Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks

Background: C1 esterase inhibitor (C1-INH) concentrate is well established as effective therapy for hereditary angioedema (HAE). It is thought that treatment of an acute HAE attack with C1-INH as early as possible improves efficacy, but there are limited data from prospective studies supporting this recommendation.

Objective: To assess the effect of time to treatment (<6 vs ≥6 hours after start of an attack) with 20 U/kg of C1-INH concentrate on efficacy.

Methods: A post hoc analysis of time to treatment after start of an attack was performed for 2 studies with C1-INH concentrate: International Multicenter Prospective Angioedema C1-INH Trial (IMPACT) 1 (randomized, placebo-controlled) and IMPACT 2 (open-label, uncontrolled extension). Because of differences in study design, the data sets were analyzed separately. IMPACT 1 data were analyzed using Cox regression with hazard ratios (HRs). For IMPACT 2 data, linear regression was applied to evaluate whether earlier treatment leads to faster recovery. Descriptive statistics for treatment response were calculated for both studies.

Results: In IMPACT 1, treatment with C1-INH within less than 6 hours after start of an attack resulted in considerably shorter times to onset of symptom relief (HR, 3.36) and complete resolution (HR, 4.30) vs placebo. The benefit of C1-INH compared with placebo was reduced when administered after 6 or more hours (HRs, 1.18 for times to onset of symptom relief and 1.61 for complete resolution). Analysis of IMPACT 2 data indicated slower complete resolution of symptoms with later start of treatment.

Conclusion: Early treatment with C1-INH (<6 hours) provides a better treatment response than late treatment (≥6 hours), supporting the international recommendation to treat HAE attacks as early as possible.

Trial registration: ClinicalTrials.gov Identifiers: NCT00168103 and NCT00292981.