Hereditary angioedema (HAE) is a heterozygous deficiency of first component of complement-inhibitor (C1INH). Insufficient C1INH activity leads to uncontrolled activation of plasma cascade systems, which results in acute angioedema attacks in patients with HAE. Plasma-derived or recombinant C1INH products are approved for the treatment of such angioedema attacks. The target level of C1INH activity needed to achieve optimal efficacy, however, remains unknown. We determined the plasma level of C1INH associated with optimal clinical efficacy in the treatment of angioedema attacks. Efficacy and pharmacokinetic data were reviewed from recently published placebo-controlled randomized trials in the treatment of HAE with either plasma-derived or recombinant C1INH products, tested at various doses. A dose-dependent effect was observed on time to the beginning of relief of symptoms, on time to resolution of symptoms, and on the response rate within 4 h. Optimal efficacy of C1INH therapy is achieved at doses ≥50 U/kg. This dose increases plasma C1INH activity in almost all patients to values ≥0.7 U/ml (70% of normal), the lower limit of the normal range. The differences in half-lives of the various C1INH products do not have an obvious effect on clinical efficacy. A review of the efficacy and pharmacokinetic data from recently published controlled studies in the treatment of HAE attacks suggests that efficacy of C1INH therapy is optimal when C1INH activity levels are restored to the normal range.
