Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Anifrolumab.

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.

• Authors: Weifeng Tang, Raj Tummala, Joachim Almquist, Michael Hwang, Wendy I White, David W Boulton, Alexander MacDonald
• Journal: Clinical pharmacokinetics (Clin Pharmacokinet) Vol. 62 Issue 5 Pg. 655-671 (05 2023) ISSN: 1179-1926 [Electronic] Switzerland
• PMID: 37148484 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• anifrolumab
• Antibodies, Monoclonal, Humanized
• Antibodies, Monoclonal

Topics

• Humans
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Lupus Erythematosus, Systemic (drug therapy)
• Treatment Outcome