453 A 26-Year Review of Long-term Safety of a Human Pasteurized C1 Inhibitor Concentrate

BACKGROUND: Hereditary angioedema (HAE) is a rare disorder characterized by C1 inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema. C1-INH replacement therapy is recommended as first-line therapy for treatment of acute HAE attacks, demonstrating rapid onset of symptom relief within 30 minutes or less. CSL Behring's human pasteurized C1-INH concentrate has been marketed since 1985 for the treatment of acute HAE attacks in Germany and numerous other countries. METHODS: We reviewed spontaneous reports of adverse drug reactions (ADRs) received by CSL Behring for its human pasteurized C1-INH concentrate, covering the 26-year period from 1985 until 31 December 2010. RESULTS: During the reporting period, human pasteurized C1-INH concentrate representing more than 550,000 treatments was distributed. A total of 101 cases of suspected ADRs were reported worldwide, with 62 cases covered by the product's known safety profile: allergic- or anaphylactic-type reactions (11; in very rare cases involving shock), chills and fever (4), lack of effect (26), suspected virus transmission (6; not attributed to the product), and thrombosis (16). Only 2 cases of thrombosis occurred when the product was used in the labelled indication; causality was assessed as unlikely in both cases (pre-existing cerebromalacia in 1 patient, and unspecified underlying pro-thrombotic condition in a second patient with morbid obesity). The other 14 cases of thrombosis occurred during off-label use of the product (substantially higher doses than indicated). Three reports were no ADRs (product exposure during pregnancy, administration failure). Of 36 cases involving isolated reports of varying symptoms not covered by the known product safety profile, causality to the product was established for only 1 case (lightheadedness and dizziness). According to the Council for International Organizations of Medical Sciences criteria, the overall ADR reporting rate for human pasteurized C1-INH concentrate is “rare”. CONCLUSIONS: Human pasteurized C1-INH concentrate has a well-established safety profile based on 26 years of post-marketing experience with more than 550,000 treatments. The product is safe and well tolerated when used at the recommended dosage in the treatment of acute HAE attacks.