OBJECTIVES: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed genetic condition characterised by reduced level of alpha-1 antitrypsin enzyme which predisposes individuals to lung, liver, or other systemic diseases. Augmentation therapy (AT) is the only licensed treatment for patients with AATD associated lung diseases. The purpose of this study is to perform a systematic literature review (SLR) and meta-analysis of studies evaluating the safety and efficacy of approved AT in AATD.

METHODS: An SLR was conducted from database inception to May 2022 by searching three major biomedical databases to identify relevant randomized control trials (RCT) evaluating AT versus placebo in AATD patients. References of identified SLR/meta-analyses were investigated to identify additional studies. The SLR followed two review and a quality control process for screening and extractions. The risk of bias assessment was performed using Cochrane’s RoB-2 tool.

RESULTS: The SLR identified 9 RCTs assessing AT in AATD, of which only 3 RCTs were included in the meta-analysis. The RCTs contributing to meta-analysis varied regarding the trial duration, ranging from two to three years. ATs were associated with significantly better efficacy compared to placebo regarding the annual deterioration in lung density (random-effects, Sidik-Jonkman model, mean difference [MD]: 0.79; 95%CI: 0.29 to 1.28). The other analysed efficiency outcomes (annual FEV1% predicted and diffusing capacity of the lungs for carbon monoxide) were comparable (non-significant) between AT and placebo. In terms of safety outcomes i.e., any adverse events (AE), any serious AEs, and upper respiratory tract infections, the results of meta- analysis were also comparable between AT and placebo.

CONCLUSIONS: The SLR and meta-analysis highlight the favourable efficacy of AT for the treatment of AATD in terms of lung density, indicating reduction in emphysema progression. The evidence base for AT in AATD is scarce, hence, more studies examining AT are warranted for the treatment of adult patients with AATD.