Use of a C1 Inhibitor Concentrate in Adults ≥65 Years of Age with Hereditary Angioedema: Findings from the International Berinert® (C1-INH) Registry

Anette Bygum, Inmaculada Martinez-Saguer, Murat Bas, Jeffrey Rosch, Jonathan Edelman, Mikhail Rojavin, Debora Williams-Herman, Berinert Registry Investigators, Anette Bygum, Inmaculada Martinez-Saguer, Murat Bas, Jeffrey Rosch, Jonathan Edelman, Mikhail Rojavin, Debora Williams-Herman, Berinert Registry Investigators

Abstract

Background: Treatment of hereditary angioedema (HAE) in 'older adults' (those aged ≥65 years) has not been well studied. The international Berinert Patient Registry collected data on the use of intravenous plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert®/CSL Behring) in patients of any age, including many older adults.

Methods: This observational registry, conducted from 2010 to 2014 at 30 US and seven European sites, gathered prospective (post-enrollment) and retrospective (pre-enrollment) usage and adverse event (AE) data on subjects treated with pnfC1-INH.

Results: The registry documented 1701 pnfC1-INH infusions in 27 older adults. A total of 1511 HAE attacks treated with pnfC1-INH administration were reported among 25 of the 27 (92.6 %) older adults. Among the older adults, mean (standard deviation [SD]) (8.8 [4.1] IU/kg) and median (6.4 IU/kg) pnfC1-INH doses were lower than those reported for 252 'younger adults' (those aged <65 years: 12.9 [6.2], 12.5 IU/kg, respectively). A total of 19 AEs occurred in 8 of 23 (34.8 %) older adults with prospective data, for rates of 0.83 events per subject and 0.02 events per infusion, similar to corresponding rates in younger adults (0.91 and 0.03, respectively). None of the AEs were considered related to pnfC1-INH, and all but two events (prostatectomy, gastrointestinal bleeding) were mild or moderate in severity. Administration of pnfC1-INH outside of a healthcare setting was reported for 1609 infusions in 16 older adults, representing 94.6 % of all pnfC1-INH infusions in this age group. There were no recorded instances of difficulty with self-administration of intravenous pnfC1-INH.

Conclusions: These findings suggest a high degree of safety with intravenous pnfC1-INH use in older adults with HAE, regardless of administration setting. Trial Registration Clinicaltrials.gov NCT01108848.

Conflict of interest statement

Compliance with Ethical Standards Funding This study was funded by CSL Behring. Disclosures Dr. Anette Bygum has received consulting fees and travel expenses from CSL Behring and Shire; grants and writing assistance from CSL Behring; fees for participation in reviews and speaker fees as a chairperson for Shire; she has taken an unpaid part in educational events with SOBI; and has provided unpaid writing assistance for ViroPharma. Dr. Inmaculada Martinez-Saguer has received consultancy fees and fees for participation in reviews from CSL Behring, Shire, Sobi, BioCryst, and Pharming. Dr. Murat Bas has received grants, consulting fees, honorarium, and travel support from CSL Behring. Dr. Jeffrey Rosch has no conflicts to disclose. Drs Jonathan Edelman and Mikhail Rojavin are employees at CSL Behring. Dr. Debora Williams-Herman was an employee of CSL Behring at the time of study conduct.

Figures

Fig. 1
Fig. 1
Hereditary angioedema attack* patterns by anatomic location for subjects aged ≥65 years compared with those for subjects aged 17 to a Percentage of subjects experiencing at least one attack per anatomic location. Percentages are based on the number of subjects with at least one attack. Subjects were included only one time for each anatomic location for which they experienced at least one attack. Anatomic location data were missing for seven subjects aged ≥65 years and 54 subjects aged 17 to <65 years. b Percentage of all reported attacks* by anatomic location. Anatomic location data were missing for 589 (39.0 %) of attacks in subjects aged ≥65 years and 1211 (12.6 %) of attacks in subjects aged 17 to <65 years. *Only attacks treated with pnfC1-INH (Berinert). HAE hereditary angioedema
Fig. 2
Fig. 2
Severity of hereditary angioedema attacks*. a Per subject (highest intensity reported) and b per attack among subjects aged ≥65 years compared with subjects aged 17 to <65 years. a Per subject†, highest intensity reported. Attack density ratings were not available in three (1.2 %) subjects aged 17 to <65 years. b Severity distribution of all recorded attacks*. Attack intensity ratings were not available for 280 (18.5 %) of attacks in subjects aged ≥65 years and 1267 (13.2 %) of attacks in subjects aged 17 to <65 years. *Only attacks treated with pnfC1-INH (Berinert). †For per subject reporting of attack intensity, each subject is included in only one category based on the maximum intensity attack

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