Assessment of Inhibitory Antibody Formation in Subjects with Hereditary Angioedema Treated with Plasma-Derived C1-Esterase Inhibitor Concentrate (Berinert®)
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Henriette Farkas, MD, PhD, DSc, Dumitru Moldovan, MD, PhD, Krystyna Obtułowicz, MD, T Shirov, MD, PhD, Jonathan M. Edelman, MD, Debora Williams-Herman, MD, Mikhail Rojavin, PhD

Limited data are available regarding C1-esterase inhibitor (C1-INH) administration and anti-C1-INH antibodies. This study assessed the incidence and relevance of antibody formation during treatment with pasteurized, nanofiltered plasma-derived C1-INH (pnfC1-INH; Berinert®/CSL Behring) in subjects with hereditary angioedema with C1-INH deficiency (C1-INH-HAE).


In this multicenter, open-label study, subjects with C1-INH-HAE (≥ 12 years of age) were given pnfC1-INH 20 IU/kg per HAE attack that required treatment and followed for 9 months. Blood samples were taken at baseline (day of first attack) and Months 3, 6, and 9 and analyzed for inhibitory (iC1-INHab) and non-inhibitory anti-C1-INH antibodies (niC1-INHab).


The study included 46 subjects (69.6% female; mean age, 38.9 y; all Caucasian) who received 221 on-site pnfC1-INH infusions; most subjects received ≤6 infusions. No subject tested positive (titer ≥1:50) for iC1-INHab at any time during the study. Thirteen (28.2%) subjects had detectable niC1-INHab in ≥1 sample. Nine (19.6%) subjects had detectable niC1-INHab at baseline; three of these had no detectable antibodies post-baseline. Of 10 (21.7%) subjects with ≥1 detectable result for niC1-INHab post-baseline, 6 had detectable niC1-INHab at baseline. Mean times to complete symptom resolution per subject and per attack were similar between the group of subjects who tested positive at any time for niC1-INHab and the group of subjects who consistently tested negative.  


Administration of pnfC1-INH was not associated with inhibitory anti-C1-INH antibody formation in this population. Non-inhibitory antibodies were detected in some patients but fluctuated during the study independently of pnfC1-INH administration and appeared to have no impact on pnfC1-INH efficacy.