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.)
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.
The differential diagnostic work-up of children with chronic eczema should involve patch testing, also in cases with confirmed atopy. In our previous study, contact allergy was detected in every second child with chronic eczema. The aim of the present study was to identify the most important sensitizers in atopic children with eczema. During an allergy screening program, 103 consecutive children aged 7-8 and 93 adolescents aged 16-17 were enrolled. The inclusion criterion was chronic recurrent eczema as detected with the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and atopy, defined as positive skin prick test to one or more common airborne or food allergens. The children were patch-tested with the newly extended European Baseline Series (EBS, 28 test substances) supplemented with propolis, thimerosal, benzalkonium chloride, and 2-phenoxyethanol. In total, 67.0% children and 58.1% adolescents were found patch test positive. Among children, 35.9% reacted to nickel, 16.5% propolis, 11.7% thimerosal, 9.7% cobalt, each 6.8% fragrance mix (FM) I and chromium, and 5.8% to FM II. Among adolescents, 37.6% reacted to thimerosal, 19.4% to nickel, 6.5% to cobalt, and 5.4% to propolis. We demonstrate the advantage of using FM II - a new addition to the EBS that detects a relatively high proportion of contact hypersensitivity among children. An important sensitizer from outside EBS is propolis, which according to the frequency of sensitization occupies rank 2 in children and rank 4 in adolescents. These data show that propolis should be included into routine patch testing in children.
The transgenically produced rHuC1INH was successfully used in the treatment of acute angioedema attacks in patients with hereditary C1-inhibitor deficiency.
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