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Exposure–efficacy and exposure–safety analyses of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera.

Authors :
Qin, Albert
Wu, Daoxiang
Li, Yaning
Zhang, Jingjing
Wang, Wei
Shen, Weihong
Liao, Jason
Lin, Sheena
Chang, Cynthia
Chen, Haoqi
Cui, Jie
Su, Xia
Source :
British Journal of Clinical Pharmacology. Jun2024, Vol. 90 Issue 6, p1493-1502. 10p.
Publication Year :
2024

Abstract

Aims: To investigate the exposure–response (E‐R) relationship, including exposure–efficacy and exposure–safety, of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera (PV). Methods: Based on the results of the phase II trial A20‐202 regarding ropeginterferon alfa‐2b in patients with PV, E‐R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E‐R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa‐2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment‐related adverse events (TRAEs). Results: A clear relationship between the exposure to ropeginterferon alfa‐2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure–JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa‐2b and baseline body surface area. Exposure–safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. Conclusions: Our analyses have shown that patients with PV treated with ropeginterferon alfa‐2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250–350–500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa‐2b for PV treatment in China. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03065251
Volume :
90
Issue :
6
Database :
Academic Search Index
Journal :
British Journal of Clinical Pharmacology
Publication Type :
Academic Journal
Accession number :
177562727
Full Text :
https://doi.org/10.1111/bcp.16043