Reduction of severe exacerbations and hospitalization-derived costs in alpha-1-antitrypsin-deficient patients treated with alpha-1-antitrypsin augmentation therapy

Abstract

the investigators of the rEXA study group Abstract: Objective: Severe exacerbations in alpha-1-antitrypsin (AAT)-deficient patients with chronic obstructive pulmonary disease (COPD) and/or emphysema are a major cause of hospitalization. A multicentre, observational, retrospective study was undertaken to evaluate the effect of continuous AAT augmentation therapy in reducing the incidence of exacerbations in these patients. Methods: Patients treated with Trypsone ® or Prolastin ® for at least 18 months were recruited if their medical records for 18 months before starting augmentation therapy were available. The number of mild and severe exacerbations in the two periods was compared and hospitalization-related costs were analysed. Results: A total of 127 patients were recruited; 75 of them experienced at least one exacerbation in the period prior to augmentation. In the treatment period, the mean number of exacerbations per patient was reduced in both the total population and the population with exacerbations (mean ± SD: 1.2 ± 1.6 versus 1.0 ± 2.2 and 2.0 ± 1.6 versus 1.4 ± 2.7, respectively; p < 0.01). The percentage of patients experiencing exacerbations was reduced in the total population (59.1% versus 44.1%; p < 0.05). In the patient subgroup of the total population who experienced a change in their number of exacerbations between the two periods, 43.7% had a reduction and 21.4% had an increase (p < 0.01). The number of severe exacerbations diminished in 42.9% of this subgroup and increased in 12.0% (p < 0.001). Most adverse events were nonserious or not related to treatment. Hospitalization costs savings per patient associated with treatment ranged from approximately €400 to €900 (p < 0.05). Conclusions: Augmentation therapy with AAT concentrates was associated with a reduction in the incidence and severity of exacerbations in AAT-deficient patients, which resulted in lower hospitalization expenditures.

Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review

“…The most recent study by Barros-Tizon et al37 was a retrospective medical records review of 127 participants evaluating the effect of augmentation on exacerbation rate. Seventy-five patients had ≥1 exacerbation during the 18 months follow-up required prior to commencement of augmentation.…”

“…Meta-analysis also revealed a small but significant increase in annual exacerbation rate on augmentation. This is somewhat counterintuitive and contradicted by studies included in narrative synthesis, which either showed a benefit or no significant difference in exacerbation rate or severity 17,37,54. Increased contact with health care professionals, simply due to attending for infusions, could lead to increased reporting of exacerbations, but this is the opposite result from published observational studies.…”

“…This has been beneficial in usual COPD trials83,84 as it avoids recall bias and gives accurate data on severity and duration; hence, the results will be of interest. The Spanish study that focused on exacerbations had issues with missing data and also used variable treatment regimens, such that bias and lack of comparability to RCTs are an issue 37. There are several other reasons why the exacerbations result should be viewed with caution; first, prestudy exacerbation frequency was not reported in the three RCTs.…”

Long-term experience in the treatment of α1-antitrypsin deficiency: 25 years of augmentation therapy

“…Limited evidence supports the hypothesis that AAT augmentation therapy reduces the incidence of lung infections in addition to slowing the deterioration of lung function and leading to decreased mortality [13,[17][18][19].…”

“…A recent multicentre, retrospective observational study in 127 severe AATD patients with chronic obstructive pulmonary disease (COPD) demonstrated that augmentation therapy with AAT concentrates (Prolastin or Trypsone) for at least 18 months was associated with a reduced incidence and severity of exacerbations, which subsequently resulted in significant hospitalisation cost savings [18].…”