1. Nine controversial questions about augmentation therapy for alpha-1 antitrypsin deficiency: a viewpoint.
- Author
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Miravitlles M, Anzueto A, and Barrecheguren M
- Subjects
- Humans, Quality of Life, Treatment Outcome, alpha 1-Antitrypsin adverse effects, Lung diagnostic imaging, alpha 1-Antitrypsin Deficiency complications, alpha 1-Antitrypsin Deficiency diagnosis, alpha 1-Antitrypsin Deficiency drug therapy, Pulmonary Emphysema diagnosis, Pulmonary Emphysema drug therapy, Pulmonary Emphysema etiology, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Disease, Chronic Obstructive etiology
- Abstract
Augmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress.Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient., Competing Interests: Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi, Zambon and Grifols; and research grants from Grifols. A. Anzueto has received consultant fees from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Verona Pharma, TEVA and Mylan/Theravance. M. Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GSK and Boehringer Ingelheim; and consulting fees from GSK, Novartis, CSL Behring and Boehringer Ingelheim., (Copyright ©The authors 2023.)
- Published
- 2023
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