Long-term effect of alpha-1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database
- Iris G.M. Schouten1,
- Marise J. Kasteleyn1,
- Roula Tsonaka2,
- Robert Bals3,10,
- Alice C. Turner4,
- Ilaria Ferrarotti5,10,
- Angelo G. Corsico5,10,
- Beatriz Lara6,
- Marc Miravitlles7,9,10,
- Robert A. Stockley8,9 and
- Jan Stolk1,9,10⇑
- 1Department of Pulmonology, Leiden University Medical Center, Leiden, NL
- 2Department of Advanced Data Management and Medical Statistics, Leiden University Medical Center, Leiden, NL
- 3Department of Pulmonology, Hospital of the University of the Saarland, Homburg, Germany
- 4University of Birmingham, Institute of Applied Health Research, Edgbaston, Birmingham, UK
- 5Fondazione IRCCS Policlinico San Matteo, Centro Diagnosi AATD - Clinica Malattie Apparato Respiratorio, Pavia, Italy
- 6Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- 7Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- 8Lung Investigation Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- 9These authors share last authorship
- 10These authors are member of the AATD Core Network of European Reference Network LUNG
- Jan Stolk (j.stolk{at}lumc.nl)
Abstract
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.
Footnotes
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Conflict of interest: M. Schouten
Conflict of interest: J. Kasteleyn
Conflict of interest: Roula Tsonaka
Conflict of interest: Robert Bals
Conflict of interest: C. Turner
Conflict of interest: Ilaria Ferrarotti
Conflict of interest: G. Corsico
Conflict of interest: Beatriz Lara
Conflict 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. Stockley
Conflict of interest: Dr. Stolk reports personal fees from CSL Behring, personal fees from Kamada Ltd, during the conduct of the study; .
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- Received March 17, 2021.
- Accepted June 21, 2021.
- Copyright ©The authors 2021
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