PURPOSE: To review the safety and tolerability of an alpha1-proteinase inhibitor (A1-PI) augmentation therapy, Zemaira® (CSL Behring) [Z(A1-PI)].
METHODS: Safety and tolerability data from four clinical studies of Z(A1-PI), including 2 single-dose (Studies 1 and 2) and 2 multiple-dose investigations (Studies 3 and 4), were retrospectively collated. Assessments included patient baseline characteristics, extent of exposure to Z(A1-PI), adverse events (AEs) including number, whether serious or non-serious, severity (mild, moderate, severe), and relationship of AE to Z(A1-PI) treatment.
RESULTS: In total, 89 patients (59M, 30F), median age 49 y (range: 37–68) received Z(A1-PI) in four studies. The mean baseline serum A1-PI level was 5.6 μM (SD 1.5). Seventy-six of 89 patients received the recommended dose of Z(A1-PI) 60 mg/kg during the four studies, representing a total of 1283 infusions (1296 for all doses). In addition, 32 patients received a control preparation of A1-PI (Talecris Biotherapeutics) in Studies 2 and 4; a total of 160 infusions. A total of 298 AEs were reported for the 1296 infusions of Z(A1-PI) [0.230 AEs per infusion]. Five patients experienced a total of 6 AEs related to Z(A1-PI) including injection site pain, paresthesia, asthenia, dizziness, pruritus and headache. All were considered to be mild (0.005 related AEs per infusion). None of the AEs was rated as serious. A total of 83 AEs were reported for the 160 infusions of control A1-PI preparation (0.519 AEs per infusion), of which 5 AEs were considered to be treatment related (0.031 related AEs per infusion).
CONCLUSION: Pooled data from four clinical studies indicate that Z(A1-PI) is safe and well tolerated.
CLINICAL IMPLICATIONS: Z(A1-PI) has been commercially available since 2003. This is the first report of an assessment of safety using data pooled from four clinical studies. Current knowledge of the safety and tolerability profile of Z(A1-PI) is consistent with the results of this analysis.
DISCLOSURE: Garrett Bergman, No Product/Research Disclosure Information; Employee The authors are employees of CSL Behring.