LATE-BREAKING ABSTRACT: Long-term efficacy of A1-PI therapy in RAPID and RAPID extension trials

Introduction: RAPID (NCT00261833), the largest (N=180) randomized placebo-controlled trial assessing emphysema progression in alpha-1 antitrypsin deficiency (AATD) completed to date, was followed by the open-label RAPID Extension trial (NCT00670007). Methods: Subjects in RAPID received alpha-1 proteinase inhibitor (A 1 -PI, Zemaira; CSL Behring) or placebo for 2 yrs. Eligible subjects (N=140) continued in Extension to receive A 1 -PI for another 2 yrs. The Early-Start (N=75) and Delayed-Start (n=64) cohorts were defined by their treatment with A 1 -PI and placebo in RAPID, respectively. Computed tomography (CT) lung density decline rate was measured annually and forced expiratory volume in 1 sec (FEV 1 ) was measured quarterly. Results: Annual CT lung density decline rate in the first 2 yrs was less by 0.75 g/L/yr in the Early-Start cohort (-1.51 g/L/yr vs -2.26 g/L/yr, p=0.021 one sided). In the Delayed-Start cohort, lung density decline was reduced to -1.26 g/L/yr after switching to A 1 -PI. Changes in FEV 1 over 4 yrs correlated significantly with changes in CT lung Conclusions: In RAPID, A 1 -PI therapy reduced the rate of lung density decline compared to placebo. Over 48 months, the Delayed-Start cohort showed a greater loss of lung density. These data demonstrate a disease-modifying effect of A 1 -PI therapy, suggesting that early treatment may reduce emphysema progression in AATD patients.