Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant)

doi:10.1016/j.jaci.2007.02.012

Journal of Allergy and Clinical Immunology

Volume 119, Issue 6, June 2007, Pages 1497-1503

https://doi.org/10.1016/j.jaci.2007.02.012 Get rights and content

Background

In hereditary angioedema, bradykinin is assumed to be the most important mediator of edema formation.

Objective

To assess whether the selective bradykinin receptor-2 antagonist Icatibant is effective in acute edema attacks of hereditary angioedema.

Methods

In this uncontrolled pilot study, 15 patients with 20 attacks were treated with Icatibant. The attacks were analyzed by using a standardized and validated visual analog scale measurement and compared with historical data of untreated attacks. Plasma bradykinin concentration was measured before and 4 hours after intravenous Icatibant treatment.

Results

Symptom intensity decreased within 4 hours after administration of Icatibant; the median time to onset of symptom relief was 1.50, 1.42, and 1.13 hours in the intravenous groups and 0.58 and 0.45 hours in the subcutaneous groups, respectively. The median difference in the 10-cm visual analog scale 4 hours after start of treatment was 4.11 cm (95% CI, 1.72-6.07). Compared with untreated attacks, Icatibant treatment reduced the mean (SD) time to onset of symptom relief by 97% from 42 ± 14 to 1.16 ± 0.95 hours (all groups combined). Median bradykinin concentration was 7-fold above the norm during acute attacks at 48.5 pmol/L and decreased to 18.0 pmol/L 4 hours after Icatibant infusion or injection.

Conclusion

Icatibant was effective in treating acute attacks of hereditary angioedema.

Clinical implications

This is the first report demonstrating the clinical usefulness of antagonizing bradykinin binding to bradykinin receptor-2 in hereditary angioedema.

Section snippets

Study design

We performed an uncontrolled pilot study to assess the efficacy of Icatibant. The design was composed of a 5 sequential group study in which the study drug Icatibant was administered either as a single i.v. infusion or a single s.c. injection. Each group consisted of 4 patients. Group I received 0.4 mg/kg body weight Icatibant administered i.v. over a period of 2 hours. Group II received the same dose infused over a period of 0.5 hours. Group III received 0.8 mg/kg over a period of 0.5 hours.

Results

Patient characteristics are summarized in Table II. The median number of attacks was 20 per year. None of the patients received angiotensin-converting enzyme inhibitors, oral contraceptives, or estrogen replacement therapy. Five patients received prophylactic long-term treatment with danazol or treatment with C1-INH concentrate. Nevertheless, these individuals still had angioedema attacks and therefore could be included in this study.

Treatment with Icatibant (Table I) resulted in a median time

Discussion

Current treatment of patients with HAE includes long-term prophylaxis and treatment of acute edema attacks.25, 26 Long-term prophylaxis with attenuated androgens (mainly danazol and stanozolol) is effective in many patients. However, a number of side effects were reported, including virilization in females, weight gain, and even liver cell adenoma and carcinoma.27, 28, 29 Although attenuated androgens reduce the total number and the severity of attacks considerably in most patients, use in

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: Disclosure of potential conflict of interest: K. Bork and P. Schlattmann have received grant support from Jerini AG. J. Nussberger has consulting arrangements with and has received grant support from Jerini AG. The rest of the authors have declared that they have no conflict of interest.

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Food allergy, anaphylaxis, dermatology, and drug allergyTreatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant)

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Study design

Results

Discussion

Immunobiology

Lancet

J Allergy Clin Immunol

Biochem Biophys Res Commun

Am J Med

Tranfus Apheresis Sci

Mayo Clin Proc

Lancet

J Allergy Clin Immunol

Emerg Med

Am J Emerg Med

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

J Hepatol

J Allergy Clin Immunol

Immunopharmacology

Food allergy, anaphylaxis, dermatology, and drug allergy
Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant)