Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) who are treated with long-term prophylaxis (LTP) have similar rates of acute attacks as patients who are not treated with LTP. A single subcutaneous injection of icatibant was effective for treating more than 80% of all attacks. These study results were published in Allergy, Asthma & Clinical Immunology.

In HAE, C1-inhibitor deficiency or dysfunction results in bradykinin overproduction, bradykinin B2 receptor activation, capillary leakage, and local edema, leading to recurrent attacks of cutaneous or submucosal edema.

Patients with C1-INH-HAE are advised have ready access to “on-demand treatment” for acute angioedema attacks. Some patients may be treated with LTP to lower the risk and severity of recurrent attacks. However, breakthrough attacks — sometimes severe — have been known to occur in patients receiving LTP. Data are lacking regarding the characteristics and treatment of breakthrough attacks during LTP.


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Icatibant (Firazyr®; Shire; Zug Switzerland) is a subcutaneous bradykinin B2 receptor antagonist indicated to treat acute angioedema attacks in adults with type 1 (C1-inhibitor deficiency) or type 2 (C1-inhibitor dysfunction) C1-INH-HAE. The Icatibant Outcome Survey (IOS; ClinicalTrials.gov identifier: NCT01034969) is an observational study evaluating the effectiveness and safety of icatibant in clinical practice.

Researchers from the IOS Study Group compared the characteristics of breakthrough attacks on LTP vs not on LTP and evaluated icatibant as a treatment for acute attacks in patients with C1-INH-HAE.

A total of 3228 attacks treated with icatibant occurred in 448 patients. Nearly all (94.4%) patients had C1-INH-HAE type 1.

Rates of icatibant-treated attacks were similar between patients receiving LTP and patients not receiving LTP at the time of the attack. Approximately one-third of attacks occurred in 171 patients on LTP (38.2%), and 69.9% attacks occurred in 323 patients (72.1%) who had never received LTP or were not on LTP at the time of the attack.

Androgens, tranexamic acid, and C1-INH alone or in combination were used as LTP. Attacks rates were similar regardless of the LTP regimen used and LTP status.

No differences in attack severity were found between no LTP vs LTP with androgens (P =.056), tranexamic acid (P =.989), or C1-INH (P =.321).

The majority of attacks were successfully treated with a single injection of icatibant in both the LTP (82.5%) and no LTP (82.8%) groups. More than 1 icatibant injection was required in 9.6% and 8.4% of attacks in patients with LTP vs without LTP, and 9.8% in both groups needed additional C1-INH rescue medication.

Approximately half of all attacks involved the abdomen and approximately 5% involved the larynx in both groups. Rates of severe to very severe attacks were 73.9% and 63.6% in the abdomen and larynx, respectively.

Attack duration, time to treatment with icatibant, and time to attack resolution were similar between the LTP and no LTP groups.

“Our findings show that icatibant, when used as on-demand medication, is similarly effective in controlling attacks in patients who are taking LTP and in those who are not,” the researchers wrote.

“Patients who are prescribed LTP should be aware of the potential for breakthrough attacks, including those of high severity and involving the larynx, and should be prepared by having easily accessible emergency treatment,” they added.

Disclosures: The researchers report financial relationships with CSL Behring, Pharming, Shire, Dyax, Novartis, GlaxoSmithKline, Roche, and SOBI. Several researchers are employees of Shire.

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Reference

Aberer W, Maurer M, Bouillet L, et al; for the IOS Study Group. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant: findings from the Icatibant Outcome Survey. Allergy Asthma Clin Immunol. 2017;13:31. doi:10.1186/s13223-017-0203-z