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Pharmacometric Analysis Linking Immunoglobulin Exposure to Clinical Efficacy Outcomes in Chronic Inflammatory Demyelinating Polyneuropathy
Tortorici MA, Yuraszeck T, Cornblath D, Bril V, Hartung HP, Sobue G, Lewis RA, Merkies ISJ, Lawo JP, Praus M, et al
CPT: pharmacometrics & systems pharmacology. 2021
Abstract
The two main objectives of this analysis were to (i) characterise the relationship between immunoglobulin (Ig) exposure and chronic inflammatory demyelinating polyneuropathy (CIDP) disease severity using data from 171 patients with CIDP who received either subcutaneous Ig (IgPro20; Hizentra®) or placebo (PATH study), and to (ii) simulate and compare exposure coverage with various dosing approaches considering weekly dosing to be the reference dose. IgG PK parameters including those from a previous population PK model were used to predict individual IgG profile and exposure metrics. Treatment-related changes in inflammatory neuropathy cause and treatment (INCAT) scores were best described by an E(max) model as a function of ΔIgG (total serum IgG at INCAT score assessment minus baseline IgG levels before intravenous Ig restabilisation). Simulations indicate that flexible dosing from daily to biweekly (every other week) provide an exposure coverage equivalent to that of a weekly Ig dose.