Long-term effect of α<sub>1</sub>-antitrypsin augmentation therapy on the decline of FEV<sub>1</sub>in deficient patients: an analysis of the AIR database
Iris G. M. Schouten, Marise J. Kasteleyn, Roula Tsonaka, Robert Bals, Alice Turner, Ilaria Ferrarotti, Angelo Guido Corsico, Beatriz Lara, Marc Miravitlles, Robert A. Stockley, Jan Stolk
Abstract
Background Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV 1 ). Methods To compare the trajectory of FEV 1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV 1 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) was performed. The post-bronchodilator FEV 1 % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models. Results Data of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean± sd follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV 1 decline of −0.931% predicted per year (95% CI −1.144 to −0.718) in the untreated group and a decline of −1.016% predicted per year (95% CI −1.319 to −0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71). Conclusion In our study population, we could not detect a significant difference in the annual decline of FEV 1 by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.