Efficacy and Safety of Long-Term Prophylaxis with C1 Inhibitor (C1INH) Concentrate in Patients with Hereditary Angioedema (HAE)

C1INH is widely recognized to be the most effective treatment for acute attacks of HAE. With its relatively long half-life, C1INH may also be effective for long-term prophylaxis. This study, therefore, addressed the impact of long-term prophylactic C1INH on HAE swelling frequency. This multi-center study enrolled 22 patients meeting diagnostic criteria for HAE plus a history of at least 2 attacks per month. Subjects were randomized to receive 12 weeks of either C1 inhibitor (Cinryze, Lev Pharmaceuticals) 1000 units 2×/week or placebo (normal saline) 2×/week by intravenous infusion. At the end of 12 weeks all subjects were crossed over. No changes in other prophylactic medications (androgens or antifibrinolytics) was permitted during the entire 24 weeks or the preceding 4 weeks. The number of discrete angioedema attacks and days of swelling during each arm of the study were summed, and the primary endpoint was the number of attacks on C1 inhibitor versus number of attacks on placebo using each subject as his/her own control. The number of attacks during the C1INH treatment phase was significantly less than during the placebo treatment phase (6.1 vs 12.7, p < 0.0001). Secondary endpoints, including days of swelling (10.1 vs 29.6) also showed a significant benefit for the C1INH phase (p < 0.0001). No safety issues were identified. Prophylactic infusion with C1INH decreases the number of attacks experienced by patients with active HAE and may represent an important modality of treatment for some patients.