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Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD

Stolk, Jan ; Tov, Naveh ; Chapman, Kenneth R. ; Fernandez, Pablo ; MacNee, William ; Hopkinson, Nicholas S. ; Piitulainen, Eeva LU ; Seersholm, Niels ; Vogelmeier, Claus F. and Bals, Robert , et al. (2019) In European Respiratory Journal 54(5).
Abstract

Patients with inherited α1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently experience exacerbations. We postulated that inhalation of nebulised AAT would be an effective treatment. We randomly assigned 168 patients to receive twice-daily inhalations of 80 mg AAT solution or placebo for 50 weeks. Patients used an electronic diary to capture exacerbations. The primary endpoint was time from randomisation to the first event-based exacerbation. Secondary endpoints included change in the nature of the exacerbation as defined by the Anthonisen criteria. Safety was also assessed. Time to first moderate or severe exacerbation was a median of 112 days (interquartile range (IQR) 40-211... (More)

Patients with inherited α1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently experience exacerbations. We postulated that inhalation of nebulised AAT would be an effective treatment. We randomly assigned 168 patients to receive twice-daily inhalations of 80 mg AAT solution or placebo for 50 weeks. Patients used an electronic diary to capture exacerbations. The primary endpoint was time from randomisation to the first event-based exacerbation. Secondary endpoints included change in the nature of the exacerbation as defined by the Anthonisen criteria. Safety was also assessed. Time to first moderate or severe exacerbation was a median of 112 days (interquartile range (IQR) 40-211 days) for AAT and 140 days (IQR 72-142 days) for placebo (p=0.0952). The mean yearly rate of all exacerbations was 3.12 in the AAT-treated group and 2.67 in the placebo group ( p=0.31). More patients receiving AAT reported treatment-related treatment-emergent adverse events compared to placebo (57.5% versus 46.9%, respectively) and they were more likely to withdraw from the study. After the first year of the study, when modifications to the handling of the nebuliser were introduced, the rate of safety events in the AAT-treated group dropped to that of the placebo group. We conclude that in AATD patients with severe COPD and frequent exacerbations, AAT inhalation for 50 weeks showed no effect on time to first exacerbation but may have changed the pattern of the episodes.

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Contribution to journal
publication status
published
subject
in
European Respiratory Journal
volume
54
issue
5
article number
1900673
publisher
European Respiratory Society
external identifiers
  • scopus:85075812804
  • pmid:31467115
ISSN
0903-1936
DOI
10.1183/13993003.00673-2019
language
English
LU publication?
yes
id
c95ba987-163a-4314-aacb-93776252b105
date added to LUP
2019-12-18 09:49:54
date last changed
2021-06-16 02:58:11
@article{c95ba987-163a-4314-aacb-93776252b105,
  abstract     = {<p>Patients with inherited α1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently experience exacerbations. We postulated that inhalation of nebulised AAT would be an effective treatment. We randomly assigned 168 patients to receive twice-daily inhalations of 80 mg AAT solution or placebo for 50 weeks. Patients used an electronic diary to capture exacerbations. The primary endpoint was time from randomisation to the first event-based exacerbation. Secondary endpoints included change in the nature of the exacerbation as defined by the Anthonisen criteria. Safety was also assessed. Time to first moderate or severe exacerbation was a median of 112 days (interquartile range (IQR) 40-211 days) for AAT and 140 days (IQR 72-142 days) for placebo (p=0.0952). The mean yearly rate of all exacerbations was 3.12 in the AAT-treated group and 2.67 in the placebo group ( p=0.31). More patients receiving AAT reported treatment-related treatment-emergent adverse events compared to placebo (57.5% versus 46.9%, respectively) and they were more likely to withdraw from the study. After the first year of the study, when modifications to the handling of the nebuliser were introduced, the rate of safety events in the AAT-treated group dropped to that of the placebo group. We conclude that in AATD patients with severe COPD and frequent exacerbations, AAT inhalation for 50 weeks showed no effect on time to first exacerbation but may have changed the pattern of the episodes.</p>},
  author       = {Stolk, Jan and Tov, Naveh and Chapman, Kenneth R. and Fernandez, Pablo and MacNee, William and Hopkinson, Nicholas S. and Piitulainen, Eeva and Seersholm, Niels and Vogelmeier, Claus F. and Bals, Robert and McElvaney, Gerry and Stockley, Robert A.},
  issn         = {0903-1936},
  language     = {eng},
  month        = {11},
  number       = {5},
  publisher    = {European Respiratory Society},
  series       = {European Respiratory Journal},
  title        = {Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD},
  url          = {http://dx.doi.org/10.1183/13993003.00673-2019},
  doi          = {10.1183/13993003.00673-2019},
  volume       = {54},
  year         = {2019},
}