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 (A1‐PI, Zemaira; CSL Behring) or placebo for 2 yrs. Eligible subjects (N=140) continued in Extension to receive A1‐PI for another 2 yrs. The Early‐Start (N=75) and Delayed‐Start (n=64) cohorts were defined by their treatment with A1‐PI and placebo in RAPID, respectively. Computed tomography (CT) lung density decline rate was measured annually and forced expiratory volume in 1 sec (FEV1) 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 A1‐PI. Changes in FEV1 Conclusions: In RAPID, A1‐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 A1‐PI therapy, suggesting that early treatment may reduce emphysema progression in AATD patients.over 4 yrs correlated significantly with changes in CT lung density.