%0 Journal Article %A Iris G.M. Schouten %A Marise J. Kasteleyn %A Roula Tsonaka %A Robert Bals %A Alice C. Turner %A Ilaria Ferrarotti %A Angelo G. Corsico %A Beatriz Lara %A Marc Miravitlles %A Robert A. Stockley %A Jan Stolk %T Long-term effect of alpha-1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database %D 2021 %R 10.1183/23120541.00194-2021 %J ERJ Open Research %P 00194-2021 %X Background Patients with ZZ (Glu342Lys) alpha-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with alpha-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years, failed to show a significant reduction of the annual decline of FEV1.Methods To compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, 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 was performed. The post-bronchodilator FEV1%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 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 a decline of −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).Conclusion In our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over an average period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: M. SchoutenConflict of interest: J. KasteleynConflict of interest: Roula TsonakaConflict of interest: Robert BalsConflict of interest: C. TurnerConflict of interest: Ilaria FerrarottiConflict of interest: G. CorsicoConflict of interest: Beatriz LaraConflict of interest: Dr. Miravitlles reports personal fees from CSL Behring, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from Chiesi, personal fees from GlaxoSmithKline, personal fees from Bial, personal fees from Gebro Pharma, personal fees from CSL Behring, personal fees from Laboratorios Esteve, personal fees from Ferrer, personal fees from Mereo Biopharma, personal fees from Verona Pharma, personal fees from Spin Therapeutics, personal fees from pH Pharma, personal fees from Novartis, personal fees from Sanofi, personal fees from Grifols, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from Cipla, personal fees from Menarini, personal fees from Rovi, personal fees from Bial, personal fees from Sandoz, personal fees from Zambon, personal fees from Novartis, personal fees from Grifols, during the conduct of the study.Conflict of interest: A. StockleyConflict of interest: Dr. Stolk reports personal fees from CSL Behring, personal fees from Kamada Ltd, during the conduct of the study; . %U https://openres.ersjournals.com/content/erjor/early/2021/06/25/23120541.00194-2021.full.pdf