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Replacement therapy for alpha-1-protease inhibitor deficiency in PiZ subjects with chronic obstructive lung disease
E W Schmidt1, B Rasche, W T Ulmer
1Bergmannsheil Hospital, Bochum, Federal Republic of Germany.
Insights
This study shows that weekly infusions of human-plasma-derived alpha-1-protease inhibitor (A1PI) are safe and feasible for patients with A1PI deficiency and chronic obstructive lung disease. The treatment maintained effective serum A1PI levels, suggesting potential for long-term replacement therapy.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Congenital alpha-1-protease inhibitor (A1PI) deficiency (PiZ phenotype) is linked to chronic obstructive lung disease (COPD).
- Replacement therapy with A1PI aims to restore protective serum levels and prevent lung damage.
Purpose of the Study:
- To assess the feasibility and safety of human-plasma-derived A1PI in patients with A1PI deficiency and COPD.
- To determine if a specific weekly dosage maintains therapeutic serum A1PI levels.
Main Methods:
- A six-month, multicenter feasibility and safety study involving 20 patients.
- Intravenous administration of human-plasma-derived A1PI at 60 mg/kg weekly.
- Measurement of serum A1PI concentrations, functional activity, and antibody development.
Main Results:
- Weekly A1PI infusions maintained serum levels above the protective threshold (35% of MZ phenotype levels).
- Infused A1PI remained largely in its active form in circulation.
- Adverse reactions were moderate and did not necessitate treatment changes; no hepatitis virus contamination or antibody development observed.
Conclusions:
- Human-plasma-derived A1PI replacement therapy appears safe and feasible for managing A1PI deficiency-related COPD.
- The study supports the potential efficacy of long-term A1PI augmentation therapy.
Abstract:
In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered intravenously, was shown to be sufficient to maintain patient serum levels above the threshold limit of 35 percent, the serum level of healthy persons of the MZ phenotype. This is supposed to be the minimal effective level for protection against the elastolytic attack of the lung and, therefore, satisfies one of the most important criteria of feasibility of long-term replacement therapy. The global concentration in serum or bronchiolar lavage fluid A1PI including active and inactivated A1PI was measured immunologically by rate nephelometry and radial immunodiffusion. The functional activity of A1PI, expressed as free inhibitor activity against trypsin and leukocyte elastase, confirmed that the infused A1PI remained mostly in its active form in the circulation. Reported adverse reactions were moderate and did not require alteration to the schedule of the infusions and/or the dose and rate of administration. Antibodies to A1PI as measured by the Ouchterlony method did not develop. Laboratory and physical signs of possible hepatitis virus contamination were not observed. The long-term replacement therapy, therefore, appears to be safe.