Therapeutic drug monitoring of vedolizumab therapy in inflammatory bowel disease.

Autor: Steenholdt C; Department of Gastroenterology, Herlev and Gentofte Hospital, Herlev, Denmark., Lorentsen RD; Department of Gastroenterology, Herlev and Gentofte Hospital, Herlev, Denmark., Petersen PN; Department of Gastroenterology, Herlev and Gentofte Hospital, Herlev, Denmark., Widigson ES; Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität, Berlin, Germany.; Graduate Research Training Program PharMetrX, Berlin, Germany., Kloft C; Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität, Berlin, Germany., Klaasen RA; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway., Brynskov J; Department of Gastroenterology, Herlev and Gentofte Hospital, Herlev, Denmark.
Jazyk: angličtina
Zdroj: Journal of gastroenterology and hepatology [J Gastroenterol Hepatol] 2024 Jun; Vol. 39 (6), pp. 1088-1098. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1111/jgh.16518
Abstrakt: Background: Therapeutic drug monitoring is effective for optimizing anti-tumor necrosis factor therapies in inflammatory bowel disease, but for vedolizumab, a gut-selective leucocyte migration inhibitor, data are scarce.
Methods: Observational cohort study including 116 bio-experienced inflammatory bowel disease patients treated with vedolizumab for active luminal disease. Biobanked trough blood samples (n = 676) covering 96% of patients were analyzed using a drug-binding immunofluorometric assay. Steroid-free treatment outcomes were classified by clinical disease activity indices and objective findings, primarily endoscopy.
Results: Patients with clinical remission to vedolizumab induction therapy (37%) had significantly higher trough levels than those without at weeks 6 (mean 34.1 vs 28.0 μg/mL, P = 0.03) and 10 (34.8 vs 27.5 μg/mL, P = 0.01). Optimal thresholds for discrimination were 32.4 μg/mL (AUC ROC 0.66, P = 0.04) and 23.5 (AUC ROC 0.67, P = 0.01), respectively. This positive association persisted during maintenance phase with 11.9 μg/mL (AUC ROC 0.69, P < 0.01) associated with clinical remission (37%) and 15.3 (AUC ROC 0.74, P < 0.001) for objective remission (46%). Stratification by temporal evolution of treatment effects revealed higher induction and maintenance vedolizumab levels in persistent and slow responders as compared to secondary or persistent failures. Pharmacokinetics was influenced by rare formation of anti-vedolizumab antibodies (2%), and to a lesser extent gender and albumin during induction, but not disease severity, concomitant steroids, or thiopurine metabolites. Switching to subcutaneous administrations resulted in 2.3-fold increase in steady-state trough levels.
Conclusion: Our study supports maintaining adequate drug exposure being essential for sustained positive outcomes of vedolizumab and emphasizes individualized, therapeutic drug monitoring-based treatment regimens. Controlled trials and pharmacokinetic modeling are, however, needed.
(© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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