Quantitative disease progression model of α-1 proteinase inhibitor therapy on computed tomography lung density in patients with α-1 antitrypsin deficiency.

ABSTRACT:

Aims

Early-onset emphysema attributed to α-1 antitrypsin deficiency (AATD) is frequently overlooked and undertreated. RAPID-RCT/RAPID-OLE, the largest clinical trials of purified human α-1 proteinase inhibitor (A₁ -PI; 60 mg kg^-1  week^-1 ) therapy completed to date, demonstrated for the first time that A₁ -PI is clinically effective in slowing lung tissue loss in AATD. A posthoc pharmacometric analysis was undertaken to further explore dose, exposure and response.

Methods

A disease progression model was constructed, utilizing observed A₁ -PI exposure and lung density decline rates (measured by computed tomography) from RAPID-RCT/RAPID-OLE, to predict effects of population variability and higher doses on A₁ -PI

SUBMITTER: Tortorici MA 

PROVIDER: S-EPMC5651313 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature