ALPHA-1 ANTITRYPSIN TREATMENT SLOWS EMPHYSEMA PROGRESSION INDEPENDENT OF BASELINE FEV1

Introduction: Patients with alpha-1 antitrypsin deficiency (AATD) develop pulmonary emphysema prematurely. RAPID, a randomized placebo-controlled trial, showed that treatment with A 1 -PI (Zemaira/Respreeza) slows emphysema progression. Based on observational data, which showed a reduced loss in forced expiratory volume in one second (FEV 1 ) in a subgroup of patients, current guidelines recommend treatment with A 1 -PI when FEV 1 is between 30 and 65% predicted. However, the relationship between the effect of treatment on lung structure preservation and FEV 1 is unclear. Aim: To assess the effect of treatment in relation to baseline FEV 1 % predicted as measured by change in computed tomography (CT) lung density in 180 patients randomized in RAPID with baseline FEV 1 between 27 and 79% predicted. Methods: Changes in annual CT lung density decline rates for both active and placebo treated patients were calculated at 2 years. A random coefficient effect model with baseline FEV1 and treatment group as covariates analyzed the influence on the treatment effect. Results: Baseline lung function impairment did not affect long-term changes in lung density (p=ns), whereas active treatment was associated with lung density preservation (P 1 % was flat with no interaction between treatment group and baseline FEV 1 . Discussion: These data demonstrate that patients with AATD who are treated with A 1 -PI therapy derive an equal benefit in terms of lung tissue preservation over 2-years that is independent of their pretreatment FEV 1 %.