BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P = 0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)

C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.

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

No abstract

No abstract

No abstract

No abstract