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- Title
Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Anifrolumab.
- Authors
Tang, Weifeng; Tummala, Raj; Almquist, Joachim; Hwang, Michael; White, Wendy I.; Boulton, David W.; MacDonald, Alexander
- Abstract
The type I interferon (IFN) signaling pathway is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Anifrolumab is a monoclonal antibody that targets the type I IFN receptor subunit 1. Anifrolumab is approved in several countries for patients with moderate to severe SLE receiving standard therapy. The approved dosing regimen of anifrolumab is a 300-mg dose administered intravenously every 4 weeks; this was initially based on the results of the Phase 2b MUSE and further confirmed in the Phase 3 TULIP-1 and TULIP-2 trials, in which anifrolumab 300-mg treatment was associated with clinically meaningful improvements in disease activity with an acceptable safety profile. There have been several published analyses of the pharmacokinetic and pharmacodynamic profile of anifrolumab, including a population–pharmacokinetic analysis of 5 clinical studies of healthy volunteers and patients with SLE, in which body weight and type I IFN gene expression were significant covariates identified for anifrolumab exposure and clearance. Additionally, the pooled Phase 3 SLE population has been used to evaluate how serum exposure may be related to clinical responses, safety risks, and pharmacodynamic effects of the 21-gene type I IFN gene signature (21-IFNGS). The relevance of 21-IFNGS with regard to clinical efficacy outcomes has also been analyzed. Herein, the clinical pharmacokinetics, pharmacodynamics, and immunogenicity of anifrolumab as well as results of population–pharmacokinetics and exposure–response analyses are reviewed.
- Subjects
IMMUNE response; PHARMACODYNAMICS; TYPE I interferons; PHARMACOKINETICS; INTERFERON receptors; SYSTEMIC lupus erythematosus
- Publication
Clinical Pharmacokinetics, 2023, Vol 62, Issue 5, p655
- ISSN
0312-5963
- Publication type
Article
- DOI
10.1007/s40262-023-01238-2