Meta-analysis of Vedolizumab trough levels as a correlate of remission in patients with inflammatory bowel diseases

Details

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Version: After imprimatur
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Serval ID
serval:BIB_AB6FAAFF7849
Type
A Master's thesis.
Publication sub-type
Master (thesis) (master)
Collection
Publications
Institution
Title
Meta-analysis of Vedolizumab trough levels as a correlate of remission in patients with inflammatory bowel diseases
Author(s)
ALIBRANDO L.
Director(s)
PERREAU M.
Codirector(s)
MASTRANGELO A.
Institution details
Université de Lausanne, Faculté de biologie et médecine
Publication state
Accepted
Issued date
2022
Language
english
Number of pages
39
Abstract
Context
Inflammatory bowel disease (IBD) encompasses Crohn's Disease (CD) and Ulcerative Colitis (UC). Several treatments have been introduced to control the inflammatory processes, including immunosuppressive drugs and biological therapies. These last have become one of the mainstays of IBD management. Nevertheless, some patients may experience therapeutic failures to biological therapies, as a consequence of anti-drug antibodies development and/or insufficient drug concentration. Dose adjustment based on monitoring of drug trough levels has improved the management of patients not responding to anti-TNF-α. Vedolizumab is a humanized monoclonal antibody targeting the integrin α4β7. However, to date, Vedolizumab trough level associated with disease remission is not available.
Research question
The objective of this study is to exploit the existing literature to determine a therapeutic trough level for Vedolizumab associated with response to treatment in IBD. Such a therapeutic trough level could be potentially used in daily clinical practice to guide and adapt the medication dosing according to a concentration threshold.
Methods
This study is a meta-analysis based on retrospective studies fulfilling some selection criteria. These last included: treatment with Vedolizumab in IBD, treatment response measure expressed as a dichotomous outcome (response vs. not-response), and a Vedolizumab trough level associated with treatment response. To reduce the heterogeneity between studies, our database explored separately the association between Vedolizumab trough levels and response to treatment in the two diseases (CD and UC), for two response outcomes (endoscopic and clinical remission) and in two phases after Vedolizumab initiation (induction and maintenance). Vedolizumab trough levels and the proportion of patients in remission vs. no-remission, for each mentioned case, were collected and used to perform meta-analysis and meta-ROC.
Results
Through our analysis, we determined that patients in clinical or endoscopic remission, in both diseases, showed a higher trough level of Vedolizumab at week 6 or 22 than patients who did not achieve remission, suggesting an association between the trough levels of Vedolizumab and favorable outcomes. We investigated by Meta-ROC curves whether we could identify a target cut-off level of plasmatic Vedolizumab that could be used to differentiate patients achieving clinical or endoscopic response. Our analysis identified Vedolizumab cut-off trough levels associated to favorable outcomes in both UC and CD. However, heterogeneity between studies was consistent, and no definitive conclusion could be drawn.
Conclusion
In conclusion, our meta-analysis identified an association between increased Vedolizumab trough levels and clinical and endoscopic remission in patients with IBDs. However, due to a significant heterogeneity of the selected studies, we were not able to identify a precise threshold for Vedolizumab that could be used in clinical practice.
Keywords
Crohn disease, Ulcerative Colitis, Vedolizumab, trough level, meta-analysis
Create date
12/09/2023 14:26
Last modification date
19/10/2023 6:12
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