A review of augmentation therapy for alpha-1 antitrypsin deficiency

Expert Opin Biol Ther. 2012 Jun;12(6):685-700. doi: 10.1517/14712598.2012.676638. Epub 2012 Apr 14.

Abstract

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a relatively common, but under-recognized condition which manifests commonly with liver cirrhosis and emphysema. Specific therapy for lung-affected individuals with AATD is augmentation therapy, which consists of intravenous infusion of purified human plasma-derived alpha-1 antitrypsin (AAT). Augmentation therapy was first approved by the United States Food and Drug Administration (FDA) in 1987 for emphysema associated with severe AATD and today, six augmentation therapy preparations, all of which derive from pooled human plasma, have received FDA approval.

Areas covered: This paper reviews augmentation therapy for AATD, including the various available commercial preparations, their processing and biochemical differences, evidence regarding biochemical and clinical efficacy, patterns of clinical use, adverse effect profiles, cost-effectiveness and potential uses in conditions other than emphysema associated with AATD. Novel and emerging strategies for treating AATD are briefly discussed next, including alternative dosing and administration strategies, recombinant preparations, small molecule inhibitors of neutrophil elastase and of AAT polymerization, autophagy-enhancing drugs and gene therapy approaches.

Expert opinion: We conclude with a discussion of our approach to managing patients with AATD and use of augmentation therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cost-Benefit Analysis
  • Drug Costs
  • Enzyme Replacement Therapy* / adverse effects
  • Enzyme Replacement Therapy* / economics
  • Genetic Therapy
  • Humans
  • Infusions, Intravenous
  • Leukocyte Elastase / antagonists & inhibitors
  • Leukocyte Elastase / metabolism
  • Protease Inhibitors / therapeutic use
  • Recombinant Proteins / administration & dosage
  • Treatment Outcome
  • alpha 1-Antitrypsin / administration & dosage*
  • alpha 1-Antitrypsin / adverse effects
  • alpha 1-Antitrypsin / economics
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin Deficiency / economics
  • alpha 1-Antitrypsin Deficiency / enzymology
  • alpha 1-Antitrypsin Deficiency / genetics
  • alpha 1-Antitrypsin Deficiency / therapy*

Substances

  • Protease Inhibitors
  • Recombinant Proteins
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin
  • Leukocyte Elastase