Exposure-response relationships for the efficacy and safety of filgotinib and its metabolite GS-829845 in subjects with rheumatoid arthritis based on phase 2 and phase 3 studies.

ABSTRACT:

Aims

Filgotinib is a potent, oral, JAK1-preferential inhibitor for the treatment of rheumatoid arthritis (RA). This report describes exposure-response (ER) analyses of filgotinib for dose confirmation based on three phase 3 and two phase 2 studies in moderate to severe RA patients.

Methods

The pharmacokinetic exposures used in ER analyses were derived from population pharmacokinetic analysis. The exposure-efficacy relationships were assessed for efficacy endpoints (ACR20/50/70 and DAS28) over effective area under curve (AUC_eff ), the combined exposures of filgotinib and GS-829845 (major, active metabolite), with nonlinear logistic regression models developed. Also, a t-test was performed to compare the exposure between subjects who achieved response and those who

SUBMITTER: Meng A 

PROVIDER: S-EPMC9305466 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature