Abstract
Objectives
The randomized, double-blind, phase 2 b MUSE study evaluated the efficacy and safety of the type I interferon receptor antibody anifrolumab (300 mg or 1000 mg every 4 weeks) compared with placebo for 52 weeks in patients with chronic, moderate to severe SLE. Characterizing the exposure–response relationship of anifrolumab in MUSE will enable selection of its optimal dosage regimen in two phase 3 studies in patients with SLE.
Methods
The exposure–response relationship, pharmacokinetics (PK), and SLE Responder Index (SRI[4]) efficacy data were analysed using a population approach. A dropout hazard function was also incorporated into the SRI(4) model to describe the voluntary patient withdrawals during the 1-year treatment period.
Results
The population PK model found that type I IFN test–high patients, and patients with a higher body weight, had significantly greater clearance of anifrolumab. Stochastic clinical simulations demonstrated that doses <300 mg would lead to a greater-than-proportional reduction in drug exposure owing to type I interferon alpha receptor–mediated drug clearance (antigen-sink effect, more rapid drug clearance at lower concentrations) and suboptimal SRI(4) responses with wider confidence intervals.
Conclusions
Based on PK, efficacy, and safety considerations, anifrolumab 300 mg every 4 weeks was recommended as the optimal dosage for pivotal phase 3 studies in patients with SLE.
Exposure–Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma
