C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks - final results of the I.M.P.A.C.T.2 study

Abstract

To cite this article: Craig TJ, Bewtra AK, Bahna SL, Hurewitz D, Schneider LC, Levy RJ, Moy JN, Offenberger J, Jacobson KW, Yang WH, Eidelman F, Janss G, Packer FR, Rojavin MA, Machnig T, Keinecke H‐O, Wasserman RL. C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks – final results of the I.M.P.A.C.T.2 study. Allergy 2011; 66: 1604–1611. Abstract Background: The placebo‐controlled study International Multicentre Prospective Angioedema C1‐INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1‐INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. Methods: I.M.P.A.C.T.2 was an open‐label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long‐term treatment with 20 U/kg C1‐INH for successive HAE attacks at any body location. Efficacy outcomes included patient‐reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per‐patient and per‐attack basis. Safety assessments included adverse events, vital signs, viral safety and anti‐C1‐INH antibodies. Results: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10–53 years of age). In the per‐patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39–0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8–26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti‐C1‐INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment‐related safety concerns. No inhibitory anti‐C1‐INH antibodies were detected in any patient. Conclusions: A single dose of 20 U/kg C1‐INH concentrate is safe and provides reliable efficacy in the long‐term treatment of successive HAE attacks at any body location. See Special Feature Page for this article http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1398-9995/homepage/free_articles.htm

New therapeutics and drugs available in Turkey

“…Herhangi bir önemli istenmeyen etki ile karşılaşılmamış ve hiçbir hastada sonraki kullanımları engelleyecek bir antikor gelişimi belirlenmemiştir. [36] Tek seferde 20 IU/kg doz uygulamasının hem etkili hem de güvenli olduğu kanıtlanmıştır.…”

Efficacy of C1 esterase inhibitor concentrate in treatment of cutaneous attacks of hereditary angioedema

“…All data for the historical controls were collected between 1976 and 2007 at the Angioedema Outpatient Service, University Hospital, Mainz, Germany, and were stored in a hospital data base. Further details of the methods and results from patients in each group are described by Craig et al 10 and Bork et al…”

“…Two patient groups were compared in this study: an active treatment group of patients who were treated for successive cutaneous attacks with 20 IU/kg of C1-INH concentrate (Berinert; CSL Behring, Marburg, Germany) in the open-label, uncontrolled I.M.P.A.C.T.2 study 10 and a group of historical control patients who had cutaneous attacks that were not treated and were part of an earlier study (Bork et al 2 ). Patients in the active treatment group were treated with a single intravenous dose of 20 IU/kg of C1-INH concentrate for each successive cutaneous attack.…”

“…However, the use of historical data to make comparisons has some unavoidable shortcomings, including differences in methodology between I.M.P.A.C.T.2 10 and Bork et al 2 and the inability to randomize patients into study groups, which would minimize or eliminate potential bias. Some demographic characteristics (age [all attack types], HAE type [facial attack subset only], and sex [facial attack subset only]) did differ between treated and untreated groups; however, a subgroup analysis of I.M.P.A.C.T.2 data revealed no clinically relevant or consistent indications that suggested that sex, age, or HAE type would have an effect on efficacy.…”

“…2,10,11,[15][16][17][18][19] In the randomized, placebo-controlled, parallel-group International Multicenter Prospective Angioedema C1-INH Trial (I.M.P.A.C.T.1) study in which single abdominal attacks or facial cutaneous attacks were treated, 20 IU/kg was established as an effective dose of C1-INH concentrate. 11 In I.M.P.A.C.T.1, the average time to symptom relief for The objective of the current analysis was to assess the efficacy of 20 IU/kg of C1-INH concentrate for treatment of acute cutaneous attacks (including facial and peripheral attacks) by comparing data from I.M.P.A.C.T.2 patients with historical data on untreated cutaneous attacks.…”