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

Timothy J. Craig, Mikhail A. Rojavin, Thomas Machnig, Heinz Otto Keinecke, Jonathan A. Bernstein

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)211-215
Number of pages5
JournalAnnals of Allergy, Asthma and Immunology
Issue number3
StatePublished - Sep 2013

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine


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