Summary:C1 esterase inhibitor (C1-INH) concentrates are effective for the treatment of attacks (on-demand treatment) and the prophylaxis (short- and long-term) of hereditary angioedema (HAE). Patients with HAE lack functional C1-INH, resulting in excessive activation of the complement system (with resulting reduced C4 serum levels), as well as overproduction of bradykinin (responsible for the capillary permeability and angioedema). Replacement with exogenous C1-INH restores normal C1-INH functional activity.
Two C1-INH concentrates are derived from human plasma, following pasteurization and nanofiltration: Berinert and Cinryze. Berinert is approved in adults and children for the on-demand treatment of HAE attacks in Germany and Europe (since 1979), in the USA (since 2009), and in Canada (since 2010). Berinert is licensed for self-administration intravenously at home. Cinryze is approved in adults and adolescents for the on-demand treatment and prophylaxis (short- and long-term) of HAE attacks in Germany and Europe (since 2011), although in the USA, it is approved for the long-term prophylaxis of HAE attacks (since 2008). Cinryze is self-administered intravenously every 3-4 days. Of note, Cetor is a similar product, approved in the European Union for acute attacks, but is not approved by the FDA in the U.S.
One recombinant C1-INH is currently available: Ruconest (previously, Rhucin). The product is obtained from the milk of transgenic rabbits (i.e. the human C1INH gene is introduced into fertilized rabbit oocytes in a mammary-gland-specific expression vector). Ruconest is approved in adults and adolescents for the on-demand treatment of HAE attacks in Europe (since 2010) and USA (since 2014). It is self-administered intravenously.
Significant safety concerns that have been reported include:
- Hypersensitivity reactions (including anaphylaxis);
- Thrombotic events (arterial and venous).
- Others: headache, nausea, diarrhea. As this is a blood product, there is also the theoretical risk of transmission of an infectious agent.