Objective: To analyze the immuno-safety of rhC1INH in symptomatic patients with HAE.
Methods: Plasma samples were collected pre-treatment and 22 and 90 days post-treatment of an acute angioedema attack. Plasma samples were tested for the presence of antibodies against plasma-derived C1INH and rhC1INH using six different, validated enzyme-linked immunosorbent assays (ELISAs), to detect IgM, IgG and IgA antibodies against plasma-derived C1INH or rhC1INH. Antibodies against HRI in plasma samples were measured in an ELISA testing for all antibody classes. Plasma samples from normal healthy controls and HAE patients, never exposed to rhC1INH, were used to estimate cut off levels of the assays. Plasma samples with antibody levels above the cut-off level in the screening assays were tested in confirmatory displacement assay in case of anti-HRI antibodies and in an assay for neutralizing antibodies in case of antibodies against C1INH
Results: Data from 155 symptomatic HAE patients having received a total of 424 administrations of rhC1INH were analyzed. The frequency of anti-C1INH antibody levels above the assay cut-off was low and similar in pre- and post-exposure samples (1.7% and 1.8%, respectively). Results above the assay cut-off were sporadic and transient. Occurrence of anti-C1INH antibodies did not correlate with repeated treatment or time since last treatment. No neutralizing antibodies were detected. A total of 5/155 (3%) rhC1INH-treated patients had confirmed anti-HRI antibodies; these included 1 patient with presence of anti-HRI antibodies prior to exposure to rhC1INH. The presence of anti-C1INH and anti-HRI antibodies was not associated with clinical symptoms. The presence of anti-C1INH antibodies did not affect clinical efficacy.
Conclusions: rhC1INH used for the treatment of acute HAE attacks has a low potential to induce antibodies and has a reassuring immuno-safety profile.