentavere Research Group Inc., Toronto, ON, Canada., Pettengell C; Pentavere Research Group Inc., Toronto, ON, Canada., Ward R; Takeda Canada Inc., Toronto, ON, Canada., Afif W; Division of Gastroenterology, McGill University Health Centre (MUHC), Montreal General Hospital, Montreal, QC, Canada.
Jazyk:	angličtina
Zdroj:	Journal of the Canadian Association of Gastroenterology [J Can Assoc Gastroenterol] 2024 Mar 24; Vol. 7 (4), pp. 290-298. Date of Electronic Publication: 2024 Mar 24 (Print Publication: 2024).
DOI:	10.1093/jcag/gwae010
Abstrakt:	Background and Aims: Therapeutic drug monitoring is used to optimize anti-tumour necrosis factor biologic effectiveness in inflammatory bowel disease, but its role with other biological classes is unclear. This study explores relationships between post-induction vedolizumab trough concentrations and biochemical outcomes in a real-world study of individuals with inflammatory bowel disease. Methods: This retrospective analysis of data from a national patient support program between 2018 and 2020, included 436 individuals with Crohn's disease or ulcerative colitis receiving vedolizumab. Optimal vedolizumab concentration thresholds (at weeks 6 and 14) were determined based on their ability to predict biochemical normalization (week 30 faecal calprotectin [<250 µg/g], C-reactive protein [<5 mg/l]). Thresholds best associated with each outcome were evaluated in multivariate analyses. Results: Among patients with Crohn's disease, week 6 serum vedolizumab concentrations (>41.65 µg/ml) predicted normalization defined by C-reactive protein: Spearman correlation coefficient [ ρ ] = -0.26, P = 0.002 and multivariate analysis (MVA)-OR: 3.22, 95% CI: 1.32-7.87, P = 0.01, and at week 14 (>22.25 µg/ml): ρ = -0.38, P < 0.0001, and MVA-OR: 3.21, 95% CI: 1.26-8.17 but not faecal calprotectin. Similarly, among patients with ulcerative colitis, week 6 vedolizumab concentrations (>39.65 g/ml) predicted normalization defined by C-reactive protein: ρ = -0.26, P = 0.005 and MVA-OR: 4.03, 95% CI: 1.30-12.52, P = 0.016, and at week 14 (>17.35 µg/ml): ρ = -0.39, P = 0.0001 and MVA-OR: 6.95, 95% CI: 1.81-26.77, P = 0.005, but not faecal calprotectin. Conclusions: Induction and post-induction serum vedolizumab were not consistently associated with biochemical normalization. As such, proactive therapeutic drug monitoring for vedolizumab should not be routinely incorporated in a treat to target strategy for inflammatory bowel disease. Clinical Trial Registration Number: NCT04567628. Competing Interests: Cynthia H. Seow declares the following conflicts of interest: Janssen, AbbVie, Takeda, Lilly, Ferring, Shire, Pfizer, Sandoz, Pharmascience, Fresenius Kabi, and Amgen, Bristol Myers Squibb, ACHRI, CIHR, Calgary Health Trust, New South Wales Government Health. John K. Marshall declares the following conflicts of interest: AbbVie, Alimentiv, Amgen, AstraZeneca, Bausch Health, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, Lilly, Lupin, Organon, Pfizer, Pharmascience, Roche, Sandoz, Takeda, Teva, Viatris. Erin Stewart and Dr. Christopher Pettengell were employees at Pentavere Research Group Inc, Toronto, ON, Canada at the time of this study. Ryan Ward is an employee of Takeda Canada. Dr. Ryan Ward is not an owner of Takeda stock. Waqqas Afif declares the following conflicts of interest: Abbvie, Amgen, Bausch Health, Celtrion, Janssen, Merck, Novartis, Pfizer, Sanofi, Takeda. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)
Databáze:	MEDLINE
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