Background: Since the recognition of alpha-1 antitrypsin deficiency (A1ATD) in 1963, interest in this condition has increased dramatically. A1ATD is now recognized as the only known genetic condition that leads to emphysema/chronic obstructive pulmonary disease (COPD) in many individuals with the condition. Augmentation therapy with plasma-derived alpha-1 antitrypsin (A1AT) was first introduced in 1987. OBJECTIVES AND SCOPE: To review current evidence on the efficacy, tolerability and biochemical composition of commercially available A1AT augmentation therapies. Literature was sought via electronic searching of bibliographic databases (MEDLINE) and other sources. No language or time period settings were applied. This is a narrative, descriptive review rather than a formal, systematic review.
Findings: Evidence of the therapeutic efficacy of A1AT augmentation therapy is beginning to accumulate, although further randomized, controlled trials are necessary. Clinical studies have reported reduced rates of lung function decline in COPD patients who received augmentation therapy, and significant benefit is seen in patients with forced expiratory volume in 1 second initially in the range of 35-49% of predicted normal. Augmentation therapy has also been shown to decrease the frequency of severe COPD exacerbations and to significantly increase survival rate. Biochemical studies have convincingly demonstrated that weekly intravenous infusion of each of the available plasma-derived A1AT preparations maintains serum A1AT levels above the putative protective threshold. Augmentation therapy with intravenous A1AT is generally well tolerated and long-term therapy in patients with severe A1ATD and pulmonary emphysema is feasible. Differences in the purification processes of available A1AT products are reflected in their relative purities and heterogeneities (abundance of A1AT isoforms), although the commercially available preparations are bioequivalent. Further studies are required to clarify whether variations in biochemical composition of purified A1AT are clinically important.
Conclusion: Intravenous augmentation therapy with A1AT currently represents the only viable and specific treatment option for patients with A1ATD.