Long-term effect of alpha-1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients

Abstract

<b>Background:</b> Patients with ZZ (Glu342Lys) alpha-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with alpha-1-antitrypsin (AAT) in randomized controlled trials over 2-3 years, failed to show a significant reduction of the annual decline of the forced expiration volume in one second (FEV₁). <b>Aim and objectives:</b> To compare the trajectory of FEV₁ change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving augmentation therapy <b>Methods:</b> A retrospective analysis of FEV₁ values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries: Germany, UK, Spain, Italy and The Netherlands. The post-bronchodilator FEV₁ % predicted values for baseline and follow-up over time from patients receiving or not receiving augmentation therapy were analysed in linear mixed effects models. <b>Results:</b> In total 374 patients were analysed: 246 untreated and 128 treated with regular intravenous AAT augmentation therapy. The mean follow-up duration of the untreated group was 8.60 (SD ± 3.34) years and 8.59 (± 2.62) years for the treated group. The mixed effects model analysis showed a mean FEV₁ decline of -0.931% predicted per year (95% confidence interval -1.144 to -0.718) in the untreated group and -1.016 % predicted per year (-1.319 to -0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p = 0.71). <b>Conclusion:</b> In our study population, we could not detect significant differences in the annual decline of FEV₁ with AAT augmentation treatment over an average period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.