Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database

Iris G M Schouten; Marise J Kasteleyn; Roula Tsonaka; Robert Bals; Alice C Turner; Ilaria Ferrarotti; Angelo G Corsico; Beatriz Lara; Marc Miravitlles; Robert A Stockley; Jan Stolk

doi:10.1183/23120541.00194-2021

Long-term effect of α₁-antitrypsin augmentation therapy on the decline of FEV₁ in deficient patients: an analysis of the AIR database

ERJ Open Res. 2021 Aug 23;7(3):00194-2021. doi: 10.1183/23120541.00194-2021. eCollection 2021 Jul.

Authors

Iris G M Schouten¹, Marise J Kasteleyn¹, Roula Tsonaka², Robert Bals^{3

4}, Alice C Turner⁵, Ilaria Ferrarotti^{6

4}, Angelo G Corsico^{6

4}, Beatriz Lara⁷, Marc Miravitlles^{8

4

9}, Robert A Stockley^{10

9}, Jan Stolk^{1

4

9}

Affiliations

¹ Dept of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
² Dept of Advanced Data Management and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands.
³ Dept of Pulmonology, Hospital of the University of the Saarland, Homburg, Germany.
⁴ These authors are member of the AATD Core Network of European Reference Network LUNG.
⁵ University of Birmingham, Institute of Applied Health Research, Edgbaston, UK.
⁶ Fondazione IRCCS Policlinico San Matteo, Centro Diagnosi AATD - Clinica Malattie Apparato Respiratorio, Pavia, Italy.
⁷ Dept of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.
⁸ Pneumology Dept, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain.
⁹ These authors contributed equally.
¹⁰ Lung Investigation Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

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 (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±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 FEV₁ 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 FEV₁ by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.