Science and Research

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

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.

  • Stolk, J.
  • Tov, N.
  • Chapman, K. R.
  • Fernandez, P.
  • MacNee, W.
  • Hopkinson, N. S.
  • Piitulainen, E.
  • Seersholm, N.
  • Vogelmeier, C. F.
  • Bals, R.
  • McElvaney, G.
  • Stockley, R. A.

Keywords

  • Administration, Inhalation
  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive/*complications
  • Severity of Illness Index
  • Treatment Outcome
  • Trypsin Inhibitors/*administration & dosage/adverse effects
  • alpha 1-Antitrypsin/*administration & dosage/adverse effects
  • alpha 1-Antitrypsin Deficiency/*complications/*drug therapy
  • Ltd, during the conduct of the study, and grants from CSL Behring, outside the
  • submitted work. Conflict of interest: N. Tov reports personal fees for consultancy
  • from Kamada Ltd, during the conduct of the study, and is an employee of Kamada Ltd,
  • outside the submitted work. Conflict of interest: K.R. Chapman reports personal fees
  • for consultancy from Kamada Ltd, during the conduct of the study, and grants from
  • CSL Behring and Grifols, outside the submitted work. Conflict of interest: P.
  • Fernandez reports consultancy fees from Kamada Ltd, during the planning, design,
  • conduct and reporting of the study. Conflict of interest: W. MacNee reports patient
  • recruitment fees from Kamada Ltd, during the conduct of the study
  • and grants and
  • personal fees from Pfizer and GlaxoSmithKline, and personal fees from Boehringer
  • Ingelheim, AstraZeneca, Novartis, Zambon and Chiesi, outside the submitted work.
  • Conflict of interest: N.S. Hopkinson has nothing to disclose. Conflict of interest:
  • E. Piitulainen has nothing to disclose. Conflict of interest: N. Seersholm has
  • nothing to disclose. Conflict of interest: C.F. Vogelmeier reports grants and
  • personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols and
  • Novartis, and personal fees from CSL Behring, Chiesi, Menarini, Mundipharma, Teva
  • and Cipla, outside the submitted work. Conflict of interest: R. Bals reports grants
  • from Kamada Ltd, during the conduct of the study
  • and grants from BMBF, DFG,
  • Schwiete Stiftung, Sander-Stiftung and Boehringer Ingelheim, and personal fees for
  • advisory board work and travel to meetings from GlaxoSmithKline, CSL Behring,
  • Boehringer Ingelheim, Grifols, AstraZeneca and Novartis, outside the submitted work.
  • Conflict of interest: G. McElvaney reports personal fees for advisory board work
  • from CSL Behring, grants and personal fees for advisory board work from Grifols, and
  • grants from Chiesi, outside the submitted work. Conflict of interest: R.A. Stockley
  • reports personal fees for advisory board membership from Kamada Ltd, during the
  • conduct of the study
  • personal fees for advisory board membership and lectures from
  • AstraZeneca, personal fees for advisory board membership from Medimmune, Almirall,
  • Baxter, Chiesi and Polyphor, personal fees for lectures from Nycomed and Takeda, and
  • personal fees for advisory board membership, lectures and travel to meetings from
  • Boehringer Ingelheim and CSL Behring, outside the submitted work.
Publication details
DOI: 10.1183/13993003.00673-2019
Journal: Eur Respir J
Number: 5
Work Type: Original
Location: UGMLC
Disease Area: COPD
Partner / Member: UMR
Access-Number: 31467115

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