Safety of C1-esterase inhibitor in acute and prophylactic therapy of hereditary angioedema: findings from the ongoing international Berinert patient registry.

BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typically with off-label use or at supratherapeutic doses. OBJECTIVES: Active surveillance of safety and clinical usage patterns of pasteurized C1-inhibitor concentrate and the more recent pasteurized, nanofiltered C1-INH, with a particular interest in thromboembolic events. METHODS: A registry was initiated in April 2010 at 27 US and 4 EU sites to obtain both prospective and retrospective safety and usage data on subjects who were administered C1-INH (Berinert). RESULTS: As of May 10, 2013, data were available for 135 subjects and 3196 infusions. By subject, 67.4% were using C1-INH as on-demand therapy and 23.0% as both on-demand therapy and prophylactic administration. Approximately half of the infusions (49.5%) were administered for prophylaxis and >90% were given by the patient or a caregiver in the home setting. A total of 299 adverse events were reported, for an overall rate of 0.09 events per infusion with only 6 considered related to C1-INH. Two thromboembolic events were reported, both in patients with prothrombotic risk factors. CONCLUSION: This large pool of real-world clinical usage data in HAE further supports the extensive safety profile of 2 Berinert formulations when used on demand and/or for prophylaxis in both home and health care settings. No evidence was found to suggest that Berinert is an independent, causative risk factor for thromboembolic events.